Optimal intensity for respiratory muscle endurance training in patients with spinal cord injury.

OBJECTIVE: Respiratory muscle endurance of able-bodied persons, assessed by normocapnic hyperpnoea at 70% of their maximal voluntary ventilation, usually ranges from 10 to 20 minutes. The aim of this study was to determine the level of ventilation that patients with paraplegia and tetraplegia can sustain for 10-20 minutes to later be used as the guideline for respiratory muscle endurance training. DESIGN: Pilot study; cross-over setting. SUBJECTS: Two groups, 8 patients with paraplegia and 6 with tetraplegia. METHODS: Respiratory muscle endurance tests were performed at 3 different intensities of normocapnic hyperpnoea, i.e. 20%, 40% and 60% maximal voluntary ventilation. Subjects performed partial re-breathing from a bag to assure normocapnia. Respiratory endurance was separately analysed for patients with paraplegia and tetraplegia. RESULTS: Mean respiratory endurance times were 46.0, 18.9 and 4.2 minutes at 20%, 40% and 60% maximal voluntary ventilation in patients with tetraplegia and 51.8, 38.8 and 12.2 minutes in patients with paraplegia. The duration differed significantly at 60% maximal voluntary ventilation between the groups. CONCLUSION: Minute ventilation to perform respiratory muscle endurance training can be set at around 40% of maximal voluntary ventilation for patients with tetraplegia and around 60% of maximal voluntary ventilation for patients with paraplegia, as these levels can be sustained for 10-20 minutes.     

Basal and metoclopramide-stimulated prolactin (PRL) serum levels in users and non-users of a copper intrauterine device (TCu-380 IUD).

The study was undertaken to analyze the basal and metoclopramide-stimulated serum PRL levels in healthy parous women users (group 1, n = 12) and non-users (group 2, n = 12) of a TCu-380 IUD. All women had regular menses and were studied between days 18 to 22 of their cycle; none had lactated nor regularly ingested any type of medication during the last six months. After a 10-12 hour overnight fast, peripheral venous blood samples were obtained through an indwelling catheter at -30, -15 and 0 minutes and at 60, 90 and 120 minutes after oral metoclopramide (10 mg). There were no significant differences in serum PRL between both groups, in basal levels nor throughout the test, whether analyzing the mean values at each sampling time, the sum of PRL levels from 60-120 minutes, or the peak levels. No correlation was observed between PRL levels and any of the clinical or obstetric characteristics of the women in both groups. Serum progesterone was greater than or equal to 4.0 ng/ml in all women. Thus, the use of alpha TCu-380 IUD did not induce any significant changes in basal nor in stimulated serum PRL levels.     

Functional and morphological changes in diabetic macular edema over the course of anti‐vascular endothelial growth factor treatment

Purpose:  To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti‐vascular endothelial growth factor (VEGF) treatment with Ranibizumab. Methods:  A consecutive series of 39 study eyes with centre‐involving DME were included in this study. In all subjects, best‐corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD‐OCT) cross‐sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross‐sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Results:  Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = ?1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = ?3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = ?4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = ?1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = ?0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = ?2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. Conclusions:  ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti‐VEGF therapy with Ranibizumab in patients with DME.     

Order of genetic events is critical determinant of aberrations in chromosome count and structure

A sequential acquisition of genetic events is critical in tumorigenesis. A key step is the attainment of infinite proliferative potential. Acquisition of this immortalization requires the activation of telomerase in addition to other activities, including inactivation of TP53 and the retinoblastoma family of tumor-suppressor proteins. However, the importance of the order in which these genetic events occur has not been established. To address this question, we used a panel of normal mammary fibroblasts and endothelial cultures that were immortalized after transduction with the catalytic subunit of telomerase (hTERT) and a temperature-sensitive mutant of the SV40 large-tumor (tsLT) oncoprotein in different orders in early- and late-passage stocks. These lines were maintained in continuous culture for up to 90 passages, equivalent to >300 population doublings (PDs) post-explantation during 3 years of continuous propagation. We karyotyped the cultures at different passages. Cultures that received hTERT first followed by tsLT maintained a near-diploid karyotype for more than 150 PDs. However, in late-passage stocks (>200 PDs), metaphase cells were mostly aneuploid. In contrast, the reverse order of gene transduction resulted in a marked early aneuploidy and chromosomal instability, already visible after 50 PDs. These results suggest that the order of genetic mutations is a critical determinant of chromosome count and structural aberration events.     

Pain response measured with arterial spin labeling

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level‐dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed‐continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised. Copyright © 2013 John Wiley & Sons, Ltd.     

Chronic Pain and Premature Aging – The Moderating Role of Physical Exercise

Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n = 67) and without chronic pain (n = 49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was nonsignificant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain.PerspectiveThe study suggests that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular PE in this respect as it may moderate premature ageing.