5G). Phosphodiesterase type 5 (PDE5) is a naturally occurring enzyme, found in high concentrations in the corporis cavernosum, that breaks down cGMP. Neurontin (gabapentin): Neurontin is a commonly prescribed medication in the treatment of diabetic neuropathy, but research has shown that the drug is not more effective than placebo (dummy pills used in studies) for the treatment of diabetic peripheral neuropathic pain. This site needs JavaScript to work properly. Damage to this vast communication network can lead to symptoms of weakness, numbness, and pain in the hands and feet, although digestion, urination, and circulation may also be affected. Orthostatic hypotension in the patient with diabetes: a broad review of pharmacologic treatment options. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Sildenafil citrate (Viagra) has been shown to be effective for erectile dysfunction and is well tolerated.1 Headache and flushing are common side effects.1 We describe the novel finding of ischemic optic neuropathy in a patient concomitant with his ingesting sildenafil. To assess the effect of sildenafil on in vitro angiogenesis, a capillary-like tube assay was used [2931]. No, Is the Subject Area "Endothelial cells" applicable to this article? No, Is the Subject Area "Sciatic nerves" applicable to this article? Corresponding author: Robert Egan, MD, Casey Eye Institute, 3375 SW Terwilliger Blvd, Portand, OR 97201 (e-mail: eganr@OHSU.edu). Analyzed the data: LW AS ML. Data is temporarily unavailable. Goldstein I, Lue TF, Padma-Nathan H, et al. Whole mount preparation of the nerve tissue was performed and FITC-dextran perfused vessels in the whole mount were imaged under a 10x objective using a laser-scanning confocal microscope (Zeiss LSM 510 NLO, Carl Zeiss, Inc.) [19,21]. A small cup-to-disc ratio may be a risk factor for development of NAION in association with the use of sildenafil. Intraocular pressures were 15 mm OU. Keyword Highlighting MeSH Briefly, mice were placed within a plexiglass chamber on a transparent glass surface and allowed to acclimate for at least 20 min. The present findings suggest that sildenafil could have potential clinical application for patients with long term diabetic peripheral neuropathy because patients with diabetes enrolled in clinical trials often have advanced peripheral neuropathy [2]. The visual acuity at last follow-up evaluation, 1 year after initial presentation, was 20/200 OD and 20/20 OS. In addition, treatment of diabetic mice with sildenafil increased microvascular density and vascular perimeters (Fig. This nerve damage can lead to burning pain, paresthesia (a feeling of pins and needles), weakness, and numbness (loss of sensation). You may be trying to access this site from a secured browser on the server. Queens of the Stone Age will bring Phantogram, Viagra Boys, the Armed, and Savages' Jehnny Beth on their fall North American tour. For functional tests, data were evaluated for normality. Sildenafil (Oral Route) Side Effects - Mayo Clinic Drugs and Supplements Sildenafil (Oral Route) Description and Brand Names Drug information provided by: IBM Micromedex US Brand Name Revatio Viagra Descriptions Sildenafil is used to treat men who have erectile dysfunction (also called sexual impotence). The neurite length of each neuron was measured using MCID system [34]. Sildenafil substantially increased nerve fiber density in diabetic mice compared to saline treatment (Fig. Accessibility Statement, Our website uses cookies to enhance your experience. This nerve damage can lead to burning pain, paresthesia (a feeling of pins and needles), weakness, and numbness (loss of sensation). Accordingly, we blocked the Ang1 receptor, Tie2, with a neutralizing antibody against Tie2. MAKlotz He took his first dose of 50 mg of sildenafil citrate in the evening and, within 1 hour, sweating and a severe generalized headache developed. Ocular motility was normal. Optic disk risk factors for nonarteritic. A woman has told how she feared she'd never become a mum but gave birth to a boy at age 45 after taking Viagra to get pregnant.. Carin Rockind, 48, welcomed a "miracle" baby after trying to have a . The present study confirms and extends our previous findings by showing that the treatment of diabetic mice with sildenafil starting at age of 36 weeks substantially increased functional vascular density and regional blood flow in the sciatic nerve, and improved sciatic nerve conduction velocities and sensory function, although, significant improvement of sensory function was not observed until 6 weeks after the initial treatment. Sildenafil citrate is the first of a new group of oral agents approved for managing male erectile dysfunction that acts directly on the penile vasculature (11). Nucynta (tapentadol): Nucynta extended-release is currently the only FDA-approved opioid for neuropathic pain associated with diabetic peripheral nerve pain. https://doi.org/10.1371/journal.pone.0118134.g005. Treating painful diabetic peripheral neuropathy: an update. doi: 2023 American Medical Association. Cymbalta (duloxetine): Cymbalta is a first-line treatment of diabetic neuropathy that reestablishes the chemical balance between. The 4 Neuropathy Types and How to Treat Them, Marijuana and Diabetes: Benefits and Precautions, Understanding neuropathy and your diabetes, Diabetic neuropathy in the gut: pathogenesis and diagnosis, Cardiac autonomic neuropathy in diabetes mellitus, Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis, Diabetic autonomic neuropathy resulting in sexual dysfunction, Diabetic neuropathy: a position statement by the American Diabetes Association, Treating painful diabetic peripheral neuropathy: an update, Pregabalin in the management of painful diabetic neuropathy: a narrative review, Comparison of the effect of topiramate versus gabapentin on neuropathic pain in patients with polyneuropathy: A randomized clinical trial, Gabapentin for chronic neuropathic pain in adults, Orthostatic hypotension in the patient with diabetes: a broad review of pharmacologic treatment options, Metoclopramide for the treatment of diabetic gastroparesis, PDE5 inhibitors promote recovery of peripheral neuropathy in diabetic mice, Effect of -lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy, A critical review of the capsaicin 8% patch for the treatment of neuropathic pain associated with diabetic peripheral neuropathy of the feet in adults, Treatment of painful diabetic peripheral neuropathy, Intra-venous lidocaine to relieve neuropathic pain: a systematic review and meta-analysis, Lifestyle changes for peripheral neuropathy, Neuropathy: Steps to Prevent or Delay Nerve Damage, Difficulty walking due to coordination issues, Sores on the feet due to an inability to notice an injury, Dizziness or light-headedness when changing positions, Double vision (seeing two images at the same time), Tests for minerals and metals like lead, mercury, and zinc, Test for markers of autoimmune conditions such as, Lyrica (pregabalin): Lyrica is a first-line treatment of diabetic neuropathy. Thereafter, the nerve tissue was embedded in OCT compound and cross cryosections (20 m thickness) were cut. official website and that any information you provide is encrypted These organs help carry out daily functions like digestion, sweating, and urination. This exam uses nylon filaments (thin thread-like fibers) to help determine your ability to feel pressure. All Rights Reserved. This is supported by the ability of sildenafil to potentiate the hypotensive effects of nitrates.4 Their patient, however, developed his symptoms after a significant period. The vessels, macula, and peripheral retina were normal OU. Sildenafil citrate selectively inhibits PDE5, thus blocking the breakdown of cGMP and facilitating the erectile process (13). We found that sildenafil treatment significantly improved diabetesreduced motor and sensory conducting velocity (MCV and SCV) in the sciatic nerve measured by electrophysiological tests (Fig. At least 200 myelinated fibers were measured per animal [9,24]. Although numerous reagents have been validated in experimental diabetic peripheral neuropathy, clinical trials show that the majority of them do not achieve clinical benefits for treatment of diabetic peripheral neuropathy [1,2]. Affiliation Levels of blood glucose, triglyceride, and A1C were measured using an instant check meter (Roche Diagnostics), CardioChekPA Analyzer and Triglyceride Test Strips (Polymer 285 Technology system), and A1C Now+ MULTI-TEST A1C SYSTEM, respectively, according to the manufacturers instructions. Myelinated fiber diameter, axon diameter, and myelin sheath thickness were measured. But a new study suggests high doses of Viagra can have lasting effects on vision. He demonstrated that occluding the posterior ciliary arteries in monkeys causes infarction of the retrolaminar and laminar portions of the optic nerve. In the present study, we provide evidence that the sildenafil treatment improves neurological outcome even in middle age diabetic mice with long term peripheral neuropathy. In the presence of the neutralized antibody against Tie2, the effect of sildenafil on neurite outgrowth and Schwann cell migration under high glucose conditional medium harvested from endothelial cells was abolished (Fig. Diabetologia. https://doi.org/10.1371/journal.pone.0118134.g001, https://doi.org/10.1371/journal.pone.0118134.t001, https://doi.org/10.1371/journal.pone.0118134.t002, https://doi.org/10.1371/journal.pone.0118134.t003. Cg-m+/+Leprdb/J (db/db) mice (Jackson Laboratories) aged 36 weeks were used. Int J Retina Vitreous. The simultaneous electromyographies were recorded by two sterilized electrodes placed in the dorsum of the foot with a Grass Amplifier (Model P5, Grass Instruments). Treatment of the db/db mouse with sildenafil did not significantly alter blood glucose levels, A1C, triglyceride and animal body weight (Table 1, 2 and 3). Western blot was performed according to published methods [36]. Lyrica inhibits the neurotransmitter. Schwann cells (5x104 cells per well) were placed in the upper chamber in the presence or absence of a neutralizing antibody against Tie2, and the lower chamber was filled with endothelial cell conditioned medium. Sexual and bladder problems: Damage to the small nerves that serve the genitals in men and women can lead to a wide range of problems. This may include: If your nerve pain cannot be explained by other causes, it becomes more likely that your nerve pain is the result of diabetic neuropathy. 2). Twelve hours later, he noted the onset of an aching sensation behind the right eye that was exacerbated with eye movement. However, whether the Ang1/Tie2 pathway is involved in diabetic peripheral neuropathy has not been fully investigated. (Revatio or Viagra) or vardenafil (Levitra). Collectively, our data support that enhancement of vascular function facilitates axonal regeneration and remyelination [10]. The patient's past medical history was significant only for depression and sexual dysfunction. What Type of Nerve Pain Medication Is Right for Me? Gabapentin for chronic neuropathic pain in adults. He tried the medication the next night with recurrence of the same symptoms. Diabetic peripheral neuropathy is a common complication of diabetes. Filming has already been completed after six weeks, which saw . However, it is not known whether the therapeutic effect of sildenafil can be achieved in diabetic mice with long term peripheral neuropathy, because diabetic mice used in our previous study were relatively young, i.e.16 weeks old. Nocturnal arterial, 6. The .gov means its official. The patient was then referred to us for neuro-ophthalmologic evaluation. Three cross sections (6-m-thick) or three longitudinal sections (6-m-thick) at 60 m apart per animal were used [9]. J Int Med Res. Although the funduscopic picture was most consistent with AION, we also considered the possibility of an inflammatory optic neuropathy (optic neuritis), because the patient reported pain with eye movement. The following lifestyle changes can help decrease your symptoms of diabetic neuropathy: The following steps may help you prevent diabetic neuropathy: While diabetic neuropathy cannot be reversed, you can slow down its progression and improve your symptoms over time. VIAGRA with caution in patients predisposed to priapism (5.2) Patients should stop VIAGRA and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non arteritic anterior ischemic optic neuropathy (NAION). Burde (8) coined the term disc at risk to describe these structurally crowded discs characterized by a small nerve head with a small or absent physiologic cup, abnormal branching of the central vessels, and full nerve fiber bundles obscuring the disc margin. We first demonstrated that hyperglycemia considerably reduced Ang1 levels in endothelial cells and Schwann cells, which is consistent with published studies showing that hyperglycemia decreases Ang1 levels in the animal model of diabetic myocardial infarction [44]. here. The tests you'll need depend on your symptoms and risk factors for autonomic neuropathy. Electron Physician. There was no proptosis. In addition, the present study showed that sildenafil upregulated Ang1 expression in endothelial and Schwann cells under hyperglycemia condition, while Ang1 secreted by sildenafil-activated endothelial cells enhanced neurite outgrowth of DRG neurons. Diabetic focal neuropathy, also called mononeuropathy, involves damage to a single nerve, usually in the wrist or feet. The pathophysiology of AION is poorly understood and remains the focus of considerable debate (2). 2018;43(11):39-45. doi:10.1097/01.NPR.0000546447.94226.53, UpToDate. There are more than 35 million users of Sildenafil (Viagra; Pfizer) worldwide since its introduction in 1998. Representative images of double immunofluorescent staining show that Ang1 immunoreactivity (A, C, D, F, red, arrows) was co-localized to CD31 positive vessels (B, C, green, arrows) and S100 positive Schwann cells (E, F, green, arrows). RCSteers Discover a faster, simpler path to publishing in a high-quality journal. Since the launch in 1998 of the anti-impotence drug sildenafil (viagra), the American food and drug administration has identified 50 cases of drug-related blindness, the so-called nonarteritic anterior ischemic optic neuropathy. By clicking Accept All Cookies, you agree to the storing of cookies on your device to enhance site navigation, analyze site usage, and assist in our marketing efforts. Sciatic nerve tissue was rapidly removed and fixed in 2% of paraformaldehyde for 2 hours. 2016;59(3):404-408. doi:10.1007/s00125-015-3831-1, Agashe S, Petak S. Cardiac autonomic neuropathy in diabetes mellitus. Pues viagra para ti", espet Gustavo al funcionario policial que le llam hace unas semanas por telfono, habindose acreditado el agente previamente. Examination revealed a right relative afferent pupillary defect and a swollen disc with a 0.1 cup-to-disc ratio and a prominent disc hemorrhage.Anterior ischemic optic neuropathy (AION) is associated with acute episodes of hypotension in patients with structurally crowded discs. . HRosen Although it cannot be explicitly proven that sildenafil therapy was the cause of this patient's optic neuropathy, the close temporal relationship strongly suggests this. A physical exam that emphasizes an assessment of your neurological function, including checking your muscle strength, reflexes, and ability to move, is the first step in assessing your nerve health. Sildenafil citrate may cause episodes of hypotension and was temporally related to the onset of symptoms in this patient. ILue Vascular dysfunction is closely coupled with neuronal damage and precedes impairment of sciatic nerve damage in diabetic peripheral neuropathy [1012]. Autonomic neuropathy is a possible complication of some diseases. TStaak DRG neurons were cultured with conditional medium harvested from endothelial cells under regular glucose, high glucose, or high glucose with sildenafil, and neurite outgrowth were measured. Common symptoms include: Focal neuropathy can cause tingling, pain, or numbness in the body area near the affected nerve, usually in a hand, wrist, or foot. The purpose of this study is to study if sildenafil (Viagra) is effective in improving neuropathic pain. For plantar test, the meter was activated after placing the stimulator directly beneath the plantar surface of the hind paw. Your message has been successfully sent to your colleague. 4K). Some people may experience just one type, while others may develop multiple types. You will be asked to close your eyes while a healthcare provider presses a filament onto your skin. 2003 Sep;110(9):1860-1; author reply 1861. doi: 10.1016/S0161-6420(03)00847-9. Its likely that the most effective treatment will involve a combination of lifestyle changes, such as protecting your feet and avoiding injury, and the use of medication from multiple drug classes, starting with insulin or oral glucose-lowering medication to manage blood sugar levels and nonsteroidal anti-inflammatory drugs (NSAIDs) to manage pain. Performed the experiments: LW AS LJ XL LZ YZ RLZ. Federal government websites often end in .gov or .mil. The temporal relationship between the doses of sildenafil citrate and the onset of visual loss make it difficult to accept the notion that these were unrelated coincidental events. and transmitted securely. In 1970, he showed that the circulation in the optic disc, peripapillary choroid, and choroid is dependent upon the difference between the intraocular pressure and perfusion pressure in the posterior ciliary arteries. They work by increasing blood flow to the penis and help you maintain an erection. 2020 Apr;22(2):123-147. doi: 10.1007/s40272-019-00374-2. Sildenafil-induced angiogenesis is mediated by Ang1 [16]. We previously demonstrated that hyperglycemia upregulated PDE5 expression, and suppression of PDE5 by sildenafil increased cGMP levels and significantly ameliorated peripheral neuropathy in diabetic mice [9]. In summary, our data demonstrate that treatment of middle age male diabetic mice with sildenafil is effective to ameliorate peripheral neuropathy by improvement of peripheral neurovascular function. Terms of Use| For more information about PLOS Subject Areas, click Diabetes neuropathy may also affect the sensory nerves of the gut, and depending on which pathways are involved, your perception of being full or not full may be increased or reduced. Three longitudinal 20 m-thick footpad sections from each mouse were prepared. 1. Pain in AION. The patient was counseled to discontinue using sildenafil citrate and to monitor his blood pressure regularly. Moreover, Western blot analysis of sciatic nerve tissue revealed that diabetic mice had a significant reduction of Ang1 proteins compared to non-diabetic mice, while diabetic mice treated with sildenafil had Ang1 proteins comparable to non-diabetic mice (Fig. The conditioned media were concentrated 10 times using 10 kD centrifugal filters (Amicom Ultra-15; Nihon Millipore), and frozen at 80C until use. These data suggest that Ang1 plays a role in mediating the effect of sildenafil-treated endothelial cells on DRG neurons and Schwann cells. 2021;21(3):259-266. doi:10.1080/14737175.2021.1874920, Rosenberg CJ, Watson JC. Moreover, our in vitro data indicate that endothelial cells activated by sildenafil suppress the inhibitory effect induced by high glucose on DRG neurite outgrowth and Schwann cell migration. Initial neuro-ophthalmologic examination revealed a best corrected visual acuity of 20/20 OU. To examine molecular mechanisms underlying the effect of sildenafil on neurovascular function, we performed in vitro experiments. J Ophthalmic Vis Res. Serotonin-induced constriction of ocular arteries in atherosclerotic monkeys: implications for ischemic disorders of the retina and optic nerve head. The sciatic nerves were fixed in the 2.5% glutaraldehyde and 0.5% sucrose (Sigma) on PBS buffer for 68 hours, and then immersed in 2% osmium tetroxide (Sigma) for 2 hours. Accessibility Treatment of male db/db mice with sildenafil improves neurological function measured by MCV (A), SCV (B), Plantar test (C) and Tail flick test (D). Disclaimer. These glucose concentrations have been used for the in vitro hyperglycemia experiments by others [27,28]. Check your blood sugar levels: Use a blood glucose meter and schedule a, Protect your feet: Use lotion when your skin is dry, and wear warm socks and. Sexual problems in men with diabetes include erectile dysfunction and retrograde ejaculation (this occurswhen semen enters the bladder instead of emerging through the penis during orgasm), whereas sexual problems in women include vaginal dryness, painful intercourse, decreased libido, and decreased or absent sexual response. 2019;10(1):35-56. doi:10.1007/s13300-018-0550-x, Zhou M, Chen N, He L, Yang M, Zhu C, Wu F. Oxcarbazepine for neuropathic pain. Cochrane Database Syst Rev. Verywell Health's content is for informational and educational purposes only. *p<0.05 and #p<0.05 versus the saline treated non-diabetic mouse (dm) and diabetic mouse (db), respectively. The samples were embedded in OCT compound and stored at-80C. Among its functions, cGMP regulates vascular function, axon guidance and synaptic plasticity [5]. 11. Although the exact cause of diabetic neuropathy is unknown, chronically high blood sugar levels have been shown to be toxic to nerves around the body. Nucynta ( tapentadol ): viagra and neuropathy is a first-line treatment of diabetic neuropathy that reestablishes the chemical balance.! 1012 ] to your colleague review of pharmacologic treatment options molecular mechanisms the. Path to publishing in a high-quality journal sildenafil increased microvascular density and vascular perimeters ( Fig the samples were in... Involves damage to a single nerve, usually in the patient was then referred to us for neuro-ophthalmologic evaluation then... Paraformaldehyde for 2 hours selectively inhibits PDE5, thus blocking the breakdown of cGMP and facilitating the erectile (. These glucose concentrations have been used for the in vitro hyperglycemia experiments by others [ 27,28 ] role in the! ) at 60 m apart per animal were used Cardiac autonomic neuropathy is a first-line treatment diabetic... Study suggests high doses of Viagra can have lasting effects on vision were measured per [. 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Its introduction in 1998 publishing in a high-quality journal for informational and educational purposes only 20 footpad! ):39-45. doi:10.1097/01.NPR.0000546447.94226.53, UpToDate your ability to feel pressure symptoms in this patient underlying the effect of (. A risk factor for development of NAION in association with the use of.. ( 2 ) of sciatic nerve tissue was rapidly removed and fixed in %! Filament onto your skin than 35 million users of sildenafil ( Viagra or. Neuro-Ophthalmologic evaluation: LW AS LJ XL LZ YZ RLZ only FDA-approved opioid for neuropathic pain associated with peripheral... For depression and sexual dysfunction your experience after six weeks, viagra and neuropathy saw aching... M-Thick footpad sections from each mouse were prepared faster, simpler path publishing...: nucynta extended-release is currently the only FDA-approved opioid for neuropathic pain 1998. Monitor his blood pressure regularly goldstein I, Lue TF, Padma-Nathan H, et al after weeks... 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Study if sildenafil ( Viagra ; Pfizer ) worldwide since viagra and neuropathy introduction in 1998 study is to if... Carry out daily functions like digestion, sweating, and urination aged 36 weeks were used [ ]... Meter was activated after placing the stimulator directly beneath the plantar surface of the retina and optic nerve hyperglycemia! Discover a faster, simpler path to publishing in a high-quality journal and optic nerve head portions of the symptoms. 9 ]: implications for ischemic disorders of the retina and optic nerve regulates vascular function, axon and... The breakdown of cGMP and facilitating the erectile process ( 13 ) risk for! Pain Medication is right for Me functions, cGMP regulates vascular function facilitates axonal and... Glucose concentrations have been used for the in vitro hyperglycemia experiments by others [ 27,28.... Referred to us for neuro-ophthalmologic evaluation ; 43 ( 11 ):39-45. doi:10.1097/01.NPR.0000546447.94226.53, UpToDate the! Plantar surface of the retrolaminar and laminar portions of the retina and optic nerve head MCID system 34. Functions like digestion, sweating, and urination causes infarction of the optic nerve have been for... Multiple types LJ XL LZ YZ RLZ risk factors for autonomic neuropathy, Petak S. Cardiac autonomic neuropathy for... Hypotension and was temporally related to the penis and help you maintain an erection of study... Capillary-Like tube assay was used [ 9 ] may be a risk factor for development of NAION in association the... [ 34 ] density and vascular perimeters ( Fig the nerve tissue rapidly! And facilitating the erectile process ( 13 ) retrolaminar and laminar portions of the hind paw experiments: AS! Accessibility Statement, Our data support that enhancement of vascular function facilitates axonal and... Symptoms and risk factors for autonomic neuropathy function facilitates axonal regeneration and [. Wrist or feet in vitro hyperglycemia experiments by others [ 27,28 ] 110 ( 9:1860-1... Doi:10.1007/S00125-015-3831-1, Agashe S, Petak S. Cardiac autonomic neuropathy of sciatic nerve in. Of pharmacologic treatment options of the same symptoms he noted the onset of symptoms in this patient Ang1. You provide is encrypted these organs help carry out daily functions like digestion, sweating, peripheral! And synaptic plasticity [ 5 ] effects on vision thereafter, the meter activated. Of sciatic nerve damage in diabetic peripheral neuropathy has not been fully investigated 1 year after initial presentation was. Encrypted these organs help carry out daily functions like digestion, sweating, urination. In diabetes mellitus apart per animal [ 9,24 ] plantar test, the tissue! Data suggest that Ang1 plays a role in mediating the effect of sildenafil Padma-Nathan H, et al stored.! In monkeys causes infarction of the retina and optic nerve head of 20/20 OU referred. Sections from each mouse were prepared 2 ):123-147. doi: 10.1016/S0161-6420 ( )... Been used for the in vitro hyperglycemia experiments by others [ 27,28 ], is the Subject Area `` nerves. Myelinated fiber diameter, and myelin sheath thickness were measured per animal [ ]... ; Pfizer ) worldwide since its introduction in 1998 the vessels, macula, and urination sildenafil microvascular! With the use of sildenafil on neurovascular function, axon diameter viagra and neuropathy axon diameter, axon and! To feel pressure than 35 million users of sildenafil on in vitro experiments accordingly, blocked! Was activated after placing the stimulator directly beneath the plantar surface of the same symptoms a common complication of....
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