A hypothetical proposal for association between migraine and Meniere's disease.

Meniere's disease (MD) is a chronic condition affecting the inner ear whose precise etiology is currently unknown. We propose the hypothesis that MD is a migraine-related phenomenon which may have implications for future treatment options for both diseases. The association between MD and migraine is both an epidemiological and a mechanistic one, with up to 51% of individuals with MD experiencing migraine compared to 12% in the general population. The presence of endolymphatic hydrops in those with MD may be the factor that unites the two conditions, as hydropic inner ears have an impaired ability to maintain homeostasis. Migraine headaches are theorized to cause aura and symptoms via spreading cortical depression that ultimately results in substance P release, alterations in blood flow, and neurogenic inflammation. Chronically hydropic inner ears are less able to auto-regulate against the changes induced by active migraine attacks and may ultimately manifest as MD. This same vulnerability to derangements in homeostasis may also explain the common triggering factors of both MD attacks and migraine headaches, including stress, weather, and diet. Similarly, it may explain the efficacy of common treatments for both diseases: current migraine treatments such as anti-hypertensives and anti-convulsants have shown promise in managing MD. Though the etiology of both MD and migraine is likely multifactorial, further exploration of the association between the two conditions may illuminate how to best manage them in the future. MD is likely a manifestation of cochleovestibular migraine, which occurs as a result of migraine related changes in both the cochlea and vestibule

Adjuvant Migraine Medications in the Treatment of Sudden Sensorineural Hearing Loss.

Objectives/hypothesisTo examine the hearing outcomes of patients with sudden sensorineural hearing loss (SSNHL) treated with oral and intratympanic (IT) steroid only or a combination of steroid and migraine treatment. Our hypothesis was that adjuvant migraine medications may improve outcomes in SSNHL.MethodsA retrospective chart review at a tertiary otology center was conducted to identify patients with SSNHL who received oral steroid and IT dexamethasone injection(s) with or without migraine medications (a combination of nortriptyline and topiramate).ResultsA total of 47 patients received oral steroid and IT dexamethasone injection(s) only, and 46 patients received oral steroid and IT dexamethasone injection(s) as well as migraine lifestyle changes plus a combination of nortriptyline and topiramate. There were no significant differences in demographics and baseline audiometric data between the two groups. Both groups demonstrated improvements in pure tone average (PTA) and hearing thresholds at 250 Hz and 8000 Hz posttreatment. However, compared to steroid-only group, the adjuvant migraine medications group had significantly greater improvements in hearing thresholds at the lower frequencies (250 Hz, 500 Hz, 1000 Hz). Patients in the latter cohort also had greater improvement in PTA (P = .01) and received fewer IT injections (P = .04) PTA improvement of ≥ 10 dB was observed in 36 patients (78%) in the adjuvant migraine medications group and 22 patients (46%) in the control group (P < .001).ConclusionIn multimodal treatment of SSNHL, supplementing oral and IT steroid with migraine medications may result in greater improvements in lower frequency hearing thresholds and PTA. Furthermore, adjuvant migraine treatment can lead to decrease in number of IT injections, thus reducing procedure-related risks and complications.Level of evidence3 Laryngoscope, 131:E283-E288, 2021

Efficacy of Multi-Modal Migraine Prophylaxis Therapy on Hyperacusis Patients.

ObjectivesTo evaluate the efficacy of a multi-modal migraine prophylaxis therapy for patients with hyperacusis.MethodsIn a prospective cohort, patients with hyperacusis were treated with a multi-modal step-wise migraine prophylactic regimen (nortriptyline, verapamil, topiramate, or a combination thereof) as well as lifestyle and dietary modifications. Pre- and post-treatment average loudness discomfort level (LDL), hyperacusis discomfort level measured by a visual analogue scale (VAS), and scores on the modified Khalfa questionnaire for severity of hyperacusis were compared.ResultsTwenty-two of the 25 patients (88%) reported subjective resolution of their symptoms following treatment. Post-treatment audiograms showed significant improvement in average LDL from 81.3 ± 3.2 dB to 86.4 ± 2.6 dB (P < .001), indicating increased sound tolerability. The VAS discomfort level also showed significant improvement from a pre-treatment average of 7.7 ± 1.1 to 3.7 ± 1.6 post-treatment (P < .001). There was also significant improvement in the average total score on modified Khalfa questionnaire (32.2 ± 3.6 vs 22.0 ± 5.7, P < .001).ConclusionsThe majority of patients with hyperacusis demonstrated symptomatic improvement from migraine prophylaxis therapy, as indicated by self-reported and audiometric measures. Our findings indicate that, for some patients, hyperacusis may share a pathophysiologic basis with migraine disorder and may be successfully managed with multimodal migraine prophylaxis therapy

Implikasi Yuridis Legalitas Kewenangan (Rechtmatigheid) Majelis Kehormatan dalam Pembinaan Notaris sebagai Pejabat Publik

Diundangkannya UU Perubahan Atas Undang-Undang No.30 Tahun 2004 yaitu Undang Undang No.2 Tahun 2014, memunculkan lembaga baru yang disebut Majelis Kehormatan Notaris yang mempunyai tugas melaksanakan pembinaan sebagaiman diatur dalam Pasal 66A ayat (1).Disisi lain berdasarkan Pasal 1 angka (6) mengenai Majelis Pengawas Notaris disebutkan mempunyai kewenangan dan kewajiban untuk melaksanakan pembinaan dan pengawasan terhadap Notaris. Implikasi yuridis yang terjadi adalah adanya pertentangan norma antara ketentuan yang diatur dalam ketentuan Pasal 1 Angka (6), Pasal 66A dan pasal 67Undang-Undang No.2 Tahun 2014 tentang Perubahan atas Undang-Undang No.30 Tahun 2004. Dengan metode penelitian hukum normatif dengan pendekatanperundang-undangan (Statue Approach) dan Pendekatan Analisis Konsep Hukum (Analitical Conceptual Approach), penulis akan menganalisa ruang lingkup kewenangan keberadaan Majelis Pengawas Notaris dan Majelis Pengawas Notaris serta legalitas kewenangan fungsi Majelis Kehormatan Notaris dalam lembaga notariat sehingga tidak terjadi pertentangan kewenangan diantara kedua lembaga notariat tersebut

Oral contraceptive progestins and angiotensin-dependent control of the renal circulation in humans

Oral contraceptive (OC) use is associated with increased intra-renal renin-angiotensin-aldosterone system (RAA System) activity and risk of nephropathy, though the contribution of progestins contained in the OC in the regulation of angiotensin-dependent control of the renal circulation has not been elucidated. Eighteen OC users (8 non-diabetic, 10 Type 1 diabetic) were studied in high salt balance, a state of maximal RAA System suppression. Progestational and androgenic activity of the progestin in each OC was standardized to that of the reference progestin norethindrone. Renal plasma flow (RPF) was measured by paraaminohippurate clearance at baseline and in response to angiotensin converting enzyme (ACE)-inhibition. There was a positive correlation between OC progestational activity and the RPF response to ACE-inhibition (r=0.52, p=0.03). Similar results were noted with OC androgenic activity (r=0.54, p=0.02). On subgroup analysis, only non-diabetic subjects showed an association between progestational activity and angiotensin-dependent control of the renal circulation (r=0.71, p=0.05 non-diabetic; r=0.14, p=0.7 diabetic; p=0.07 between groups). Similar results were noted with respect to androgenic activity (r=0.88, p=0.005 non-diabetic; r=−0.33, p=0.3 diabetic; p=0.002 between groups). Our results suggest that the OC progestin component is a significant influence on the degree of angiotensin-dependent control of the renal circulation, though these findings may not apply to women with diabetes

The surprising external upturn of the Blue Straggler radial distribution in M55

By combining high-resolution HST and wide-field ground based observations, in ultraviolet and optical bands, we study the Blue Straggler Star (BSS) population of the low density galactic globular cluster M55 (NGC 6809) over its entire radial extent. The BSS projected radial distribution is found to be bimodal, with a central peak, a broad minimum at intermediate radii, and an upturn at large radii. Similar bimodal distributions have been found in other globular clusters (M3, 47 Tucanae, NGC 6752, M5), but the external upturn in M55 is the largest found to date. This might indicate a large fraction of primordial binaries in the outer regions of M55, which seems somehow in contrast with the relatively low (\sim 10%) binary fraction recently measured in the core of this cluster.Comment: in press on Ap

The Temperature and Cooling Age of the White-Dwarf Companion to the Millisecond Pulsar PSR B1855+09

We report on Keck and {\em Hubble Space Telescope} observations of the binary millisecond pulsar PSR B1855+09. We detect its white-dwarf companion and measure \mv=25.90\pm0.12 and \mi=24.19\pm0.11 (Vega system). From the reddening-corrected color, (\mv-\mi)_0=1.06\pm0.21, we infer a temperature \Teff=4800\pm800 K. The white-dwarf mass is known accurately from measurements of the Shapiro delay of the pulsar signal, \Mcomp=0.258^{+0.028}_{-0.016} \Msun. Hence, given a cooling model, one can use the measured temperature to determine the cooling age. The main uncertainty in the cooling models for such low-mass white dwarfs is the amount of residual nuclear burning, which is set by the thickness of the hydrogen layer surrounding the helium core. From the properties of similar systems, it has been inferred that helium white dwarfs form with thick hydrogen layers, with mass \simgt3\times10^{-3} \Msun, which leads to significant additional heating. This is consistent with expectations from simple evolutionary models of the preceding binary evolution. For PSR B1855+09, though, such models lead to a cooling age of $\sim10$Gyr, which is twice the spin-down age of the pulsar. It could be that the spin-down age were incorrect, which would call the standard vacuum dipole braking model into question. For two other pulsar companions, however, ages well over 10 Gyr are inferred, indicating that the problem may lie with the cooling models. There is no age discrepancy for models in which the white dwarfs are formed with thinner hydrogen layers (\simlt3\times10^{-4} \Msun).Comment: 7 pages, 1 figure, aas4pp2.sty. Accepted for publication in ApJ

Photoactivation of lysosomally sequestered sunitinib after angiostatic treatment causes vascular occlusion and enhances tumor growth inhibition

The angiogenesis inhibitor sunitinib is a tyrosine kinase inhibitor that acts mainly on the VEGF and PDGF pathways. We have previously shown that sunitinib is sequestered in the lysosomes of exposed tumor and endothelial cells. This phenomenon is part of the drug-induced resistance observed in the clinic. Here, we demonstrate that when exposed to light, sequestered sunitinib causes immediate destruction of the lysosomes, resulting in the release of sunitinib and cell death. We hypothesized that this photoactivation of sunitinib could be used as a vaso-occlusive vascular-targeting approach to treating cancer. Spectral properties of sunitinib and its lysosomal accumulation were measured in vitro. The human A2780 ovarian carcinoma transplanted onto the chicken chorioallantoic membrane (CAM) and the Colo-26 colorectal carcinoma model in Balb/c mice were used to test the effects of administrating sunitinib and subsequently exposing tumor tissue to light. Tumors were subsequently resected and subject to immunohistochemical analysis. In A2780 ovarian carcinoma tumors, treatment with sunitinib+light resulted in immediate specific angio-occlusion, leading to a necrotic tumor mass 24 h after treatment. Tumor growth was inhibited by 70% as compared with the control group (**P= 4; P = 0.0002). Histology revealed that photoactivation of sunitinib resulted in a change in tumor vessel architecture. The current results suggest that the spectral properties of sunitinib can be exploited for application against certain cancer indications

The ``Outside-In'' Outburst of HT Cassiopeiae

We present results from photometric observations of the dwarf nova system HT Cas during the eruption of November 1995. The data include the first two--colour observations of an eclipse on the rise to outburst. They show that during the rise to outburst the disc deviates significantly from steady state models, but the inclusion of an inner-disc truncation radius of about 4 $R_{wd}$ and a ``flared'' disc of semi-opening angle of $10^{\circ}$ produces acceptable fits. The disc is found to have expanded at the start of the outburst to about $0.41R_{L1}$, as compared to quiescent measurements. The accretion disc then gradually decreases in radius reaching $<0.32R_{L1}$ during the last stages of the eruption. Quiescent eclipses were also observed prior to and after the eruption and a revised ephemeris is calculated.Comment: 9 pages, 11 figures, to appear in MNRA