Thermographic assessment of the immediate and short term-effects of blood flow restriction exercise on Achilles tendon skin temperature.

OBJECTIVES: To determine the thermal patterning of the Achilles tendon following bodyweight resistance exercise with and without blood-flow restriction (BFR). DESIGN: Cross-sectional. SETTING: Research laboratory. PARTICIPANTS: Twelve asymptomatic recreational runners (Age: 37 ± 10, Height: 169 ± 20, Mass: 73.8 ± 13.4). MAIN OUTCOME MEASURES: Thermograms were taken pre and post exercise with and without a BFR cuff on separate legs. BFR cuff pressure was set at 80% maximal arterial occlusion pressure determined using doppler via the tibial artery. Linear mixed-effects models were used to assess the effect of BFR and time post-exercise on skin-temperature (Tskin). RESULTS: A lower Tskin was seen following BFR exercise at the tendon insertion (P = 0.002), but not at the free tendon (P = 0.234), or the musculotendinous junction (P = 0.933). A significant effect of time upon changes in Tskin was observed in both BFR and non-BFR groups (P = 0.002). No interaction of time and BFR were observed on changes in Tskin (P = 0.726). CONCLUSION: Region specific changes in Tskin were found, with greater and longer reductions observed at the insertion of the Achilles following BFR exercise before returning to baseline. These findings could have implications for the programming of BFR exercise on tendon health. Future research should observe for differences between symptomatic and healthy tendons.

GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABA(A) autoreceptor/Cl- channels.

GABA emerges as a trophic signal during rat neocortical development in which it modulates proliferation of neuronal progenitors in the ventricular/subventricular zone (VZ/SVZ) and mediates radial migration of neurons from the VZ/SVZ to the cortical plate/subplate (CP/SP) region. In this study we investigated the role of GABA in the earliest phases of neuronal differentiation in the CP/SP. GABAergic-signaling components emerging during neuronal lineage progression were comprehensively characterized using flow cytometry and immunophenotyping together with physiological indicator dyes. During migration from the VZ/SVZ to the CP/SP, differentiating cortical neurons became predominantly GABAergic, and their dominant GABA(A) receptor subunit expression pattern changed from alpha4beta1gamma1 to alpha3beta3gamma2gamma3 coincident with an increasing potency of GABA on GABA(A) receptor-mediated depolarization. GABA(A) autoreceptor/Cl(-) channel activity in cultured CP/SP neurons dominated their baseline potential and indirectly their cytosolic Ca(2+) (Ca(2+)c) levels via Ca(2+) entry through L-type Ca(2+) channels. Block of this autocrine circuit at the level of GABA synthesis, GABA(A) receptor activation, intracellular Cl(-) ion homeostasis, or L-type Ca(2+) channels attenuated neurite outgrowth in most GABAergic CP/SP neurons. In the absence of autocrine GABAergic signaling, neuritogenesis could be preserved by depolarizing cells and elevating Ca(2+)c. These results reveal a morphogenic role for GABA during embryonic neocortical neuron development that involves GABA(A) autoreceptors and L-type Ca(2+) channels.

Clinical outcome of primary non-metastatic breast cancer: A single institution experience.

BACKGROUND: We report on prognostic factors and long-term survival of non-metastatic breast cancer patients treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC) in Pakistan. MATERIALS AND METHODS: This retrospective cohort study is based on a review of 2829 pathologically confirmed non-metastatic breast cancer patients managed from January 1995 to May 2009. Median age was 45 years. Stage at presentation: Stage I (9%), stage II (59%), and stage III (32%). Infiltrating ductal carcinoma (92%) constituted the most prevalent histological subtype. Estrogen (ER), progesterone (PR) and Her2-neu were positive in 49%, 50%, and 26%, respectively. A mastectomy was performed in 67% and conservative surgery in 33% of the patients. Post-operative radiotherapy was delivered in 85% of the cases. Ninety percent of the patients received chemotherapy and mainly consisted of anthracycline-based regimens + taxanes. Hormonal manipulation was done in ER/PR positive patients. RESULTS: The 5- and 10-year overall survival (OS) was 70% (95% confidence interval [CI]: 68.2-71.8%) and 54% (95%CI: 51.2-56.8%), while disease free survival (DFS) was 65% (95% CI: 63-67%) and 52% (95% CI: 49.2-54.8%), respectively. Recurrence following primary treatment was seen in 35% of the patients. On multivariate analysis T stage, number of axillary nodal involvement, tumor grade, ER status and family history, were found to be independent predictors for OS and DFS. CONCLUSIONS: Over 90% of non-metastatic breast cancer patients present with stagesII and III disease and a significant proportion develop distant metastasis accounting for overall long-term outcome inferior to developed countries. Efforts should be directed to raise the level of health awareness and screening programs to improve early detection in Pakistan.

Response variability in the visual field: comparison of optic neuritis, glaucoma, ocular hypertension, and normal eyes.

PURPOSE: To compare the relationship between sensitivity and response variability in the visual field of normal eyes and eyes with optic neuritis (ON), glaucoma (POAG), and ocular hypertension (OHT). METHODS: Frequency-of-seeing (FOS) data were collected from four visual field locations in one eye of 71 subjects (12 ON, 25 POAG, 11 OHT, and 23 normal), using a constant stimulus method on an Henson 4000 perimeter (Tinsley Instruments, Croydon, UK). At each location, at least 20 stimuli (subtending 0.5 degrees) were presented for 200 ms at six or more intensities above and below the estimated threshold. The mean and SD of the probit fitted cumulative Normal function were used to estimate sensitivity and response variability. Cluster regression analysis was carried out to determine whether there were differences in the sensitivity-log (variability) relationship between the four groups. RESULTS: Variability was found to increase with decreased sensitivity for all four groups. The combined data from the four groups was well represented (R2 = 0.57) by the function log(e)(SD) = A.sensitivity (dB) + B, where the constants A and B were -0.081 (SE, +/-0.005) and 3.27 (SE, +/-0.15), respectively. Including other statistically significant covariates (false-negative errors, P = 0.004) and factors (diagnosis, P = 0.005) into the model increased the proportion of explained variance to 62% (R2 = 0.62). Stimulus eccentricity (P = 0.34), patient age (P = 0.33), fixation loss rate (P = 0.10), and false-positive rate (P = 0.66) did not reach statistical significance as additional predictors of response variability. CONCLUSIONS: The relationship between response variability and sensitivity is similar for ON, POAG, OHT, and normal eyes. These results provide supporting evidence for the hypothesis that response variability is dependent on functional ganglion cell density.

The direct determination of aldosterone in human saliva.

A method is described for the direct radioimmunoassay of aldosterone in human saliva without preliminary extraction or chromatographic purification. The method has been validated with respect to sensitivity, accuracy, precision, specificity and other criteria. Under basal conditions concentrations of aldosterone in saliva ranged from 10-63% those of plasma (mean +/- SD = 32.5 +/- 13.1%). When plasma aldosterone responded to such acute stimuli as postural change, exercise or ACTH infusion, this was promptly reflected in corresponding changes in saliva aldosterone concentration. In subjects going about their normal daily business saliva aldosterone concentration fluctuated markedly during the day. It is therefore difficult to define a normal range for saliva aldosterone concentration but present observations suggest an upper limit of 150 pmol/l under basal conditions.

Modulation of smooth muscle phenotype in vitro by homologous cell substrate.

We have developed a novel cell culture system that supports the shortening of smooth muscle cells. Primary rat airway smooth muscle cells were plated on an ethanol-fixed, confluent monolayer of homologous smooth muscle cells (homologous cell substrate, HCS). Cells grown on HCS exhibited morphological and functional characteristics consistent with a differentiated phenotype. Cells on HCS were spindle shaped with a well-defined long axis, whereas cells grown on glass were larger and irregularly shaped. Smooth muscle-specific alpha-actin immunostained diffusely in cells on HCS, whereas it appeared as stress fibers in cells on glass. Agonists recruited a greater fraction of HCS cells to contract, resulting in greater changes in cell area or length on average, but the maximal capacity of shortening of individual cells was similar between the groups. Unlike cells on glass, cells on HCS shortened to methacholine. HCS was reversible and persisted over several passages. Agonists stimulated intracellular Ca(2+) oscillations in cells on HCS, whereas they elicited biphasic peak and plateau transients in cells on glass. HCS modulates smooth muscle cell phenotype in vitro.