Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine.

BACKGROUND: A subset of patients with postural tachycardia syndrome (POTS) are thought to have a primary hyperadrenergic cause. We assessed clinical biomarkers to identify those that would benefit from sympatholytic therapy. METHODS: We measured sympathetic function (supine muscle sympathetic nerve activity, upright plasma norepinephrine, and blood pressure responses to the Valsalva maneuver) in 28 patients with POTS (phenotyping cohort) to identify clinical biomarkers that are associated with responsiveness to the central sympatholytic guanfacine in a separate uncontrolled treatment cohort of 38 patients that had received guanfacine clinically for suspected hyperadrenergic POTS (HyperPOTS). RESULTS: In the phenotyping cohort, an increase in diastolic blood pressure (DBP) >17 mm Hg during late phase 2 of the Valsalva maneuver identified patients with the highest quartile of resting muscle sympathetic nerve activity (HyperPOTS) with 71% sensitivity and 85% specificity. In the treatment cohort, patients with HyperPOTS, identified by this clinical biomarker, more often reported clinical improvement (85% versus 44% in nonhyperadrenergic; P=0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: -1.9±0.9 versus 0.1±0.5; P=0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: -12.9±2.7 versus -2.2±2.2; P=0.005) in response to guanfacine. CONCLUSIONS: These results are consistent with the concept that POTS is caused by a central sympathetic activation in a subset of patients, which can be identified clinically by an exaggerated DBP increase during phase 2 of the Valsalva maneuver and improved by central sympatholytic therapy. These results support further clinical trials to determine the safety and efficacy of guanfacine in patients with POTS enriched for the presence of this clinical biomarker.

[What's new in diabetic retinopathy ?] / Actualités dans la rétinopathie diabétique.

Diabetic retinopathy is a public health issue and the leading cause of blindness in adults in industrialized countries. Many advances have been made during the last few years in the diagnosis, the understanding of the pathophysiology and the treatment of diabetic retinopathy, especially with the rise of anti-angiogenic treatments. We bring here an overview of the last advances, the current therapeutic algorithms and future perspectives.

La rétinopathie diabétique est un problème de santé publique et est la première cause mondiale de cécité dans les pays industrialisés. Les dernières années ont été marquées par des progrès dans le diagnostic, la compréhension de la physiopathologie et le traitement de la rétinopathie diabétique, notamment avec l'introduction des traitements visant à réduire l'angiogenèse rétinienne. Cet article passe en revue les dernières avancées dans ces domaines, l'algorithme thérapeutique appliqué actuellement et les perspectives futures.

How we improve the transoral resection for oral and oropharyngeal cancer: the CO2 waveguide laser.

PURPOSE: The main aim of this study was to evaluate the CO2 waveguide laser (CO2 WGL) with flexible fiber (Lumenis, Santa Clara, CA) in the treatment of oral and oropharyngeal cancers specifically focusing on the lateral thermal damage (LTD) induced by this instrument and therefore on the reliability of the analysis of frozen sections collected during margin mapping. METHODS: A total of 48 patients with oral and oropharyngeal cancers from T1 to T4a were prospectively enrolled in the study. We collected data about LTD, pathologic tumor and node stage (pTNM), surgical intervention, kind of reconstruction (no flap, local vs free flap), need for tracheotomy and time of removal, postoperative complications (such as bleeding, mucosal dehiscence, and fistula), need for feeding tube and time of removal. RESULTS: Mean LTD was 164.7 ± 92.4 µm. Comparing frozen section histology before and after formalin embedding we found 5 true positives, 170 true negatives, 4 false positives and 4 false negatives, with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 55.6%, 98%, 55.6%, 98%, and 96.1%, respectively. CONCLUSION: CO2 WGL is a very manageable tool, which allows a precise cut. However, its high costs, the inability to re-use the fibers and its low coagulation capability must be considered.

Saccades and smooth pursuit eye movements in central vertigo.

In order to analyze the diagnostic efficiency of saccadic and pursuit eye movements compared to findings from brain magnetic resonance imaging in patients with central vertigo, 108 patients were selected from 580 dizzy patients as cases of suspected central origin; the saccadic and pursuit eye movements were evaluated by electronystagmography and findings were compared to information from magnetic resonance imaging. The study of oculomotor movements in patients suspected of having a central lesion revealed a 83.3% sensitivity and 21.2% specificity. Restricting consideration to severe alterations in eye movements as indicative of a central origin, this test gives a 71.4% sensitivity and 50.0% specificity. In conclusion, the study of alterations in oculomotor movements, in patients with suspected central lesions, proved to be a test with good sensitivity also compared with results of magnetic resonance imaging.

Specific block of androgen receptor activity by antisense oligonucleotides.

Claims about molecular mechanisms underlying the resistance to anti-hormones of prostate cancer cells find support in biological experiments, which involve hormone-independent activation of the androgen receptor's (AR) transcriptional activity. In order to test this hypothesis, we attempted to shut down the expression of AR by the means of target-directed antisense oligonucleotides. A set of 49 oligonucleotides matching sequences of the AR mRNA either in the coding sequence or in the 3' and 5' untranslated regions were synthesized and examined in a cellular AR-dependent reporter system. Five antisense oligonucleotides were identified as highly potent inhibitors of AR-driven gene expression in a cellular reporter assay. These five were further profiled using point-mutated control sequences for the assessment of AR inhibition. In addition the expression of another AR-driven gene, the modulator of PSA expression (gene for inhibition of prostate specific antigen, an endogenous, AR-driven gene) was examined. Finally, we observed that the hormone-independent but AR-mediated transactivation by IGF-1 could also be specifically shut-down by these antisense oligonucleotides. The selection of highly target-restricted antisense oligonucleotides in the prostate cancer cell line LNCaP provided tools to study a central role of the androgen receptor in growth regulation of prostatic cancer cell lines and could be of utility in cancer situations in vivo.

Limiting step involved in the thermal growth of silicon oxide films on silicon carbide.

Thermal growth of silicon oxide films on silicon carbide in O2 was investigated using oxygen isotopic substitution and narrow resonance nuclear reaction profiling. This investigation was carried out in parallel with the thermal growth of silicon oxide films on Si. Results demonstrate that the limiting steps of the thermal oxide growth are different in these two semiconductors, being diffusion limited in the case of Si and reaction limited in the case of SiC. This fact renders the growth kinetics of SiO2 on SiC very sensitive to the reactivity of the interface region, whose compositional and structural changes can affect the electrical properties of the structure.

Keratinolysis and its morphological expression in hair digestion by airborne fungi.

The morphological expression of keratinolysis in fungi isolated from the air of Torino (98 isolates belonging to 36 species) was studied. Light microscopy on whole material and on semithin sections, as well as scanning electron microscopy was used. There were 19 keratinolytically active species, with seven in the genus Chrysosporium (C. indicum, C. keratinophilum, C. pannicola, C. tropicum, C. an. Arthroderma cuniculi, C. an. Pectinotrichum llanense, C. an. Renispora flavissima), four in the genus Malbranchea (M. arcuata, M. fulva, M. sulphurea, M. st. Uncinocarpus reesii), and three in the genus Trichophyton (T. mentagrophytes, T. rubrum, T. terrestre). In addition there were Aphanoascus fulvescens, Beauveria bassiana, Geomyces pannorum v. pannorum, Gymnoascus umbrinus and Myceliophthora vellerea. Most of these species were capable of developing structures related to surface erosion and radial penetration contemporaneously. However Gymnoascus umbrinus, Myceliophthora vellerea, an isolate of C. indicum, C. tropicum and Trichophyton mentagrophytes demonstrated only surface erosion. Different isolates of one species can vary in their production of invasive structures and in degree of keratinolytic activity. Thus such activity, like many biochemical activities of fungi, does not appear to be a constant or rigorously species-specific character.