[Early hypertrophic scar after surgery on the nasal region: value of long-acting corticosteroid injections]. / Hypertrophie cicatricielle précoce post-chirurgicale de la région nasale : intérêt des injections de corticoïde retard.

BACKGROUND: "Pincushioning" is a complication of post-surgical scarring following use of transposition flaps particularly when surgery is performed on the nasal region. The transposition flap technique is very useful for the repair of certain defects of the tip of the nose, the medial canthus or of the ala nasi. The aim of this study is to define the clinical characteristics of this scarring dystrophy, which we propose to call "early hypertrophy scarring", to clarify the nature thereof and to assess the efficacy of intralesional injection of corticosteroids at the first signs of hypertrophy. PATIENTS AND METHOD: A prospective, open, non-comparative, single-centre study examined the clinical and histological characteristics of early hypertrophy scarring and the effectiveness of therapy with one or two injections of corticosteroids performed on the 15th day post-operatively and optionally repeated at D45 depending on the outcome. From January 2011 to January 2013, 12 consecutive patients with early hypertrophy scarring were included (ten men and two women - mean age: 64 years). All had undergone surgery for basal cell carcinoma under local anaesthesia with one-stage repair by means of a rhombic flap or a bilobed flap located in the nasal area. Scars were injected strictly intra-lesionally with triamcinolone acetate (40 mg/1 mL) until whitening occurred. A single injection was performed in three cases of rhombic flap while a second injection was given at D45 in the remaining nine cases. RESULTS: Complete regression of the early hypertrophy scarring was obtained in ten of the 12 patients by D90. Incomplete regression was observed but with a marked improvement in the other two patients. DISCUSSION: Early hypertrophy scarring is distinguished by its clinical characteristics of hypertrophic or keloid scars. Biopsy performed in two cases showed the fibrous but non-fatty nature of early hypertrophy scarring. Biomechanical factors particular to the nasal region and the transposition flap technique could account for the early and excessive collagen production causing early hypertrophy scarring. Early injection of corticosteroids, which was consistently effective in our study, could represent a simple treatment for early hypertrophy scarring, thus avoiding surgical correction. These preliminary results in a small number of patients require confirmation by a comparative, multicentre, prospective controlled study.

Repeat percutaneous epicardial mapping and ablation of ventricular tachycardia: safety and outcome.

INTRODUCTION: Epicardial mapping and ablation of ventricular tachycardia (VT) has been increasingly performed. Occasionally additional ablation is necessary, requiring repeat percutaneous access to the pericardial space. METHODS AND RESULTS: We studied 30 consecutive patients who required a repeat epicardial procedure. We specifically examined the success and safety of repeat percutaneous pericardial access as well as the ability to map and ablate epicardial VT targets. Percutaneous pericardial access at a median of 110 days after the last procedure was successful in all 30 patients. Significant adhesions interfering with catheter mapping were encountered in 7 patients (23%); 6 had received intrapericardial triamcinolone acetate (IPTA) with prior procedures. Using blunt dissection with a deflected ablation catheter and a steerable sheath, adhesions were divided allowing for complete catheter mapping in 5 patients with areas of dense adherence compartmentalizing the pericardium in 1 patient and precluding ablation over previously targeted ablation site in the second. Targeted VT noninducibility was achieved in 27 (90%) patients including 7 patients with adhesions. No direct complications related to pericardial access or adhesions disruption occurred. One periprocedural death occurred from refractory cardiogenic shock in patient with LV ejection fraction of 10%. Another patient developed asymptomatic positive Haemophilus influenzae pericardial fluid cultures identified at second procedure, which was successfully treated. CONCLUSIONS: Repeat access can be obtained after prior epicardial ablation. Adhesions from prior procedures may limit mapping, but can usually be disrupted mechanically and allow for ablation of recurrent VT. IPTA may not completely prevent adhesions.

Identification and characterization of triamcinolone acetonide, a microglial-activation inhibitor.

Recent studies show that necrotic neuronal cells (NNC) activate microglia, thereby leading to neuronal cell death. This suggests that chemicals that inhibit microglia activation may be used as neuroprotective drugs. In this context, we screened a chemical library for inhibitors of microglia activation. Using a screening system based on a nitrite assay, we isolated two chemicals that inhibit nitric oxide (NO) release from activated microglia: triamcinolone acetonide (TA) and amcinonide. The half-maximal inhibitory concentrations (IC50) of TA and amcinonide for NO release inhibition were 1.78 nM and 3.38 nM, respectively. These chemicals also inhibited NNC-induced expression of the proinflammatory genes iNOS, TNF-α, and IL-1ß in glial cells. A study based on a luciferase assay revealed that TA attenuated NNC-induced microglia activation by blocking the NF-κB signaling pathway. In addition, TA protected cortical neurons in coculture with microglia from LPS/IFN-γ-induced neuronal cell death. In conclusion, TA may inhibit microglia activation and may protect neuronal cells from death induced by microglial activation.

Effectiveness of intramuscular corticosteroid injection versus placebo injection in patients with hip osteoarthritis: design of a randomized double-blinded controlled trial.

BACKGROUND: Recent international guidelines recommend intra-articular corticosteroid injections for patients with hip osteoarthritis who have moderate to severe pain and do not respond satisfactorily to oral analgesic/anti-inflammatory agents. Of the five available randomized controlled trials, four showed positive effects with respect to pain reduction. However, intra-articular injection in the hip is complex because the joint is adjacent to important neurovascular structures and cannot be palpated. Therefore fluoroscopic or ultrasound guidance is needed.The systemic effect of corticosteroids has been studied in patients with impingement shoulder pain. Gluteal corticosteroid injection was almost as effective as ultrasound-guided subacromial corticosteroid injection. Such a clinically relevant effect of a systemic corticosteroid injection offers a less complex alternative for treatment of patients with hip osteoarthritis not responsive to oral pain medication. METHODS/DESIGN: This is a double-blinded, randomized controlled trial. A total of 135 patients (aged > 40 years) with hip osteoarthritis and persistent pain despite oral analgesics visiting a general practitioner or orthopaedic surgeon will be included. They will be randomized to a gluteal intramuscular corticosteroid injection or a gluteal intramuscular placebo (saline) injection. The randomization will be stratified for setting (general practitioner and outpatient clinics of department of orthopaedics). Treatment effect will be evaluated by questionnaires at 2, 4, 6, and 12 weeks follow-up and a physical examination at 12 weeks. Primary outcome is severity of hip pain reported by the patients at 2-week follow-up. Statistical analyses will be based on the intention-to-treat principle. DISCUSSION: This study will evaluate the effectiveness of an intramuscular corticosteroid injection on pain in patients with hip osteoarthritis. Patient recruitment has started. TRIAL REGISTRATION: This trial is registered in the Dutch Trial Registry: number NTR2966.

[A comparative clinical study of the treatment of hypertrophic scars with either intralaesional steroid or silicone gel sheeting]. / A hypertrophiás hegek intralaesionalis szteroid és polisziloxán-tapaszos kezelésének összehasonlító klinikai vizsgálata.

The linear (or "surgical") hypertrophic scar is the most common type of pathologic scarring. There has been a steady increase in the number of patients with hypertrophic scars over the years due to the rising number of operative interventions altogether. However, the therapeutic protocols are not homogeneous and they show significant variations. 200 cases with hypertrophic scars were treated by the authors from April 2001 to March 2004. 24 patients were selected in the study from these cases; and two randomized groups were formed. Each group included 12-12 patients, who were treated with either intralaesional steroid or silicone gel sheeting. The therapeutic protocols were defined by the authors. The aim of this study was to compare and determine the roles of these two commonly used treatment options of hypertrophic scars. The authors present patient demographics; and analyze the results and outcome of the study. Both methods were efficient significantly, however intralaesional steroid therapy had a more rapid effect and it lasted longer than silicone gel sheeting. These results confirmed the role of these two treatment modalities in the protocols. The authors concluded that silicone gel sheeting is the first line, while intralaesional steroid is the second line treatment for primary linear hypertrophic scars. Based on the authors' experience, in recurrent linear hypertrophic scars, intralaesional steroid therapy is recommended in first line, because silicone gel sheeting was largely ineffective. Prospective randomized clinical trials should be needed to further clarify their role in the treatment protocols.

Investigations on the polymorphism and pseudopolymorphism of triamcinolone diacetate.

The glucocorticoide triamcinolone diacetate was investigated for polymorphism. Crystallization experiments in different solvents performed at room-temperature reveal that in most cases solvates has formed (form B) which are isotypic and which crystallize in the orthorhombic space group P2(1)2(1)2(1). In their crystal structure channels are formed in which the solvent molecules are located. In some other solvents the commercial available form A is the thermodynamic most stable form. On heating form A using differential scanning calorimetry (DSC) the compound melts at a peak temperature of 136 degrees C without any further polymorphic transformation. If the solvents are removed at higher temperatures using simultaneous differential thermoanalysis and thermogravimetry coupled to mass spectroscopy (DTA-TG-MS) the remaining residues are amorphous against X-rays because the compound melts directly after desolvation. If the desolvation process is investigated by DSC measurements the same is observed for most solvents but in some cases different peaks for desolvation and melting are observed. In this case a new modification can be isolated after removing the solvent (form C). If the solvent are removed in vacuum or by storage at room-temperature always the commercial available form A is obtained, whereas desolvation experiments at 80 degrees C indicate the formation of a further polymorphic modification (form D).

Glucocorticoid-induced elevation of serum high-density lipoprotein-cholesterol and its reversal by adrenocorticotropin in the rat.

The effect of administration of a high dose of glucocorticoid (triamcinolone) on serum lipids and lipoproteins was studied in rats. Changes in serum lipids, especially cholesterol, were most marked when 5 mg/kg body weight of triamcinolone was injected daily for 5 days. Serum lipoproteins were separated by ultracentrifugation followed by gel-filtration chromatography. Cholesterol distribution between apolipoprotein B-containing lipoproteins (very-low-density and low-density lipoproteins), high-density lipoprotein1 (HDL1), and HDL2 was determined after administration of triamcinolone with or without additional treatment with adrenocorticotropin (ACTH; Cortrosyn, 6 IU/rat). When triamcinolone was administered, cholesterol concentrations in HDL1 and HDL2 were elevated in a dose-dependent manner, but there was no significant change in apolipoprotein B-containing lipoprotein cholesterol levels. When ACTH was administered in combination with triamcinolone, the concentrations of all serum lipids except triacylglycerol were significantly lowered compared with rats treated with triamcinolone alone. HDL1-cholesterol concentration in serum was significantly (P less than 0.001) lowered from 69 +/- 13 mg/dl (mean +/- S.D.) in triamcinolone-treated rats to 36 +/- 4 mg/dl by the administration of ACTH plus triamcinolone. The additional administration of ACTH in triamcinolone-treated rats caused a slight, but significant, decrease in cholesterol concentration in apolipoprotein B-containing lipoproteins; however, HDL2-cholesterol level was not significantly affected, although there was a tendency for it to be lowered.

Corticosteroids suppress ectopic neural discharge originating in experimental neuromas.

Some injured sensory fibers ending in an experimental neuroma in the rat sciatic nerve discharge spontaneously. Furthermore, many become sensitive to a range of physical and chemical stimuli. The resulting afferent barrage is thought to contribute to paresthesias and pain associated with peripheral nerve injury. We report that the development of such ectopic neuroma discharge is largely prevented when the freshly cut nerve end is treated with any of 3 commercially available corticosteroid preparations including two in depot form, triamcinolone hexacetonide (Lederspan) and triamcinolone diacetate (Ledercort), and one in soluble form, dexamethasone (Dexacort). These corticosteroids also produce a rapid and prolonged suppression of ongoing discharge in chronic neuromas that have already become active. The kinetics of corticosteroid suppression of neuroma discharge suggest a direct membrane action rather than an anti-inflammatory action.

Inhibition of prostaglandin synthesis in brain of rat by dexamethasone: lack of effect of dexamethasone phosphate ester and various hormonal steroids.

The present study was designed in order to characterize the inhibitory effect of dexamethasone upon the synthesis of prostaglandins (PG) in the brain of the rat. Rats were treated with dexamethasone (20 mg/kg b.w.) and sacrificed 0-76 hr after administration of the drug. The rate of synthesis and release of PGE2 was followed by 1 hr of incubation of slices of cortex taken from these rats, in Krebs-Ringer solution. A significant inhibition occurred at 8 hr and maximal inhibition (45%) was attained at 16 hr after injection. A gradual increase in the rate of synthesis up to control values occurred between 24 and 76 hr. A dose-response study, at the range of 2-40 mg/kg, showed that a significant decrease was noted at 6 mg/kg and it was maximal (45% inhibition) at 20 and 40 mg/kg. Administration of dexamethasone-sodium-phosphate, as well as other synthetic glucocorticoids and various steroidal hormones (20 microM), failed to inhibit the biosynthesis of prostaglandins under the same experimental conditions. The effect of dexamethasone and dexamethasone phosphate on synthesis of PGE2 was also studied under in vitro conditions at 5 and 20 microM. When slices of cortex from intact rats were incubated for 1 or 2 hr in the presence of either dexamethasone or dexamethasone phosphate only dexamethasone was effective in inhibiting the synthesis of PGE2. The present results demonstrate that the inhibition of the synthesis of prostaglandins in brain by dexamethasone is both time- and dose-dependent. The lack of effect of closely related glucocorticoids demonstrate that the effect is highly specific to dexamethasone.

High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas.

BACKGROUND: Intralesional injection of corticosteroids is an effective treatment for tumors of the head and neck. Complications are rare but include permanent loss of vision. We designed a study to investigate the mechanism for this complication. METHODS: Three fellowship-trained pediatric ophthalmologists participated in the study in a nonmasked fashion. Four patients received 5 separate treatment sessions of an intralesional injection of a 50-50 mixture of triamcinolone diacetate (40 mg/mL) and betamethasone sodium phosphate and betamethasone acetate (6 mg/mL) into capillary hemangiomas. Injection pressure was obtained in real time using a cannula designed for this purpose. Maximum pressure, mean pressure, and volume of corticosteroid were measured from each injection. RESULTS: A total of 71 injections (range, 8-33 injections per patient) was performed. The total volume of corticosteroid ranged from 0.9 to 2.1 mL. In 63 of 71 injections, the maximum pressure exceeded 100 mm Hg (range, 18.65-842.18 mm Hg). Each surgeon produced injection pressures greater than the systemic arterial pressures of each patient. CONCLUSIONS: Injection pressures exceeding the systemic arterial pressures routinely occur during intralesional injections of corticosteroids into capillary hemangiomas. Experienced surgeons participating in a nonmasked protocol were unable to prevent high injection pressures of corticosteroid. A sufficient volume of corticosteroid injected at high injection pressure would account for the embolization of corticosteroid particles into the ocular circulation from retrograde arterial flow. We recommend limiting the volume of corticosteroid and performing indirect ophthalmoscopy on all patients receiving injections of long-acting corticosteroids into the orbit and periorbital soft tissue.

The effect of glucocorticoid treatment on denervated rat hemidiaphragm.

The degenerative process in phrenic nerve motor nerve terminals following nerve section was analyzed in rats that had previously been subjected to an intensive short term regimen of the steroid preparation triamcinolone. Morphological studies indicated that the onset time of degeneration was similar to that of untreated rats but less severe, and the time for maximal degenerative changes was increased. Concurrent to the preservation of motor nerve terminal structure under conditions of denervation, triamcinolone also induced myopathies in the diaphragm, the white muscle fibers being predominantly affected. Due to the structural aberrations of muscle, the indirect and direct twitch response of hemidiaphragms in triamcinolone treated rats was depressed. Data obtained from indirect post-tetanic potentiation (PTP) responses, however, did express the anatomical preservation of motor nerve terminals. These findings may add support to previous observations for the basis of effectiveness of the glucocorticoids in the treatment of neuromuscular disorders.

Glucocorticoid modification of spinal dopamine receptor activation by apomorphine.

The effects of an intensive short-term glucocorticoid (e.g. triamcinolone) regimen in cats have been studied on the actions of the dopamine (DA) receptor agonist apomorphine (APO) on spinal lumbar primary afferent excitability (dorsal root reflex or DRR) and monosynaptic reflex (MSR) transmission. Glucocorticoid dosing significantly decreased the APO-induced depression of the spinal DRR, but not the similar action of APO on the MSR. This complex effect of triamcinolone on spinal dopaminergic activation by APO may represent a differential action of glucocorticoid on two types of spinal DA receptors with one type, but not the other, undergoing partial desensitization.

Vitrectomy and internal limiting membrane peeling for myopic foveoschisis.

PURPOSE: Myopic foveoschisis is common in high myopia. We report results of a pilot study of vitrectomy for patients with myopic foveoschisis. DESIGN: Interventional case series. METHODS: In an institutional setting five patients with high myopia (six eyes), and who had progressive visual impairment presumably due to myopic foveoschisis were studied. No eyes had a macular hole preoperatively based on optical coherence tomography (OCT). We performed vitrectomy including vitreous cortex removal, internal limiting membrane (ILM) peeling, and gas tamponade. Patients were followed for at least 6 months. Best-corrected visual acuity (BCVA), OCT. Scanning laser ophthalmoscope (SLO) microperimetry was examined in three eyes. RESULTS: The foveal detachment resolved completely in five eyes and partially in one eye. No serious complications developed including macular hole formation or retinal detachment; BCVA improved more than two lines in all eyes (100%) 6 months postoperatively (P <.01); SLO microperimetry showed smaller scotoma compared with preoperatively and stabilized fixation. CONCLUSIONS: Vitrectomy with vitreous cortex removal, ILM peeling, and gas tamponade could be useful to treat myopic foveoschisis in highly myopic eyes. Because the natural course of the disease is not well-understood, further study should establish indications for this surgery.

Experimental and clinical observations of the intraocular toxicity of commercial corticosteroid preparations.

We tested the vehicles of six different commercially available depot corticosteroids (Celestone Soluspan, Depo-Medrol, Decadron, Decadron L. A., Aristocort, and Kenalog) for possible toxicity when injected intravitreally. When tested on rabbit eyes, the Celestone Soluspan and the Depo-Medrol vehicles caused remarkable retinal degeneration with preretinal membrane formation or cataracts in their standard concentrations. Three other vehicles (Decadron and Decadron L. A.) caused localized retinal degeneration in twice the standard concentration. Thus, toxic effects can be caused by preservatives or inadequate osmolarity of the vehicles alone. The development of proliferative vitreoretinopathy in some cases of injections of intraocular depot corticosteroid can be explained by retinal necrosis and repair processes caused by these vehicles.

Subtenon's depot corticosteroid injections in patients with a history of corticosteroid-induced intraocular pressure elevation.

PURPOSE: To determine whether a history of intraocular pressure elevation from local corticosteroid administration could predict subsequent intraocular pressure elevation after posterior subtenon's corticosteroid injection. METHODS: A retrospective review was performed of 64 consecutive patients (64 eyes) receiving posterior subtenon's corticosteroid injection. Patients were categorized as either historical corticosteroid responders or nonresponders based on intraocular pressure response to topical corticosteroid drops in the same eye or to previous posterior subtenon's corticosteroid injection of the fellow eye. Historical responders were defined as having a relative intraocular pressure increase of 5 mm Hg and absolute intraocular pressure greater than 24 mm Hg with an anatomically open angle. Relative risk of intraocular pressure elevation was evaluated based on historical response and presenting diagnosis. RESULTS: Nine eyes were historical responders, and 55 eyes were historical nonresponders. A higher rate of recurrent intraocular pressure elevation developed in historical responder eyes (4 of 9, 44%) compared with nonresponders (7 of 55, 13%) after posterior subtenon's injection (P = .04, Fisher's test; P = .07, Kaplan-Meier analysis). Historical responders with uveitis were at significantly higher risk of intraocular pressure elevation than nonresponders without uveitis (hazard ratio = 10.8, P = .04, Cox proportional hazards). All but one eye that developed intraocular pressure elevation from posterior subtenon's injection was adequately controlled with topical antiglaucoma therapy. CONCLUSION: In nonglaucomatous eyes, a previous history of corticosteroid-induced intraocular pressure elevation is a relative, not absolute, contraindication to posterior subtenon's corticosteroid injection, because the risk of intraocular pressure elevation is not absolute, and because it can usually be well controlled with topical antiglaucoma therapy.

Modulation of interferon synthesis with the drugs applied in bronchial asthma.

Investigations were carried out on 28 patients with nonatopic bronchial asthma treated with glycocorticosteroids or antibiotics and on 15 patients with atopic bronchial asthma treated with Alavac S vaccine. Leukocytes isolated from these patients by the method of Mogensen and Cantell were induced with Newcastle disease virus for interferon production, IFN was tested in the culture of human fibroblasts (HAT). The production of leukocytic IFN in glycocorticosteroids- and antibiotics-treated patients was shown to increase. On the contrary, the leukocytes from the patients 3 months treated with Alavac S exhibited suppressed production of the interferon.

Clinical classification as a predictor of therapeutic outcome after cervical epidural steroid injection.

A retrospective analysis was done on 100 patients who had received cervical epidural steroid injections for neck pain and cervical radiculopathy to identify the predictors of outcome after such treatment. Potential predictors of outcome were assessed individually and then simultaneously with a multiple-regression model. Patients with radicular symptoms and signs had the best pain relief in contradistinction to those with axial (neck) pain. A clinical classification model predicting the outcome and an algorithm for the use of such injections in the treatment of cervical radiculopathy were developed.

Saphenous nerve entrapment at the adductor canal.

A retrospective study of 30 patients who met the clinical criteria for saphenous nerve entrapment at the adductor canal is described. Patients experienced symptoms, usually anterior knee pain, for an average of 36 +/- 7 months. Each patient received an average of 1.9 +/- 0.4 saphenous nerve blocks at the adductor canal during treatment. Baseline pain level (measured by the visual analog scale) was 6.4 +/- 0.3. Final pain level at followup was significantly decreased (2.8 +/- 0.5, P less than 0.001). Eighty percent of patients had improved after a series of blocks. Age, medications taken, number of blocks performed, and length of followup were unrelated to outcome. Length of symptoms did significantly correlate with final pain level (r = 0.39, P less than 0.05). The diagnosis of this syndrome, description of the saphenous nerve block at the adductor canal, and the possible etiology are presented.

Synthesis and pharmacological evaluation of new topical anti-inflammatory steroids.

The purpose of this research was to develop new topical steroid derivatives showing reduced systemic effects. Pregna-16 alpha,17-carboxycyclic acetal derivatives have been recently synthesized by reacting triamcinolone with methyl acetylalkanoate in the presence of a catalytic amount of perchloric acid. In testing for the anti-inflammatory activity of the compounds, rat cotton-pellet granuloma inhibition bioassay and mouse croton-oil-induced ear oedema inhibition bioassay were employed. One of the synthesized compounds, (22R)-9 alpha-fluoro-11 beta,21-dihydroxy-3,20-dioxo-16 alpha, 17-(methyl, methoxycarbonylmethyl)methylenedioxy-1,4-pregnadiene (I), showed more or less the same activity as shown by prednisolone in the granuloma inhibition test. However, compound I showed higher activity in the ear oedema inhibition test when applied topically (ID50 = 0.002 mg), as compared to prednisolone (ID50 = 0.006 mg) and triamcinolone (ID50 = 0.026 mg). When compound I was applied to mice, and thymus involution was measured for judging systemic effects, it was found that compound I did not show any significant thymus involution up to 0.1 mg/mouse (systemic administration) and 0.5 mg/mouse (topical administration). Because of its significantly reduced systemic effects, this compound is a promising topical anti-inflammatory steroid.