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Pharmacogenomics and Personalized... 2021Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5...
BACKGROUND
Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5 (CYP3A4/5) in the liver. Peripheral edema emerges as the major adverse drug reaction to amlodipine and is the primary reason for discontinuation of amlodipine therapy. However, genetic changes in may lead to changes in the tolerability of amlodipine.
PURPOSE
In this study, we were interested whether variants in CYP3A5 have a role to play in amlodipine-induced peripheral edema.
METHODS
A total number of 240 Chinese Han patients that have experienced hypertension were included in the study. Sixty-four patients had experienced amlodipine-induced peripheral edema, while the remaining 176 patients with no history of edema formed the control group. Twenty-four single-nucleotide polymorphisms (SNPs) of gene were sequenced by targeted region sequencing method. The relationship of these genetic variants with amlodipine-induced peripheral edema risk was assessed using logistic regression.
RESULTS
The allele frequencies of (rs15524), (rs4646453) and (rs776746) were significantly different between cases and controls (<0.05). The (CC) or (AA) carriers showed an increased risk of amlodipine-induced peripheral edema in dominant model. Meanwhile, patients carrying (AC/AA) showed a reduced risk of peripheral edema. Furthermore, we found a strong linkage disequilibrium among rs15524, rs4646453 and rs776746.
CONCLUSION
Our study reveals for the first time that and were associated with amlodipine-induced peripheral edema in Chinese Han patients with hypertension. However, further studies comprising larger number of samples, more related genes and other factors are wanted.
PubMed: 33564260
DOI: 10.2147/PGPM.S291277 -
American Journal of Ophthalmology Case... Mar 2022This case report describes the therapeutic management of a 61-year-old male who experienced aquarium coral keratoconjunctivitis caused by exposure to palytoxin and...
PURPOSE
This case report describes the therapeutic management of a 61-year-old male who experienced aquarium coral keratoconjunctivitis caused by exposure to palytoxin and provides an additional resource to raise awareness and treat patients with ocular exposure to palytoxin.
OBSERVATIONS
A 61-year-old male inadvertently touched his left eye while cleaning an aquarium. Within 24 hours, pain, redness and visual blurring was noted. After 48 hours his best corrected visual acuity was measured at 20/25 on the right eye and 20/200 on the left. A thick mucopurulent discharge was present with associated conjunctival edema. The corneal epithelium was denuded centrally and inferiorly with subepithelial infiltrates peripherally. The patient was treated with topical moxifloxacin (0.5%) drops 6x/day and prednisolone acetate (1%) 4x/day. He was seen for follow up 48 hours later with a significant improvement in discomfort. Vision had improved to 20/60 with resolution of conjunctival edema, partial corneal epithelialization and reduced erythema. Cultures for culture and sensitivity returned as normal. The patient's steroid regime was gradually tapered during reassessments at four and ten days by which time the left eye acuity had returned to 20/25 with no symptoms. Therapy was discontinued with the exception of artificial tears. The patient continued to do well at his 42-day follow-up appointment with persistent corneal epithelialization, absence of infiltrates and a stable visual acuity of 20/25 in the affected eye. His local optometrist confirmed that the acuity was consistent with measurements obtained prior to the insult.
CONCLUSIONS
The combination of moxifloxacin eye drops and prednisolone acetate eye drops were effective in treating the patient's aquarium coral keratoconjunctivitis as after being treated the patient regained his baseline visual acuity in the affected eye (best corrected visual acuity of 20/25).
IMPORTANCE
Currently, there are only a handful of case-reports published on ocular exposure to palytoxin. This case report will add to the literature by providing an additional resource for health care providers, in the treatment of patients with ocular exposure to palytoxin and increasing awareness to this rare condition.
PubMed: 35128163
DOI: 10.1016/j.ajoc.2022.101326 -
Kidney International Reports Jan 2024Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and...
INTRODUCTION
Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema.
METHODS
A total of 4 clinical visits were performed before, during, and after a 6-day bicycle ride in 13 ultracyclists (5 female, 8 male) including serial laboratory analyses of blood and urine, bioelectrical impedance, and echocardiography. Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema.
RESULTS
Participants covered a mean distance of 1205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable ( = 0.479); however, body composition changed with increasing total body water (TBW) (+1.98 l ± 1.37, = 0.003) and plasma volume (+18.86 % ± 10.7, < 0.001). A significant increase in N-terminal pro brain natriuretic peptide (NT-proBNP) (+297.99 ng/l ± 190.42, < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both ≤ 0.033). On recovery, changes partly resolved. Although urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/l ± 23.88, = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, = 0.004) and copeptin (+38.28 pg/ml ± 18.90, < 0.001) increased steadily until day 6.
CONCLUSION
Ultracycling over multiple days induces extracellular volume expansion, peripheral edema, and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition.
PubMed: 38312776
DOI: 10.1016/j.ekir.2023.10.025 -
Translational Vision Science &... Jun 2020To assess the influence of limbal metabolic support on corneal edema during scleral-lens (SL) and soft-contact-lens (SCL) wear for healthy lens wearers.
PURPOSE
To assess the influence of limbal metabolic support on corneal edema during scleral-lens (SL) and soft-contact-lens (SCL) wear for healthy lens wearers.
METHODS
A two-dimensional (2D) model of the cornea and sclera was designed on Comsol Multiphysics 5.4 along with SL and SCL architectures to mimic lens-wear induced hypoxia. The cornea is suffused with oxygen and metabolites from the limbus and aqueous humor. Air oxygen is supplied from and carbon dioxide is expelled to the atmosphere. Lens-oxygen permeability () was adjusted to investigate lens-wear safety against edema in different wear conditions. The 2D concentrations of oxygen, carbon dioxide, bicarbonate, lactate, sodium, chloride, glucose, and pH are quantified. Central-to-peripheral swelling of the cornea is determined by the change in stromal hydration caused by changing metabolite concentrations at the endothelium during hypoxia.
RESULTS
The metabolic model assesses central-to-peripheral corneal swelling with different types of lenses, and oxygen s. Limbal metabolic support reduces edema from the periphery to approximately 1 mm away from the central cornea. Despite thicker lens designs, the peripheral cornea exhibits practically zero swelling due to limbal metabolic support.
CONCLUSIONS
The metabolic model accurately predicts central-to-peripheral corneal edema with various contact-lens designs, post-lens tear-film thicknesses, and lens oxygen values. Despite the thicker periphery of most contact-lens designs, lactate and bicarbonate support from the limbus significantly reduces peripheral and mid-peripheral corneal edema, whereas oxygen has a lesser effect.
TRANSLATIONAL RELEVANCE
By utilizing metabolic kinetics, we provide a 2D computational tool to predict oxygenation safety across the entire cornea with various types and designs of contact lenses.
Topics: Contact Lenses, Hydrophilic; Cornea; Corneal Edema; Edema; Humans; Sclera
PubMed: 32832249
DOI: 10.1167/tvst.9.7.44 -
Translational Pediatrics Jul 2022Neonatal hypoxic-ischemic encephalopathy (HIE), a kind of hypoxic-ischemic brain damage caused by perinatal asphyxia, is the most crucial cause of neonatal death and...
BACKGROUND
Neonatal hypoxic-ischemic encephalopathy (HIE), a kind of hypoxic-ischemic brain damage caused by perinatal asphyxia, is the most crucial cause of neonatal death and long-term neurological dysfunction in children. We aimed to investigate the protective effects of micro (mi)R-27a on HIE in neonatal rats.
METHODS
A rat model of neonatal HIE was constructed by modification of the Rice-Vannucci model. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the expressions of miR-27a, FOXO1 messenger RNA (mRNA), interleukin-1β (IL-1β) mRNA, and tumor necrosis factor-α (TNF-α) mRNA, and western blot was applied to test the expression of FOXO1. In order to overexpress miR-27a, an intracerebroventricular injection (i.c.v) of miR-27a mimic was administered. We adopted 2,3,5-triphenytetrazolium chloride (TTC) staining and brain water content measurement to test the effects of miR-27a on the infarcted volume and edema in brain after HIE. Flow cytometry (FCM) analysis was applied to test the effects of miR-27a on the infiltrated peripheral immune cells in the rat brains after HIE.
RESULTS
We successfully established a rat model of neonatal HIE. It was revealed that the expressions of miR-27a decreased gradually after HIE, however, the expressions of FOXO1 mRNA increased. After injection of the miR-27a mimic, the expression of miR-27a in the rat HIE model brains was significantly upregulated, however, the expression of FOXO1 was robustly downregulated. Both TTC staining and brain water content showed that the infarcted volume and brain edema was markedly increased after HIE. Interestingly, the overexpression of miR-27a reduced the infarcted volume and edema induced by HIE. Additionally, RT-qPCR and FCM analysis showed that HIE lead to increases of IL-1β, TNF-α, and infiltrated immune cells. Overexpression of miR-27a could reduce the expressions of IL-1β mRNA and TNF-α mRNA, and the cell numbers of infiltrated peripheral macrophages and neutrophils in the brain.
CONCLUSIONS
MiR-27a plays protective roles by reducing infarct volume and brain edema, and inhibiting inflammatory factors and infiltrated peripheral immune cells by targeting FOXO1 in neonatal HIE rats.
PubMed: 35958013
DOI: 10.21037/tp-22-259 -
Ophthalmology Apr 2023We aimed to characterize the ocular phenotype of patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome and their...
Ophthalmic Manifestations of ROSAH (Retinal Dystrophy, Optic Nerve Edema, Splenomegaly, Anhidrosis, and Headache) Syndrome, an Inherited NF κB-Mediated Autoinflammatory Disease with Retinal Dystrophy.
PURPOSE
We aimed to characterize the ocular phenotype of patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome and their response to therapy.
DESIGN
Single-center observational case study.
PARTICIPANTS
Eleven patients with a diagnosis of ROSAH syndrome and mutation in ALPK1 were included.
METHODS
Patients with molecularly confirmed ROSAH syndrome underwent ophthalmic evaluation, including visual acuity testing, slit-lamp and dilated examinations, color fundus and autofluorescence imaging, fluorescein angiography, OCT, and electrophysiologic testing.
MAIN OUTCOME MEASURES
Visual acuity, electrophysiology, fluorescein angiography, and OCT findings.
RESULTS
Eleven individuals (6 female and 5 male patients) from 7 families ranging in age from 7.3 to 60.2 years at the time of the initial evaluation were included in this study. Seven patients were followed up for a mean of 2.6 years (range, 0.33-5.0 years). Best-corrected visual acuity at baseline ranged from 20/16 to no light perception. Variable signs or sequelae of intraocular inflammation were observed in 9 patients, including keratic precipitates, band keratopathy, trace to 2+ anterior chamber cells, cystoid macular edema, and retinal vasculitis on fluorescein angiography. Ten patients were observed to show optic disc elevation and demonstrated peripapillary thickening on OCT. Seven patients showed retinal degeneration consistent with a cone-rod dystrophy, with atrophy tending to involve the posterior pole and extending peripherally. One patient with normal electroretinography findings and visual evoked potential was found to have decreased Arden ratio on electro-oculography.
CONCLUSIONS
Leveraging insights from the largest single-center ROSAH cohort described to date, this study identified 3 main factors as contributing to changes in visual function of patients with ROSAH syndrome: optic nerve involvement; intraocular inflammation, including cystoid macular edema; and retinal degeneration. More work is needed to determine how to arrest the progressive vision loss associated with ROSAH syndrome.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found after the references.
Topics: Male; Female; Humans; Macular Edema; NF-kappa B; Electroretinography; Splenomegaly; Hypohidrosis; Evoked Potentials, Visual; Retinal Dystrophies; Optic Nerve; Edema; Hereditary Autoinflammatory Diseases; Inflammation; Headache; Fluorescein Angiography; Tomography, Optical Coherence
PubMed: 36332842
DOI: 10.1016/j.ophtha.2022.10.026 -
International Journal of Clinical and... 2021The present study aimed to elucidate the relationship between histologic changes and inflammatory markers in chronic rhinosinusitis (CRS). Inflammatory markers of CRS,...
The present study aimed to elucidate the relationship between histologic changes and inflammatory markers in chronic rhinosinusitis (CRS). Inflammatory markers of CRS, including eosinophil and neutrophil counts, the eosinophil-to-lymphocyte ratio, and the neutrophil-to-lymphocyte ratio, were investigated in tissues and peripheral blood. Inflammatory markers were evaluated according to the histologic changes of stromal edema, stromal fibrosis, and basement membrane (BM) thickening. Among 92 patients with CRS who underwent pathologic examinations, stromal edema, stromal fibrosis, and BM thickening were identified in 84.8%, 25.0%, and 53.3% of patients, respectively. Stromal edema and BM thickening were observed more frequently in CRS with nasal polyps than in CRS without nasal polyps ( = 0.001 and = 0.001, respectively). Tissue inflammatory markers differed according to the presence of histologic changes in tissues. In peripheral blood, however, only the eosinophil count differed according to BM thickening. Patients with two or more histologic changes had higher tissue eosinophil-to-lymphocyte ratios ( = 0.008) and eosinophil counts ( = 0.002) compared with subjects with no or one histologic change. Conversely, the tissue neutrophil-to-lymphocyte ratio and neutrophil count were higher in patients with no or one histologic change than in patients with two or more changes. Collectively, tissue inflammatory markers may be correlated with histologic changes in CRS. However, serum inflammatory markers have a limited ability to predict histologic changes in patients with CRS.
PubMed: 33936373
DOI: No ID Found -
Journal of the American Heart... Oct 2016Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis. (Meta-Analysis)
Meta-Analysis Review
Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights From the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials.
BACKGROUND
Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis.
METHODS AND RESULTS
After systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated. Summary relative risks and 95% CIs were calculated using random- or fixed-effects models according to between-study heterogeneity. In total, 24 randomized trials including 4894 patients met the inclusion criteria. Meta-analysis showed that the incidence of abnormal liver function (7.91% versus 2.84%; risk ratio [RR] 2.38, 95% CI 1.36-4.18), peripheral edema (14.36% versus 9.68%; RR 1.44, 95% CI 1.20-1.74), and anemia (6.23% versus 2.44%; RR 2.69, 95% CI 1.78-4.07) was significantly higher in the ERA group compared with placebo. In comparisons of individual ERAs with placebo, bosentan (RR 3.78, 95% CI 2.42-5.91) but not macitentan (RR 1.17, 95% CI 0.42-3.31) significantly increased the risk of abnormal liver function, whereas ambrisentan (RR 0.06, 95% CI 0.01-0.45) significantly decreased that risk. Bosentan (RR 1.47, 95% CI 1.06-2.03) and ambrisentan (RR 2.02, 95% CI 1.40-2.91) but not macitentan (RR 1.08, 95% CI 0.81-1.46) significantly increased the risk of peripheral edema. Bosentan (RR 3.09, 95% CI 1.52-6.30) and macitentan (RR 2.63, 95% CI 1.54-4.47) but not ambrisentan (RR 1.30, 95% CI 0.20-8.48) significantly increased the risk of anemia. ERAs were not found to increase other reported adverse events compared with placebo.
CONCLUSIONS
The present meta-analysis showed that the main adverse effects of treatment with ERAs were hepatic transaminitis (bosentan), peripheral edema (bosentan and ambrisentan), and anemia (bosentan and macitentan).
Topics: Anemia; Chemical and Drug Induced Liver Injury; Double-Blind Method; Edema; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27912207
DOI: 10.1161/JAHA.116.003896 -
International Angiology : a Journal of... Dec 2018The aim of this review was to discuss the different techniques of leg edema measurement that have been used in clinical trials to help determine the most appropriate... (Review)
Review
The aim of this review was to discuss the different techniques of leg edema measurement that have been used in clinical trials to help determine the most appropriate method of assessment and quantification for use in future research. Venoactive drugs such as micronized purified flavonoid fraction (MPFF) are established agents for the treatment of venous leg edema, but results from randomized-controlled trials vary depending on the method of edema assessment. The medical literature was searched for published articles using the terms "venous lower limb edema" and "method of edema assessment." Clinical trials performed with MPFF used leg circumference and optometry for leg edema assessment. Indirect methods of lower limb volume assessment can be made by measurement of leg circumference with a tape or Leg-O-Meter. These are reliable and standardized instruments and simple and rapid to perform. Leg circumference measurements can also be used to indirectly estimate leg volume using the Frustum method. Direct methods such as water displacement volumetry are generally regarded as the gold standard for measurement of lower limb volume with low inter- and intra-individual variability. Nevertheless, to minimize variation in results measurement conditions must be standardized. The reproducibility of optometry can be considered good when positioning of the limb is appropriate. Other techniques also exist such as ultrasound imaging, bioelectrical impedance, tomodensitometry, Dual X-ray absorptiometry, computed tomography and magnetic resonance imaging. The different methods may be used to measure different compartments of the leg with or without the foot volume. For all techniques, strict standardization of measurement conditions is mandatory. Patient heterogeneity and method of edema assessment impact clinical trial results. In particular, there are a number of error sources with several methods of assessment that can lead to variability in trial results. Consequently, pilot studies are required to validate new methods of edema assessment using innovative technologies.
Topics: Anthropometry; Edema; Electric Impedance; Humans; Lower Extremity; Patient Positioning; Peripheral Vascular Diseases; Predictive Value of Tests; Prognosis; Reproducibility of Results; Veins
PubMed: 30256052
DOI: 10.23736/S0392-9590.18.04057-9 -
Frontiers in Pediatrics 2023The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the...
INTRODUCTION
The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the medication (osmolarity or vesicant), and the need for central pressure monitoring. The utilization of peripheral intravascular catheters (PIVCs) has shown a notable increase in the number of patients being treated. Extended dwell or midline catheters are another peripheral access option in addition to PIVCs. However, there are currently no established guidelines on their placement.
OBJECTIVES
The aim of this study is to estimate the duration of dwell time for PIVCs, analyze the specific parameters affecting it, and develop recommendations for switching to extended dwell and midline catheter placement as an alternative to peripheral access.
METHODS
The study enrolled patients aged 0-18 years admitted to the pediatric intensive care unit (PICU) for over 24 h and managed with peripheral access only over 2 years (2019-2021).
MEASUREMENTS AND MAIN RESULTS
A total of 484 patients met the specified criteria. Patients who had peripheral access exhibited a lower PRISM score and a shorter length of stay in the PICU, with mean values of 18 (SD: 8.5) and 9.5 (SD: 6.4) days, respectively, compared with patients who had central access with mean values of 8.9 (SD: 5.9) and 5.7 (SD: 3.6) days, respectively. The PIVC dwell time was found to be 50.1 h (SD: 65.3) and required an average of 1.6 insertion attempts. Patients with three or more insertions exhibited an increased odds ratio of 5.2 (95% CI: 3.1-8.5) for receiving an extended dwell or midline insertion. Increased dwell time was associated with female gender, 59.5 h (< 0.001), first attempt insertion, 53.5 h (< 0.001), use of 24 Ga bore, 56.3 h (= 0.04), left-sided insertions, 54.9 (= 0.07), less agitation, 54.8 h (= 0.02), and less edema, 61.6 (< 0.001). Decreased dwell time was associated with the use of vancomycin infusion at 24.2 h (< 0.001) and blood transfusions at 29.3 h (< 0.001).
CONCLUSIONS
Extended catheters last longer than PIVCs in PICU patients. Extended catheter placement requires consideration of the length of treatment, as well as the overall body edema, the level of the patient's restlessness, and the need for vancomycin infusion or blood transfusions, as these factors reduce PIVC dwell time and expose the patients to painful insertions. For such cases, an extended dwell catheter may be a better option, even if the projected treatment time is less than 6 days.
PubMed: 37876526
DOI: 10.3389/fped.2023.1259395