Rebound Swelling Research Articles

The importance of vascular epithelial growth factor (VEGF) and inducible nitric oxide synthase (INOS) in rhinitis medicamentosa pathogenesis: An experimental rat model study.

Our aim in this study is to reveal the expression of Vascular Endothelial Growth Factor (VEGF) and Inducible Nitric Oxide Synthase (iNOS) in the pathogenesis of rhinitis medicamentosa (RM), which occurs as a result of the overdose and long-term use of topical nasal decongestants. In this study, 24 Wistar albino rats were divided into two groups as experimental and control groups. In the experimental group, 50 µl of 0.05% oxymetazoline (iliadin® merck) was applied intranasally to each nostril three times a day for 2 months with the help of a micropipette. 50 µl saline was applied to the control group. At the end of the second month, the rats were examined. RM was detected in the experimental group. Then the nasal tissues of the rats were removed and fixed with 10% phosphate buffered neutral formaldehyde (pH=7.4). Nasal tissues were decalcified in Morse's solution (10% sodium citrate and 22.5% formic acid). Histopathological evaluations of the preparations were stained using Masson Trichrome (TCM) and Hematoxylin Eosin (H&E) techniques and immunohistochemical examinations of the preparations were stained with VEGF and iNOS antibodies and photographed using the Leica DM6000B microscope and the Leica Application Suite Program. In the RM group, we found a significant increase in VEGF and iNOS expression in the nasal mucosa compared to the control group (p<0.001). We also observed the main histopathological changes in the nasal mucosa under a light microscope, including squamous metaplasia in the epithelium of the tunica mucosa, submucosal perivascular edema and degeneration of the submucosal glands. According to these results, increased expression levels of VEGF and iNOS play an important role in rebound swelling in RM pathogenesis.

Feasibility and initial efficacy of a multimodal swelling intervention after total knee arthroplasty: A prospective pilot study with historical controls

BackgroundSwelling after total knee arthroplasty (TKA) is often profound and persistent, increasing risks of DVT, infection, and wound dehiscence, and impairing rehabilitation. We investigated the feasibility and initial efficacy of a multimodal swelling control intervention (MSI), comprised of an inelastic adjustable compression garment (CG), manual lymph drainage (MLD) massage, and home exercise program (HEP) after total knee arthroplasty (TKA) compared to a control group. MethodsSixteen individuals (mean age 64.7 ± 7.1y) performed MSI for three weeks after TKA, through day 21 (D21). Outcome measures included patient satisfaction, safety, patient adherence, and swelling measured by Single Frequency Bioimpedance Assessment (SF-BIA). All outcomes were measured preoperatively and at postoperative D4, D7, D14, D21 and, three weeks after discontinuing MSI, on D42. Efficacy of MSI was calculated with Hedge’s g effect size estimates using the SF-BIA ratios for MSI versus CONTROL (N = 56; mean age 64.3 ± 9.3y) at key post operative time points. ResultsPatient satisfaction was 93% with no adverse events. Adherence to CG, MLD, and HEP were 85%, 99%, and 97% respectively. Peak swelling reduction with MSI was at D21 (Hedges’ g = 1.60 at D21 (95% CI 0.99, 2.21)). Minimal change in swelling was observed three weeks after cessation of MSI on D42. ConclusionsThe self-administered MSI program is feasible and demonstrated strong initial efficacy to control swelling after TKA. Minimal rebound swelling was observed once MSI was withdrawn at D21. Future studies should examine the efficacy of inelastic adjustable compression in a randomized controlled trial.

Compressibility of soft Iraqi soil stabilized with traditional Iraqi stabilizers (cement and lime)

This study shows an improvement of two types of clay soil brought from different parts of Iraq. The first soil (A) from Al - Zaafaraniya site in Baghdad governorate. The second soil (B) from Garma Ali site in the Al Basra governorate, Iraq. Soft clayey soils were treated by a combination of sulphate resistance Portland cement (PC) and Quicklime (LQ) to modify and stability. PC was added in percentages of 2,4,6,8 and 10%, as well as, LQ was added to 2 and 4%, of dry weight. Laboratory tests to determine specific gravity, Atterbergs limits and standard proctor test were conducted. Also, the main objective of this research is the concentrating on compression ratio (CR), the Rebound (Swelling) ratio (RR) and the stiffness during the modulus of elasticity (Es) for treated and natural soils procreation from consolidation test. The results from laboratory tests shows high ability on the enhancing in terms of reduction in plasticity index (greatly increased workability), reduction in compression ratio (CR), reduction in the Rebound (Swelling) ratio (RR), increase in the modulus of elasticity (Es). The change in moisture-density relationships resulting in lower maximum dry densities, higher optimum water content, and less variation of dry density from the maximum over a much wider range of water contents.

Using compression hosiery to prevent rebound swelling.

The management of chronic oedema often consists of a programme of compression bandaging to reduce swelling and improve skin changes and limb shape, followed by patient self-care management in compression hosiery. Occasionally, patients experience rebound swelling and require further episodes of bandaging. In such cases, a thorough assessment of the causes of the rebound swelling should be carried out so that they can be eliminated. By evidencing three case studies, this article demonstrates that Haddenham Custom Goldpunkt garments can be useful in preventing rebound swelling, making it a cost- and resource-effective method of managing stubborn chronic oedema and lymphoedema.

Rhinitis medicamentosa: Electron microscopic changes of human nasal mucosa

Prolonged application of nasal vasoconstrictors causes rhinitis medicamentosa (RM). Nasal obstruction is induced by rebound swelling when the decongestive effect has disappeared. The aim of this study was to demonstrate ultrastructural changes in RM. Tissue samples of inferior turbinates from 22 patients with RM and 10 patients without rhinitis were taken during nasal surgery. Ultrathin sections were investigated by using a transmission electron microscope (TEM). The TEM findings revealed severe epithelial damages such as loss of ciliated cells. In the subepithelial region, the vascular endothelium showed gaps and ruptures of basal lamina. RM is a drug-induced damage of human nasal mucosa. Loss and destruction of ciliated epithelial cells are the morphologic correlation of the disturbed mucociliary clearance. In addition, vascular endothelium revealed ultrastructural changes. This could be caused by an increased vascular permeability with consecutive interstitial edema. This study demonstrated new morphological aspects of rhinitis medicamentosa.

Ultrastrukturelle Veränderungen der Nasenschleimhaut des Menschen nach Abusus von topischen α-Sympathomimetika

Long-term abuse of decongestive nasal drops causes rhinitis medicamentosa due to cytotoxic and ciliary-toxic effects. Nasal obstruction is caused by rebound swelling when the decongestive effect has disappeared. The patient starts using nasal drops more frequently as a result of tachyphylaxis. Tissue samples from human inferior turbinates from 22 patients who had overused decongestive nose drops were taken during nasal surgery and preserved in phosphate-buffered paraformaldehyde or glutaraldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. The findings were photo-documented using a light- and transmission electron microscope. Biopsies from ten patients without chronic inflammation of the nasal mucosa were used as controls. The electron microscopic investigations revealed epithelium showing severe damage corresponding to regions with hyperplastic and metaplastic changes. Loss of ciliated cells was observed. Under a thick basal membrane, ultrastructural changes to the endothelial lining, such as openings and rupture of the basal lamina, were detected. Prominent endothelial cells were conspicuous. Rhinitis medicamentosa is a drug-induced injury to human nasal mucosa associated with the prolonged abuse of topical nasal decongestants. Loss and destruction of ciliated epithelial cells are the morphological correlation to the disturbance of mucociliary clearance. Endothelial cells of capillaries, in particular, revealed ultrastructural changes indicative of increased permeability with consecutive interstitial edema.

Rhinitis Medicamentosa

Rhinitis medicamentosa (RM) is a drug-induced, nonallergic form of rhinitis that is associated with prolonged use of topical vasoconstrictors, i.e. local decongestants. Symptoms are exacerbated by the preservative benzalkonium chloride (BKC) in the nasal preparations. Nasal stuffiness is caused by rebound swelling of the mucosa when the decongestive effect of the drug has disappeared. To alleviate this symptom, patients gradually start using larger doses of the vasoconstrictor more frequently. In many cases, the patient is unaware of the condition, thus entering a vicious circle of self-treatment. Careful questioning is required during consultation to establish diagnosis. The pathophysiology of the condition is unclear; however, vasodilatation and intravascular edema have both been implicated. Management of RM requires withdrawal of topical decongestants to allow the damaged nasal mucosa to recover, followed by treatment of the underlying nasal disease. Topical corticosteroids such as budesonide and fluticasone propionate should be used to alleviate rebound swelling of the nasal mucosa. Where possible, avoiding exposure to BKC is recommended.

Adverse Effects of benzalkonium chloride on the nasal mucosa: Allergic rhinitis and rhinitis medicamentosa

Prolonged, repeated use of nasal decongestants for symptomatic relief of allergic rhinitis often results in rhinitis medicamentosa (RM), a condition involving “rebound swelling” and additional congestion. Most decongestant sprays contain the preservative benzalkonium chloride (BKC), which causes toxic reactions in the nose, eyes, ears, and lungs, and may exacerbate the symptoms of allergic rhinitis. Recent studies demonstrate the effects of nasal sprays containing BKC or the decongestant oxymetazoline (OXY) in the development of RM. Using rhinostereometry, a technique that measures nasal mucosal swelling and nasal reactivity (with histamine challenge tests), prolonged use of OXY has been shown to induce nasal mucosal swelling and hyperreactivity. Sustained use of BKC alone induces nasal mucosal swelling and, in combination with OXY, BKC appears to have a long-term adverse effect on nasal mucosa. Its presence may also contribute to the RM resulting from overuse of decongestant sprays. Additional research is needed to confirm the deleterious effects of BKC in nasal products. However, these potential effects may be points of clinical differentiation in the treatment of allergic rhinitis and prevention of RM.

Rebound swelling of astroglial cells exposed to hypertonic mannitol.

Mannitol is widely used in anesthesia and critical care medicine. Although its clinical effects were originally attributed to osmotic dehydration of brain cells, other mechanisms have also been proposed. Osmotic dehydration of astroglial cells is opposed by powerful volume-regulating mechanisms that involve inward transport of electrolytes. These mechanisms have been studied previously by exposing cells to hypertonic saline gradients. Because of its potential clinical relevance, the volume response of astroglial cells exposed to hypertonic mannitol was investigated. Rat C6 glioma cells were cultured to confluence, and their volume behavior was observed by laser light scattering. After equilibration at physiologic temperature and pH, cells were abruptly exposed to hypertonic mannitol solutions. In separate experiments, C6 cells were exposed to hypertonic solutions containing radiolabeled mannitol, and its cellular uptake was determined. Hypertonic mannitol exposure produced initial cell shrinkage followed by rapid volume recovery and rebound swelling. The rebound swelling was similar in magnitude to the initial maximal shrinkage. For +40 mOsm and +70 mOsm mannitol challenges, mean volume recovery was 184+/-31% and 227+/-62%, respectively (where full recovery to baseline volume = 100%). Rebound swelling was substantially inhibited by furosemide. When exposed to mannitol in varying concentrations, uptake was linear, ranging from 82+/-7 nmol/mg to 406+/-26 nmol/mg protein. After 5 min, estimated intracellular concentrations of mannitol were similar to extracellular concentrations. Unlike hypertonic saline, hypertonic mannitol exposure produces rebound cell swelling. Cellular penetration of mannitol appears to account for much of this phenomenon. The clinical implications of these observations remain to be determined.

Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers

A randomized double-blind parallel study with 20 healthy volunteers was performed to research the effect of a preservative in a decongestant nasal spray on the development of rhinitis medicamentosa. Ten subjects received oxymetazoline nasal spray with benzalkonium chloride and the others used oxymetazoline nasal spray without the preservative three times daily for 30 days. Before starting the course of treatment and after its conclusion, recordings of the mucosal surface positions were made with rhinostereometry followed by histamine challenge tests. Symptoms of nasal stuffiness were estimated on visual analogue scales (0-100) in the morning and the evening just before using the nasal spray. After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray with benzalkonium chloride the mean rebound swelling was 1.1 mm and the estimated mean evening symptom score for nasal stuffiness was 43. In the group without benzalkonium chloride the corresponding variables were significantly less marked, with a mean rebound swelling of 0.5 mm (P < 0.05) and a mean evening symptom score of 25 (P < 0.05). The increase in histamine sensitivity in both groups was interpreted as a sign of nasal hyperreactivity. A new type of nasal spray bottle was used that has been shown to prevent bacterial contamination. In conclusion, the long-term use of benzalkonium chloride in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers.

Four-Week Use of Oxymetazoline Nasal Spray (Nezeril(R)) Once Daily at Night Induces Rebound Swelling and Nasal Hyperreactivity

A randomized double-blind parallel study with 20 healthy volunteers was performed to examine the effect of oxymetazoline nasal spray on the development of rhinitis medicamentosa. For 30 days, 10 subjects were given oxymetazoline nasal spray once daily at night and placebo in the morning and at noon, while the others used oxymetazoline nasal spray three times daily. Before and after the course of treatment, the mucosal surface positions were determined with rhinostereometry, followed by histamine challenge tests. In the morning and the evening just before use of the nasal spray, symptoms of nasal stuffiness were evaluated on visual analogue scales (0-100). After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray once daily at night, the mean rebound swelling was 0.8 mm (p < 0.01) and the estimated mean symptom score for nasal stuffiness in the evening was 43 (p < 0.05). In the group receiving the same nasal spray three times daily, the mean rebound swelling was 1.1 mm (p < 0.01) and the mean evening symptom score was 43 (p < 0.05). The finding of an increase in histamine sensitivity in both groups was taken to indicate nasal hyperreactivity. There was no significant difference in the investigated variables between the two groups. It is concluded that the risk of developing rebound swelling and nasal hyperreactivity remains, whether oxymetazoline nasal spray is used once or three times a day for 30 days.

Histamine Sensitivity in the Nasal Mucosa during Long-term Use of Xylometazoline in the Doubled Recommended Dose

It has been suggested that the severity of rhinitis medicamentosa is dependent on the length of time the drug has been used, on how frequently it is used, and on the amount administered. It has been reported that a 4-week use of oxymetazoline in the recommended dose induced a rebound swelling and an increased histamine sensitivity as a sign of rhinitis medicamentosa and nasal hyperractivity. In order to study the impact of an increased amount of vasoconstrictor on the histamine sensitivity, nine healthy subjects had xylometazoline nasal spray in the doubled recommended dose (1.0 mg/mL; 0.28 mL in each nostril three times daily) for 30 days. After 10 days on the drug the histamine sensitivity was slightly increased, and after another 20 days the sensitivity was significantly increased compared to that before the start of the medication (P &lt; 0.01). When comparing the results from this study with the corresponding ones from the oxymetazoline study, no difference in the histamine sensitivity was seen. One month after the medication was finished three subjects still had an increased sensitivity to histamine. It was concluded that the doubled recommended dose of xylometazoline did not further increase the elevated histamine sensitivity seen following vasoconstrictor used in recommended dose. The results also indicate that the increased histamine sensitivity was not caused by the preservatives. Finally, the subjects achieved a drug-induced non allergic nasal hyperreactivity (NANH) that in some subjects persisted for a long time.

Decongestion effect and rebound swelling of the nasal mucosa during 4-week use of oxymetazoline.

The aim of this study was to investigate whether long-term use of oxymetazoline induces a rebound swelling of the nasal mucosa and whether the decongestion effect is altered during medication. Eight healthy volunteers had oxymetazoline nasal spray (0.5 mg/ml; 0.1 ml in each nostril, three times daily) for 30 days and registrations of the mucosal surface positions were made using rhinostereometry. Compared to the registrations before the start of medication, no rebound swelling was registered after 10 days. After 30 days, however, a rebound swelling was registered in all subjects (p < 0.001). All of them, then, also reported nasal stuffiness. The decongested position of the nasal mucosa after one single dose of oxymetazoline was the same in the whole study. It is concluded that rhinitis medicamentosa develops after a relatively short time on oxymetazoline, even in healthy volunteers, and that the swelling probably is due to a vasodilatation rather than an edema. The study supports the recommendation that the drug should not be used over periods > 10 days.