Search

Summary Objectives The present study was conducted to study the efficacy of intralesional steroid (ILS) injection in small benign vocal fold lesions and compare the outcomes with microlaryngeal surgery in terms of improvement in symptoms and reduction in lesion size. Methods The current randomized control trial was conducted in the Department of Otolaryngology at the Postgraduate Institute of Medical Education and Research in Chandigarh between 2014 and 2015. The clinical diagnosis was based on appearance of the lesion during endoscopy and the mucosal vibration pattern. Subjects with lesions of size less than or equal to 5 mm were included. Results A total of 29 subjects were included in the study and 15 (nine men and six women) of them were randomized to receive ILS injection. Fourteen (13 men and one woman) were randomized to the second group to receive initial microlaryngeal surgery. We noted significant reduction in the size of the lesion among subjects undergoing ILS injection at 12 weeks (1.11 + 1.45 mm) as compared to baseline (2.63 + 1.28 mm) with no recurrence. Conclusions ILSs are effective in reducing size of lesion and also improve acoustic parameters, perceptual analysis, and grade of dysphonia in patients presenting with small benign vocal cord lesions.

Study objective Migraine patients continue to report headache during the days and weeks after emergency department (ED) discharge. Dexamethasone is an evidence-based treatment of acute migraine that decreases the frequency of moderate or severe headache within 72 hours of ED discharge. We hypothesize that intramuscular methylprednisolone acetate, a long-acting steroid that remains biologically active for 14 days, will decrease the number of days with headache during the week after ED discharge by at least 1 day compared with intramuscular dexamethasone. Methods We conducted a randomized, blinded clinical trial comparing intravenous metoclopramide at 10 mg+intramuscular dexamethasone at 10 mg with intravenous metoclopramide at 10 mg+intramuscular methylprednisolone acetate at a dose of 160 mg for patients presenting to 2 different EDs with moderate or severe migraine. Outcomes were assessed by telephone with a standardized instrument. The primary outcome was number of days with headache during the week after ED discharge. Secondary outcomes were complete freedom from headache, without the necessity of additional headache medication for the entire week after ED discharge, and medication preference, as determined by asking the patient whether he or she would want to receive the same medication again. Results One hundred nine patients received dexamethasone and 111 received methylprednisolone acetate. We obtained primary outcome data from 101 dexamethasone patients and 106 methylprednisolone acetate patients. Dexamethasone patients reported 3.0 headache days and methylprednisolone acetate 3.3 headache days (95% confidence interval for rounded mean difference of 0.4 days: –0.4 to 1.1). Of 107 dexamethasone patients with analyzable data, 10 (9%) reported complete freedom from headache at 1 week versus 6 of 110 (5%) methylprednisolone acetate patients (95% confidence interval for difference of 4%: –3% to 11%). In the dexamethasone group, 76 of 101 (75%) patients would want the same medication again versus 75 of 106 (71%) of methylprednisolone acetate patients (95% confidence interval for difference of 4%: –8% to 17%). Other than injection site reactions, which were more common in the methylprednisolone acetate group, there were no substantial differences in frequency of adverse events. Conclusion Methylprednisolone acetate does not decrease the frequency of post-ED discharge headache days compared with dexamethasone. Most migraine patients are likely to continue to experience headache during the week after ED discharge.

Objective: Greater occipital nerve (GON) block is a treatment option applied for a variety of primary headache disorders. Although a patient's body position is known to have an impact on the effect of local anaesthetics, this has not before been investigated for patients undergoing GON block. Therefore, the clinical effectiveness of either a sitting or supine position was assessed.\ud \ud Patients and Methods: This evaluative prospective study took place in a single neurology department in the UK. Baseline and follow-up data were collated during standard clinic consultations for 95 consecutive patients who underwent GON block and follow-up consultations for treatment-refractory headache disorder. The GON block procedure was identical for all patients in terms of constitution of the applied medication and volume injected (lidocaine hydrochloride 20 mg and methylprednisolone acetate 80 mg in 2 ml vial). Directly afterwards, patients opted to either sit up (n = 34) or lie down (n = 61) for ten minutes.\ud \ud Results: Twenty-seven patients (44%) reported substantial benefit and 17 (28%) complete benefit (pain freedom) for a median duration of 70 days and 84 days in the 'supine' group, compared with 10 (29%) substantial and 6 (18%) complete benefit (pain freedom) for a median duration of 25 days (substantial) and 119 days (complete) in the 'sitting' group. Overall, a supine position results in a longer overall post-GON block headache-free period (p-value 0.007) and median relief score (p-value 0.017) compared to a sitting up position, as determined by Mann-Whitney U-test. Backward multiple linear regression analysis showed that the chronicity of the patient's condition is negatively associated (beta -0.24, p-value 0.024) and the post-GON block patient position is positively associated (beta 0.25, p-value 0.018) with the achieved headache-free period. Apart from variation in baseline headache characteristics, the 'sitting' and 'supine' cohorts did not significantly differ in terms of other clinical parameters and patient demographics.\ud \ud Conclusions: Placing a patient in a supine position following a GON block procedure for headache may significantly improve the resulting clinical effectiveness of this treatment. Further research, through a prospective, multi-centre, randomised, controlled trial, is indicated to determine if the initial positive observations in this present pragmatic evaluation can be confirmed.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that may progress to femoral head collapse and subsequently, degenerative arthritis. Although injection of bone marrow-derived mononuclear cells (BMMCs) is often performed with core decompression (CD) in the early stage of ONFH, these treatments are not always effective in prevention of disease progression and femoral head collapse. We previously described a novel 3D printed, customized functionally-graded scaffold (FGS) that improved bone growth in the femoral head after CD in a normal healthy rabbit, by providing structural and mechanical guidance. The present study demonstrates similar results of the FGS in a rabbit steroid-induced osteonecrosis model. Furthermore, the injection of BMMCs into the CD decreased the osteonecrotic area in the femoral head. Thus, the combination of FGS and BMMC provides a new therapy modality that may improve the outcome of CD for early stage of ONFH by providing both enhanced biological and biomechanical cues to promote bone regeneration in the osteonecrotic area.

Aim of the work: To evaluate the efficacy of intra-articular steroid injection of the shoulder joint with exercises in the management of patients with adhesive capsulitis and to compare glenohumeral (GH) versus subacromial subdeltoid (SASD) ultrasound-guided approaches. Patients and methods: Forty patients with adhesive capsulitis were randomly divided into 2 groups according to injection approach. Patients received ultrasound-guided intra-articular injection methylprednisolone acetate (40 mg) and 1 ml 2% lidocaine followed by exercise for 12 weeks. Visual analog scale (VAS) for pain, the shoulder pain and disability index (SPADI) and active range of motion (ROM) were assessed before and 12 weeks post-injection. Results: The mean age of the patients was 47.3 ± 8.7 years with 12 females and 8 males in each group. After injection, there was a significant improvement of pain (VAS) and SPADI in both groups (p

In a randomized, double-blind, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40 mg methylprednisolone acetate (MP) administered 1 week before total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥5 on a numeric rating scale during walk) and sensitization (pressure pain threshold 250 kPa), aged 50 to 80 years and scheduled for primary unilateral TKA under spinal anaesthesia were included. The primary outcome was the proportion of patients with moderate/severe pain during a 5-m walk test 24 hours postoperatively. Secondary outcomes included pain at 48 hours, during the first 14 days, sensitization (quantitative sensory testing with pressure pain threshold and wind-up from temporal summation), and inflammatory changes (systemic C-reactive protein, intra-articular interleukin [IL]-6). No difference in the proportion of patients with moderate/severe pain was found between MP/placebo groups at 24 hours (67% and 74%, χPeripherally driven inflammatory pain and nociceptive changes before TKA has been suggested to be a cause for increased acute postoperative pain. However, preoperative intra-articular MP in patients with high pain osteoarthritis and sensitization did not reduce acute post-TKA pain or sensitization despite a preoperative reduction of intra-articular inflammatory markers.

Arthroscopic rotator cuff (RC) repair incorporates suture anchors to secure torn RC tendons to the greater tuberosity (GT) bone. RC repair strength depends on the anchor-bone interface and on the quality of the GT. We evaluated the effect of single and multiple corticosteroid injections on the pullout strength of suture anchors.Fifty rats were divided into those receiving saline solution injection (control group), a single methylprednisolone acetate (MTA) injection (MTA1 group), or 3 once-weekly MTA injections (MTA3 group). Rats were killed humanely at 1 or 4 weeks after the last injection. A mini-suture anchor was inserted into the humeral head through the GT. Specimens were tested biomechanically.At 1 week after the last injection, the mean maximal pullout strength was significantly reduced in the MTA1 group (63.5%) and MTA3 group (56%) compared with the control group (P .05 for both). Mean stiffness decreased significantly in both treatment groups compared with controls (P .05). At 4 weeks after the last injection, there was a significant increase in the mean maximal pullout strength after single and triple MTA injections compared with values recorded at the 1-week time point (P .05). At 4 weeks, the mean maximal pullout strength after a single MTA injection was 92.8% of the pullout strength measured in the control group.We showed a significant detrimental effect of corticosteroid exposure on the pullout strength of a suture anchor at 1 week. However, this effect was transient and resolved within a relatively short period. These findings indicate that a waiting period is required between subacromial corticosteroid injection and RC repair surgery that involves the use of suture anchors.

Triamcinolone hexacetonide (TH), triamcinolone acetonide (TA), and methylprednisolone acetate (MPA) are commonly used intra-articular steroid preparations. Studies suggest that intra-articular TH is more efficacious than MPA and TA in chronic inflammatory arthritis. However, it is unclear which of the latter two preparations has better efficacy. Thus, we compared intra-articular knee injections of MPA and TA in patients with chronic inflammatory arthritis.This double-blind, randomized controlled trial included patients with rheumatoid arthritis or spondyloarthritis with an acutely swollen knee joint (≥1 week,24 weeks). They were randomly assigned (1:1) to intra-articular knee injection with MPA or TA (80 mg, 2 mL of each). Evaluations were performed at 4, 12, and 24 weeks. Primary outcome was time to relapse (Kaplan-Meier) over 24 weeks, with relapse defined as return to baseline pain or swelling ≥1 week. Secondary outcomes were change in pain and swelling (using a numerical rating scale), range of movement, and occurrence of adverse effects. Primary analysis was intention to treat, with last observation carried forward.One hundred patients (89 with rheumatoid arthritis) were randomly assigned in equal numbers to the MPA and TA groups. Nine patients relapsed in each group over 24 weeks. The mean time to relapse was not significantly different between the MPA and TA groups (20.8 [95% CI, 18.8-22.7] weeks and 20.9 [95% CI, 19.0-22.8] weeks, respectively; P = 0.9; hazard ratio = 1.0 [95% CI, 0.4-2.5]). In both groups, there was a significant decline in pain and swelling scores at all visits (P0.001); however, there were no significant intergroup differences. At 24 weeks, mean change in pain in the MPA (-4.4 [3.1]) and TA groups (-3.9 [2.8]) was not significantly different (P = 0.46). No infection, hematoma or hypopigmentation occurred in any patient. In addition, no significant intergroup differences were found in joint swelling, range of movement, modified (28 joint) Disease Activity Score using 3 variables, or Health Assessment Questionnaire over 24 weeks.No significant differences were found in efficacy between intra-articular knee injections with MPA and TA in these patients with chronic inflammatory arthritis. However, results need to be extrapolated cautiously because of the small sample size. Three-quarters of the patients remained relapse free at 24 weeks. Clinical Trials Registry of India (www.ctri.nic.in) identifier: CTRI/2015/09/006187.

Summary Background/Objective The purpose of this study was to evaluate supraspinatus tenocyte viability and metabolism in explants exposed to various local anaesthetics and corticosteroids. Our hypothesis was that the tendons exposed to these common injectates would have significantly decreased cell viability and metabolism compared with controls. Methods Supraspinatus tendon explants were obtained from dogs, placed in a culture media, and randomly assigned to one of the following groups: culture media only (control), 1% lidocaine, 0.5% lidocaine, 0.25% bupivacaine, 0.125% bupivacaine, 0.0625% bupivacaine, betamethasone acetate (5 mg), methylprednisolone acetate (40 mg), or triamcinolone acetonide (40 mg). Cell viability was determined on Days 1 and 7 after culture treatment using calcein AM (live cell) and Sytox Blue (dead cell) stains. Tissue metabolism was assessed on Days 1 and 7 using the resazurin blue metabolic assay. Significant differences were evaluated using a one-way analysis of variance with Tukey post hoc analysis. Results Compared with the controls, there were significant decreases in cell viability noted at Days 1 and 7 in tenocytes exposed to 1% lidocaine, betamethasone, and methylprednisolone. Significant decreases in cell metabolism were also noted at Days 1 and 7 in those groups. Treatment with 0.125% bupivacaine, 0.0625% bupivacaine, and triamcinolone demonstrated no decrease in cell viability or metabolism when compared with controls at any time point. Conclusion This data confirms that peritendinous injection of commonly used local anaesthetics and corticosteroids results in significant supraspinatus tenotoxicity in vitro. Further in vivo studies are required before making definitive clinical recommendations.

Rationale Allergic contact dermatitis (ACD) is a classic delayed hypersensitivity reaction commonly associated with corticosteroids that can rarely manifest as a delayed rash following systemic administration. Methods A 50-year old woman developed local edema and delayed spreading rash following interarticular injection with dexamethasone and methylprednisolone acetate (MA). 6-months following this intradermal skin testing (IDST) was positive to MA and methylprednisolone sodium succinate, and IDST and patch test negative to other corticosteroids. She tolerated dexamethasone challenge. Cells were isolated from 4-mm punch biopsies from 48-hour positive IDST and unaffected skin with liberase digestion and sorted on CD3. scTCR and scRNA-seq were performed using plate-based assays (Smart-seq-2). Data was filtered using Seurat and analysed with Visual Genomics Analysis Studio (VGAS) software. Results Histopathology showed a superficial perivascular dermatitis with epidermal spongiosis in keeping with ACD. T-cells were 18x more prevalent in affected skin and those from both affected and unaffected sites were predominantly CD8+ T-cells that expressed CD45RO and polyclonal TCR alpha beta. Differentially expressed genes (DEG) in T-cells from affected skin reflected homing (CCR7,S1PR1), T-cell activation and proliferation (TNFRS9, GRAP2, ZYG11A, ZHX1), T-cell effector differentiation (IL-21R), and stress survival (EEF1A1, IFI6) without representation of markers of T-cell residency (ITGAE) or regulation. Conclusions We demonstrate insights into the immunopathogenesis of drug-induced ACD by showing that IDST+ methylprednisolone associated ACD is corticosteroid-specific and associated with a polyclonal population of primarily CD45RO+ memory CD8+ T-cells showing upregulation of markers of homing, T-cell activation, proliferation and differentiation but lacking markers of T-cell residency and regulation.

The objective of this study was to improve the therapeutic efficacy of methylprednisolone acetate (MPA) in the treatment of rheumatoid arthritis (RA) by incorporating the drug into the hydroxyapatite (HAp) nanoparticles. The nanoparticles were synthesized using a chemical precipitation technique and their size and morphology were evaluated by dynamic light scattering and scanning electron microscopy (SEM). The solid-state behavior of the nanoparticles was also characterized by operating X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The Brunauer–Emmett–Teller and Barrett–Joyner–Halenda N2 adsorption/desorption analyses were also performed to determine the surface area, Vm (the volume of the N2 adsorbed on the one gram of the HAp when the monolayer is complete) and the pore size of the samples. Furthermore, the therapeutic efficacy of the prepared nanoformulation on the adjuvant induced arthritic rats was assessed. HAp mesoporous nanoparticles with a particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 44.53% were obtained. The specific surface area of HAp as well as the Vm values were decreased after the drug loading process. The nanoformulation revealed the slower drug release profile compared to the pure drug. The MTT assay indicated that the MPA-loaded nanoparticles had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines compared to the pure drug. Interestingly, the in vivo study confirmed that the drug-loaded nanoparticles could considerably decrease the paw volume and normalize the hematological abnormalities in the arthritic rats.

Lacidipine is a potent dihydropyridine calcium channel blocker used for management of hypertension and atherosclerosis. The drug has low and fluctuating oral bioavailability owing to its extensive hepatic first-pass metabolism and reduced water solubility. Accordingly, this work aimed at overcoming the aforementioned challenges through the formulation of intranasal nano-sized lacidipine glycerosomes. Box-Behnken was successfully employed for the formulation and in vitro optimization of the glycerosomes. Statistical analysis revealed that cholesterol concentration exhibited a significant effect on the vesicle size, while Phospholipon® 90G and glycerol concentrations exhibited significant effects on both entrapment efficiency and deformability index. The optimized formulation showed spherical shape, good deformability, vesicular size of 220.25 nm, entrapment efficiency of 61.97%, and enhanced ex vivo permeation by 3.65 fold compared to lacidipine suspension. Confocal laser scattering microscope revealed higher penetration depth via nasal mucosa for rhodamine labelled glycerosomes (up to 60 µm) in comparison to rhoadamine dye solution (26 µm). In addition, the optimized lacidipine glycerosomes caused significant reduction in methylprednisolone acetate-induced hypertension in rats for up to 24 h in comparison to oral drug suspension. Histopathological assessment showed intact nasal mucosal epithelial lining with no signs of inflammation or necrosis confirming the safety and tolerability of the proposed glycerosomes. The declared results highlights the potential of utilizing the proposed glycerosomes as safe and effective platform for intranasal delivery of lacidipine.

Background Corticosteroids have been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, whether inhaled corticosteroids (IC) alone have similar effects with systemic corticosteroid (SCS) is still unclear. Objectives To compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of AECOPD. Methods 30 AECOPD patients were randomly divided into two group. Budesonide group (15 cases) were treated with inhaled budesonide (3 mg Bid); methylprednisolone group (15 cases) were treated with systemic methylprednisolone (methylprednisolone acetate injectable suspension 40 mg Qd for three days and then methylprednisolone tablets 8 mg Bid). Observe symptoms, lung function, blood gas analysis and adverse effects of the patients in two groups. Peripheral blood samples were collected before and after treatment for 1 day, 4 days and 7 days. Interleukin-8 (IL-8) and TNF-α levels were determined by an enzyme linked immunosorbent assay (ELISA). Hs-CRP levels were detected by automatic biochemical analyzer. Western blotting was used to determine histone deacetylase 2 (HDAC2) protein expression. Measurements and main results Symptoms, pulmonary function and blood gas analysis were significantly improved after treatment in the two groups (P 0.05). There were no significant differences of IL-8, TNF-α and hs-CRP levels in the two groups (P > 0.05). Besides, the levels of HDAC2 protein expression before treatment were significantly lower comparing to that after treatment for 4 and 7 days. Incidence of adverse events (heart rate, blood pressure, glycemic , sleep condition, gastrointestinal symptoms) in budesonide group was lower than methylprednisolone group ( P Conclusions Inhaled budesonide and systemic methylprednisolone have the same effects on systemic inflammation of AECOPD. Inhaled corticosteroid alone could instead systemic corticosteroid in AECOPD treatment.

Aim To evaluate the feasibility and efficacy of ultrasound guidance technique for the treatment of meralgia paresthetica (lateral femoral cutaneous neuropathy). Methods 25 patients (10 males and 15 females); age 17–68 years; with meralgia paresthetica are diagnosed clinically by electromyography. A needle was inserted targeting the LFCN with ultrasound guidance, treatment with perineural injection of 2 mL of methylprednisolone acetate (40 mg/mL) and 8 mL of mepivacaine, 2%, under ultrasound guidance was performed. Main outcome measurements included the technical success of the procedure, regarding relief of symptoms (pain, burning sensation, and paresthesia) and change in the quality of life. Results Successful nerve block of the LFC nerve was achieved in 24 patients while 1 patient remained with mild VAS after third injection which disappeared two months later. Three patients underwent one injection, 6 two injections and 16 three injections with intervening period of 2 weeks between the first and second injections and one month between the second and third. Conclusions Ultrasound-guided perineural injection of the LFC nerve is quick, simple, economical, and effective in treatment of meralgia paresthetica.

Purpose To compare the corticosteroid injection (CSI) with or without thumb spica cast (TSC) for de Quervain tendinitis. Methods In this prospective trial, 67 eligible patients with de Quervain tenosynovitis were randomly assigned into CSI + TSC (33 cases) and CSI (34 cases) groups. All patients received 40 mg of methylprednisolone acetate with 1 cc lidocaine 2% in the first dorsal compartment at the area of maximal point tenderness. The primary outcome was the treatment success rate, and the secondary outcome was the scale and quality of the treatment method using Quick Disabilities of Arm, Shoulder and Hand and visual analog scale scores. Results The groups had no differences in mean age, sex, and occupation. The visual analog scale and Quick Disabilities of the Arm, Shoulder and Hand scores were similar in both groups before the treatment. The treatment success rate was 93% in the CSI + TSC group and 69% in the CSI group. Although both methods improved the patients' conditions significantly in terms of relieving pain and functional ability, CSI + TSC had a significantly higher treatment success rate. Conclusions The combined technique of corticosteroid injection and thumb spica casting was better than injection alone in the treatment of de Quervain tenosynovitis in terms of treatment success and functional outcomes. Type of study/level of evidence Therapeutic II.

Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles.

Introduction/Background Myofascial pain syndrome (MPS) is a frequent entity in clinical practice and is characterized by the presence of trigger points, limitation of joint mobility and neurological symptoms. The main purpose of this work was to evaluate the results obtained by perform an ultrasound-guided needling of the trapezius and levator scapulae muscles with simultaneous injection of steroids and local anesthetics, in the pain intensity and interference in daily life and the subjective benefits in patients with cervical MPS. Material and method Prospective longitudinal study, including patients with clinical diagnosis of unilateral or bilateral cervical MPS refractory to the conventional rehabilitation program, submitted to treatment during the year 2017. The technique included to pepper the trigger point with a fanlike manner under ultrasound guidance, using a 22G needle with simultaneous injection of 2% lidocaine and methylprednisolone acetate 40 mg/mL. A sociodemographic questionnaire, the pain numerical rating scale (NRS) and the brief pain inventory (BPI) were applied prior and 1 month after the procedure. In this last evaluation, a Likert scale was also applied to evaluate the subjective benefits. Results Eighteen patients were included, 82% female, with a mean of 54 years (SD = 8.2). No adverse effects were recorded. There was a statistically significant and clinically relevant reduction in the score obtained in the NRS (2.9, P Conclusion The results presented in this study show the importance of ultrasound-guided needling procedures in the treatment of myofascial pain and, at least, it short-term efficacy on reliefing pain, particularly in refractory cervical MPS.

September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection.

This Commentary highlights the article by Ritter et al. that reported the pathology associated with the recent fungal outbreak associated with contaminated methylprednisolone acetate injections.

Running in minimalist shoes continues to increase in popularity and multiple mainstream shoe companies now offer minimalist shoes. While there is no evidence that traditional running shoes prevent injuries, there are concerns that the designs of minimalist shoes may increase injury risk. However, reports of injuries in runners wearing minimalist shoes are rare. We present three injuries occurring in runners that were wearing minimalist shoes at the time of injury. All three of the runners switched immediately to the minimalist shoes with no transition period. We recommend that any transition to minimalist shoe gear be performed gradually. It is our contention that these injuries are quite common and will continue to become more prevalent as more runners change to these shoes.

Objective To investigate the significance of bone mineral changes in the pathogenic process of steroid-induced osteonecrosis in rabbits. Methods Seventy adult female Japanese White rabbits were randomly divided into five groups. Animals in steroid group received an intramuscular injection of methylprednisolone acetate (4 mg/kg) once a week, and killed in four different time after first treatment. Animals in control group received an intramuscular injection with the same volume of normal saline, while 150 kU penicillin was injected twice a week for preventing infection in all groups. The contents of serum calcium (Ca) and phosphorus (P) were determined and the bone mineral densities of the femoral head and neck were measured at the 2nd, 4th, 8th and 10th weeks after first treatment. Meanwhile the general condition such as weight, spirit and hair of rabbits was observed. Results Compared with the control group, the weight of rabbits in steroid group lost since the first week, and progressively aggravated; the bone mineral density of the femoral head and neck was lowered since the 2nd and 4th week respectively ( P P P P P Conclusion Osteonecrosis appears in rabbits shortly after corticoids are first administered, and osteonecrosis in rabbits is chronologically associated with the onset of hypocalcaemia, hypophosphatemia and lowered bone mineral density. Steroid-induced osteonecrosis may be relevant to bone mineral loss and density lowering of the femoral head and neck.

An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

Purpose To evaluate the long-term efficacy of combined radiofrequency (RF) neurotomy and steroid nerve block in patients with lumbar facet joint arthropathy. Materials and Methods Combined RF neurotomy and steroid nerve block was performed in 34 patients with chronic paravertebral low back pain. The diagnosis was confirmed by comparative double diagnostic block of the medial branch with bupivacaine and lidocaine. Under fluoroscopy, RF thermal ablation of the medial branch was performed (at RF needle tip temperature 85°C for 90 seconds), three times for each target nerve. At the end of the procedure, 20 mg of methylprednisolone acetate (sustained-release preparation) was infiltrated on each ablated nerve. Outcome variable was the degree of improvement in pain using visual analog scale (VAS) and numerical rating scale (NRS). Improvement in the quality of life was assessed using the Roland-Morris (RM) questionnaire. The procedure was repeated in cases of unbearable pain (>5 VAS score). Results Patients had a mean VAS score of 8.6 before the procedure. Thereafter, VAS score was 0.91 immediately after the procedure and 3.0, 2.8, 3.7, and 3.6 at 1 month, 2 months, 6 months, and 1 year. NRS showed pain relief after the procedure of 85%, 65%, 78%, 62%, and 59.5% at the same time points. RM score was 18 before the procedure, 7.6 at 6 months after the procedure, and 8.5 at 1 year after the procedure. No major complication was noted except local pain in all patients and numbness of the back in six patients after the procedure. Conclusions Combined RF neurotomy and steroid nerve block produced substantial improvement in terms of long-term pain relief and quality of life.

Chinchilla laniger has been reported as an experimental definitive host for Taenia solium; however no information about its suitability and yield of gravid tapeworm proglottids containing viable and infective eggs has been published. In total 55 outbred female chinchillas were infected with 4 cysticerci each; hosts were immunodeppressed with 6 or 8 mg of methyl-prednisolone acetate every 14 days starting the day of infection and their discomfort was followed. Kinetics of coproantigen ELISA or expelled proglottids was used to define the infection status. Efficiency of tapeworm establishment was 21% and of parasite gravidity was 8%; chinchillas showed some degree of suffering along the infection. Viability of eggs obtained from gravid proglottids was tested comparing methods previously published, our results showed 62% viability with propidium iodide, 54% with trypan blue, 34% with neutral red, 30% by oncosphere activation and 7% with bromide 3-(4,5-dimetil-tiazol-2-il)-2,5-difenil-tetrazolio (MTT) reduction; no statistical differences were obtained between most techniques, except activation. Four piglets were infected with 50,000 eggs each, necropsy was performed 3 months later and, after counting the number of cysticerci recovered, the percentage of infection was similar to data obtained with T. solium eggs recovered from humans. Our results demonstrate that the experimental model of T. solium taeniasis in C. laniger is a good alternative for providing eggs and adult tapeworms to be used in different types of experiments; optimization of the model probably depends on the use of inbred hosts and on the reduction of infected animals' suffering.

Methylprednisolone (MP) released by poly(d,l-lactide-co-glycolide) microspheres (PLGA MS) was monitored in plasma after intra-articular (i.a.) administration into rat joint. A validated LC-ESI-MS/MS method was used to quantify the plasmatic concentrations of MP. The calculated pharmacokinetic parameters were compared to those obtained after the i.a. administration of a commercially available suspension of MP acetate (MPA). Different pharmacokinetic profiles were observed in the two formulations, and a lower peak level (C(max) = 13.7 ± 4.3 ng · mL(-1)) and AUC(0-72 h) (198 ± 45 ng · mL(-1) · h) were observed for MP-PLGA MS than MPA (C(max) = 18.4 ± 2.7 ng · mL(-1)) and AUC(0-72 h) (943 ± 249 ng · mL(-1) · h). The administration of MP-PLGA MS resulted in a rapid increase in the MP concentration at 30 min, with a t(max) at 0.8 ± 0.3 h. Instead, for the MPA suspension the t(max) was 32.0 ± 13.9 h. These differences were indirectly confirmed by the evaluation of the extra-articular effects, namely, carrageenan-induced paw edema, since MP-PLGA MS showed a lower anti-inflammatory activity than MPA.

The effects of host age and immune suppression on abomasal parasitic infection in sheep were investigated following single experimental oral infections with MHco3 (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of Haemonchus contortus in naive 5-month-old crossbred lambs (n = 1 per group) and 15-month-old Greyface sheep treated with methyl prednisolone acetate (n = 2 per group) or without corticosteroid treatment (n = 2 per group). Adult female H. contortus in 5-month-old lambs (n = 1 per group) shed on average 6.5, 3.1 and 8.0 times more eggs than in 15-month-old sheep (n = 4 per group) following infection with MHco3 (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of H. contortus, respectively, over a period of 28 days following the commencement of patency. There was no obvious effect of age of sheep or corticosteroid treatment on the abomasal establishment of H. contortus or on in vitro assays for egg hatching or larval feeding at different concentrations of anthelmintics, although statistical analysis could not be performed due to the small group sizes.

Introduction/Background Tennis elbow is a prevalent musculoskeletal disorder. In recent years ozone injection has been proposed as a treatment for many musculoskeletal disorders. The aim of this study was to compare the effect of ozone with the standard treatment of steroid injection in patients with tennis elbow, resistant to conservative treatments. This comparison is made according to VAS score, pressure pain threshold (PPT) and modified Mayo clinic performance index for elbow. Material and method In this study 64 patients with tennis elbow, which have had the symptoms for more than 3 months and were resistant to conservative treatments, were randomized to two groups. In steroid injection group 40 mg of methylprednisolone acetate and in zone injection group 4 mL of ozone with concentration of 15 mcg/mL was injected. Thirty-two patients in steroid and 29 patients in ozone injection group finished this study. Data were gathered before injection and 2 and 6 months after that by VAS score, modified Mayo clinic performance index for elbow and PPT (measured by the means of an algometer). Variables were compared between the two groups and also the changes in each group have been measured in reference to baseline data. Results In both groups VAS score, Mayo clinic performance index and PPT improved significantly in 2 and 6 month follow-up. Steroid injection was significantly better than ozone injection in improving 2 and 6 months pressure pain threshold and 6 months Mayo clinic performance index. Other data did not show significant difference between the two groups. Conclusion Both steroid and ozone injection improved pain and function in patients with recalcitrant tennis elbow for at least 6 months. Steroid injection was superior to ozone injection in improving PPT in 2 and 6 month and Mayo clinic performance index score at 6 month follow-up.

Tadalafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Nitric oxide (NO) functions as a retrograde neurotransmitter in the spinal cord, and postsynaptic structures respond to NO by producing cGMP. The concentrations of cGMP in the spinal cord are controlled by the actions of PDE. The aim of the study was to evaluate and compare the effects of the use of both methylprednisolone and tadalafil on serum and tissue concentrations of NO, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tissue glutathione peroxidase (GSH-Px) activity in rats with spinal cord injury (SCI). SCI was induced in Wistar albino rats by dropping a 10 g rod from a 5.0 cm height at T8-10. The 28 rats were randomly divided into four equal groups: tadalafil, methylprednisolone, non-treatment and sham groups. Rats were neurologically tested at 24 hours after trauma. At the end of the experiment, blood samples were collected and spinal cord tissue samples were harvested for biochemical evaluation. The tissue level of NO was increased in the tadalafil group compared with the non-treatment and methylprednisolone groups (p0.05). The tissue levels of SOD and GSH-Px did not differ between the groups. Serum levels of NO were higher in the tadalafil group than in the non-treatment group (p0.05). The increase in serum SOD levels was greater in the tadalafil group than the methylprednisolone group. Serum MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group (p0.05). Tissue MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group and sham groups (p0.05). Although there was no difference in neurological outcome scores between the tadalafil, methylprednisolone and non-treatment groups (p0.05), the animals in the tadalafil and methylprednisolone groups tended to have better scores than the non-treatment group. Thus, tadalafil appears to be beneficial in reducing the effects of injury to the spinal cord by increasing tissue levels of NO and serum activity of SOD.

A rapid, sensitive and specific liquid chromatography-electrospray-tandem mass spectrometric (LC-ESI-MS/MS) method for the simultaneous detection and quantitation of methylprednisolone acetate (MPA) and methylprednisolone (MP) in rat plasma, using a triple-stage quadrupole, has been developed and validated. MP-D(2) was used as internal standard (IS) and acetonitrile was added to plasma samples for protein precipitation. After extraction with dichloromethane, the analytes were separated on a C-12 reversed-phase column by isocratic elution (6min at a flow rate 0.2mLmin(-1)) with water containing 0.01% formic acid (A) and acetonitrile (B) (50:50, v/v). Quantitation was performed in positive ion multiple reaction monitoring (MRM) mode by applying the following precursor-to-product ion transitions: MPA m/z 417-->135+161+253; MP m/z 375-->135+161+253; IS m/z 377-->135+161+253. The method, validated over the concentration range 6-600ngmL(-1), has been shown to meet the current requirements of bioananalytical validation, providing satisfactory results in terms of linearity, recovery, intra-day and inter-day precision and accuracy. The lower limit of quantitation (LLOQ) was 6ngmL(-1) for both the analytes (0.080 and 0.072pmol injected for MP and MPA, respectively). The method was successfully applied to monitor the plasma levels of MPA and MP following intra-articular (IA) injections of a low MPA (Depo-Medrol((R))) dose in rats.

15. Raibley SO, Beckett RP, Nowakowski A: Multiple traumaticbone cysts of the mandible. J Oral Surg 37:335, 197916. Magliocca KR, Edwards SP, Helman JI: Traumatic bone cyst ofthe condylar region: Report of 2 cases. J Oral Maxillofac Surg65:1247, 200717. Wright JG, Yandow S, Donaldson S, et al: A randomized clinicaltrial comparing intralesional bone marrow and steroid injec-tions for simple bone cysts. J Bone Joint Surg Am 90:722, 200818. Capanna R, Dal Monte A, Gitelis S, et al: The natural history ofunicameral bone cyst after steroid injection. Clin Orthop RelatRes 166:204, 198219. Scaglietti O, Marchetti PG, Bartolozzi P: Final results obtained inthe treatment of bone cysts with methylprednisolone acetate(depo-medrol) and a discussion of results achieved in other bonelesions. Clin Orthop Relat Res 165:33, 198220. Hansen LS, Scapone J, Sprout C: Traumatic bone cysts of jaws:Report of sixty-six cases. Oral Surg Oral Med Oral Pathol 37:899, 197421. Wilkins R: Unicameral bone cysts. J Am Acad Orthop Surg8:217, 200022. Oppenheim WL, Galleno H: Operative treatment versus steroidinjection in the management of unicameral bone cysts. J PedOrthop 4:1, 198423. Yu CL, D’Astous J, Finnegan M: Simple bone cysts. The effectsof methylprednisolone on synovial cells in culture. Clin OrthopRelat Res 34, 1991J Oral Maxillofac Surg68:212-217, 2010

Steroids are well recognized for their excellent anti-inflammatory actions. After first steroid was used to treat painful arthritis, it became apparent that epidural steroid administration may be effective for management of sciatica pain and low back pain. Later on, other types of neural blockade techniques, such as facet joint injections, were described as the treatment option for low back pain. The most commonly used steroid preparations for the neuraxial blockade are methylprednisolone acetate (Depo-Medrol, Pfizer, New York, NY), triamcinolone acetonide and diacetate (Kenalog, Bristol-Myers Squibb, Princeton, NJ), betamethasone acetate (Celestone, Schering-Plough Corporation, Kenilworth, NJ), and dexamethasone (Decadron, Merch & Company Inc, West Point, PA). Glucocorticoids are postulated to improve immunologic activity and wound healing. They are also required to maintain normal carbohydrate, lipid, and protein metabolism. The formulations available for injectable steroids contain various chemicals, which include buffers, polyethylene glycol, benzyl alcohol, and benzalkonium chloride. Toxicities that are associated with epidural steroid injections (ESIs) are often delayed. There have been several cases that reported injury to the central nervous system following transforaminal ESIs. The most accepted explanation for this is an occlusion of the segmental artery by the steroid particulate matter or embolization through the vertebral artery.

The influence of dietary protein supply on the nutritional penalty associated with the acquisition phase of the immune response to gastrointestinal nematodes in lambs was investigated. Groups of lambs were offered either a low-protein diet (L; 62 g metabolizable protein (MP)/kg dry matter (DM)) or high-protein diet (H; 95 g MP/kg DM) while being either infected with the equivalent of 2.000 L3 Trichostrongylus colubriformis/day (IF), similarly infected and concurrently immuno-suppressed with methylprednisolone acetate (ISIF), immuno-suppressed only (IS) or kept as uninfected controls (C). Body composition of all animals was measured on days −8 and 76 of infection using X-ray computed tomography. Temporal changes in serum phosphate and serum albumin concentrations, which provided an indicator of pathological damage, in addition to patterns of total daily nematode egg excretion and comparative worm burdens at slaughter indicated that a protective immune response was developed in H-IF, but not L-IF, H-ISIF or L-ISIF groups. Compared to their respective non-infected controls, the gross efficiency of use of metabolizable energy (ME) for net energy (NE) deposition in the carcass was reduced by 0.23 in H-IF (P < 0.05), 0.13 in H-ISIF (P > 0.05), 0.49 in L-IF (P < 0.01) and 0.23 in L-ISIF (P > 0.05). It is concluded that the reduction in ME utilization and reduced performance, which can be attributed to the immunological response, are lessened in animals offered a high-protein diet. Furthermore, evidence is presented to indicate a possible association between T. colubriformis L3 IgA antibody production and loss of performance in lambs infected with this nematode.

Meralgia paresthetica is an entrapment neuropathy involving the lateral femoral cutaneous nerve of the thigh. Patients complain of a persistent burning sensation, tingling and aching pain, and hypersensitivity or hyposensitivity in the anterolateral aspect of the thigh. Numerous direct and indirect causes for the disease have been suggested in the literature.We present 12 cases that were diagnosed to have meralgia paresthetica due to tight new fashion low cut trousers (‘taille basse’). The diagnosis was confirmed by injecting a small amount of a short acting local anesthetic around the lateral femoral cutaneous nerve which alleviated the symptoms for several hours. Electrophysiologic studies were sensitive in 83.3% of the cases.All cases were treated successfully using conservative methods, namely avoiding tight trousers, local steroid infiltration and weight reduction.

Purpose To evaluate the timing of improvement after extra-articular steroid injection, the incidence of a postinjection pain flare (a delayed postinjection transient increase in pain), and the role of the injection acidity in the postinjection flare. Methods One hundred twenty-five patients with trigger finger (88 patients) or de Quervain's tenosynovitis (37 patients) were prospectively randomized in this double-blind study to receive either an injection of steroid, lidocaine, and bupivacaine alone (standard injection, acidic pH) or an injection of steroid, lidocaine, bupivacaine, and bicarbonate (balanced injection, neutral pH). All patients completed a visual analog scale for pain before and immediately after the injection, daily for 7 days, and then again at 6 weeks. A flare reaction was defined as an increase in the visual analog scale score by 2 or more points any time after the injection. Results All patients immediately responded to the steroid injection, but pain rebounded to preinjection levels by day 1. In both groups the pain then gradually declined over the course of 7 days. In the balanced group, 23 of the 68 patients had flare reactions. In the standard group, 18 of the 57 patients had flare reactions. The difference between groups was not significant. Conclusions Patients respond to extra-articular steroid injections with gradual improvement over the course of the first week. An increase in pain, or flare reaction, in the days following a steroid injection was noted in 33% of patients. A pH-balanced injection did not significantly decrease the risk of a flare reaction. Type of study/level of evidence Therapeutic I.

The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone–tetracycline is one published method for immunosuppressing mice for the production of C. parvum oocysts. However, dexamethasone-induced immunosuppression is variable, because it is dependent on the total daily water consumption of each individual mouse. The changes in circulating leukocytes and other immune system associated organs before, during and after dexamethasone suppression were analyzed for comparison with a new single injection methylprednisolone acetate (MPA) suppression model. The dexamethasone-induced immunocompromised state was associated with a greater than 90% sustained drop in circulating T-lymphocytes, a greater than 700% increase in circulating mature segmented neutrophils and a severe depletion of circulating monocytes. The thymus and spleen decreased in size by over 80%. Oocyst shedding in suppressed mice started within 4 days of oocyst inoculation and persisted for 6 days post-dexamethasone treatment. Seven days after dexamethasone withdrawal, circulating neutrophils still were 549% higher than controls. Circulating CD3 and CD4 lymphocytes remained depressed by 85–90% while on dexamethasone and for 7 days after discontinuing dexamethasone. CD8 lymphocyte numbers initially decreased by 90%, but rose even while on dexamethasone and even with severe thymic involution. At day 7 post-dexamethasone treatment, the spleen was 119 mm3, approximating the same size as controls. Fourteen days post-dexamethasone treatment, which was 8 days after oocyst shedding had ceased, the CD8 counts per 5000 events were only 1.6% below controls, while the CD3 and CD4 counts were still depressed by 66%. The thymus now was about one quarter smaller than the controls. The rise in circulating CD8 lymphocytes, when oocyst production stopped, suggests that CD8 positive lymphocytes may play a significant role in vivo in clearing the parasite. The overall pattern of immunosuppression was nearly identical to that observed with the methylprednisolone acetate immunosuppression model.

Seven steroid derivatives (hydrocortisone, hydrocortisone acetate, prednisolone, prednisolone acetate, methylprednisolone acetate, dexamethasone and fludrocortisone acetate) irradiated in the solid phase 10 MeV electrons, were studied by chromatographic methods (TLC and HPLC). Before the irradiation the derivatives contained different amounts of the following impurities: cortisone, cortisone acetate, prednisolone, prednisolone acetate and prednisone. After irradiation with a dose of upto 200 kGy radiolytic products were identified: cortisone, cortisone acetate, prednisone, prednisolone and methylprednisone acetate. All the identified radiolytic products were formed as a result of oxidation of the substituent at C 11 , and in some cases the oxidation was accompanied by cleavage of the ester bond. The content of impurities before irradiation did not exceed 0.8%, while after the irradiation the content of the products of radiolysis depended on the kind of the derivative and the dose, and varied from 0.6% for a dose of 25 kGy to 4.03% for a dose of 200 kGy. For some derivatives, a linear relationship was found between the loss of a given steroid content and the dose. The studied steroid derivatives are characterised by high radiochemical stability and their sterilisation by irradiation does not lead to loss of the active substance below 97%, i.e. the lower limit admissible by the pharmacopoeias.

Objective To describe the safety and potential therapeutic benefit of spinal manipulation postepidural injection in the nonsurgical treatment of patients with cervical and lumbar radiculopathy. Methods The study design was a retrospective review of outcomes of 20 cervical and 60 lumbar radiculopathy patients who underwent spinal manipulation postepidural injection in a hospital setting. Patients received either fluoroscopically guided or computed tomography (CT)–guided epidural injection of a combination of lidocaine and Depo-Medrol. The manual therapy consisted of an immediate postepidural application of flexion distraction mobilization and then high-velocity, low-amplitude spinal manipulation to the affected spinal regions. Outcome criteria were empirically defined as significant improvement, temporary improvement, or no change. The minimum follow-up time for all patients was 1 year. Results There were no complications associated with spinal manipulation, whereas 3 complications associated with the epidural injection procedure were noted. Of lumbar spine patients, 36.67% (n = 22) noted significant improvement, 41.67% (n = 25) experienced temporary improvement, and 21.67% (n = 13) reported no change. Of the patients undergoing spinal manipulation after cervical epidural injection, 50% (n = 10) noted significant improvement, 30% (n = 6) experienced temporary improvement, whereas 20% (n = 4) exhibited no change. Conclusions These data suggest that spinal manipulation postepidural injection is a safe nonsurgical procedure to use in the treatment of the patient with radiculopathy of spinal origin. This is also the first report of the use of spinal manipulation postepidural injection in the cervical spine.

Stretanski MF. H-reflex latency and nerve root tension sign correlation in fluoroscopically guided, contrast-confirmed, translaminar lumbar epidural steroid-bupivacaine injections. Arch Phys Med Rehabil 2004;85:1479-82. Objectives To examine the correlation between physical examination parameters, commonly referred to as "nerve root tension signs," and H-reflex latency measurements both pre- and postepidural steroid-bupivacaine (Marcaine) injection, and to propose mechanisms of pain alleviation. Design Prospective observational, with H-reflex latency measurement and physical examination at baseline and at 10 minutes postinjection. Setting Physical medicine and rehabilitation practice, outpatient surgical center, and community setting. Participants Ten consecutively recruited patients (6 women, 4 men; age range, 40–71y) with clinical radiculopathy and compatible magnetic resonance imaging findings, who were unaware of the outcome measures. Interventions Patients received a fluoroscopically guided, contrast-confirmed, paramedian translaminar lumbar epidural injection of 120mg of methylprednisolone acetate (80mg/mL) and 2.0mL of .25% preservative-free Marcaine. Main outcome measures Seated slump testing (SST), straight-leg raising (SLR), and H-reflex latency were measured bilaterally both pre- and postinjection. Differences were measured by using the paired t test in an A-B design. Results All SST of the affected (injected) side improved from pre- to postinjection, with 3 patients reporting discordant hamstring pain and 7 reporting no pain. SLR ability increased by an average of 29°±12°, corresponding to an average relative increase of 54% on the affected side. A statistically significant difference was found (Student t test, P =.02) between pre and post H-reflex latency on the affected side but not when comparing changes between affected and unaffected sides (Student t test, P =0.6). Conclusions Significant improvements in SST and SLR result from low volume epidural injection of Marcaine, with questionable prolongation of the H-reflex to the gastrocnemius-soleus complex on the affected side.

Purpose There have been few prospective studies evaluating the results of nonsurgical treatment of a well-defined patient cohort with symptomatic basal joint osteoarthritis of the thumb. This prospective study uses a validated outcome instrument to examine the effectiveness of a single steroid injection and 3 weeks of splinting in patients with osteoarthritis in Eaton stages 1 to 4 with a minimum of 18 months of follow-up evaluation. Methods Thirty consecutive patients (30 thumbs) were studied prospectively to evaluate the efficacy of a single injection of corticosteroid into the trapeziometacarpal joint, followed by immobilization in a thumb spica splint for 3 weeks. All patients answered an outcome-based questionnaire (Disabilities of the Arm, Shoulder, and Hand) and were examined before injection, 6 weeks after injection, and at final follow-up examination (minimum, 18 months). Eaton radiographic stage was recorded by 3 independent observers. Results At 6 weeks 13 patients had improvement in pain intensity and 17 patients reported no symptomatic improvement. Twelve of those with relief at 6 weeks continued to have relief at long term follow-up evaluation (mean, 25 months). Of patients with long-term relief average grip strength of the affected thumb was 95% of contralateral side, whereas those without relief had grip strength values that were 60% of contralateral side. For those patients without relief at 6 weeks there was no improvement seen at later follow-up evaluation. Five patients with Eaton stage 1 disease had an average of 23 months of relief with nonsurgical treatment. In stage 2 and stage 3 disease 7 thumbs improved at 6 weeks after injection and 6 thumbs had long-term relief. In stage 4 disease, 6 thumbs had neither short-term nor long-term relief with the injection. Disease side, handedness, and smoking did not affect outcomes. At final follow-up evaluation 12 thumbs had had surgical treatment. Conclusions Steroid injection with splinting for the treatment of basal joint arthritis of the thumb provided reliable long-term relief in thumbs with Eaton stage 1 disease but provided long-term relief in only 7 of 17 thumbs with Eaton stage 2 and stage 3 basal joint arthritis.

A 61-year-old patient with severe stump pain required hospitalization and intravenous opioids for pain control. After evaluation by our anesthesia pain management service, we concluded that the patient had a neuroma at the site of sciatic nerve transection and that injection of a mixture of local anesthetic and corticosteroid at the site of the neuroma was the most appropriate management. Because the alternative methods of nerve localization (eg, motor stimulation, paresthesia) were unlikely to be successful, we felt that the most reliable way to accomplish this task was to use live ultrasound guidance. After a series of 4 ultrasound-guided blocks with bupivacaine and methylprednisolone acetate, the patient's pain was alleviated to the point at which it was managed with occasional doses of oral opioids.

Five female specific pathogen-free (SPF) cats inoculated intradermally with B. henselae and bacteremic for 4 weeks, and one cat inoculated with 0.9% NaCl, were bred with uninfected SPF male cats. The uninfected female became pregnant with one breeding, while three infected cats became pregnant 1-12 weeks later, after repeated breedings. Two infected females either did not become pregnant or maintain pregnancies despite repeated breedings. Infected cats produced anti-B. henselae IgM and IgG antibodies. Fetuses and kittens of infected cats were not infected and did not produce anti-B. henselae antibodies. Male cats bred with infected females did not become infected or seroconvert. Maternal anti-B. henselae IgG antibodies detected in sera of kittens 2 weeks post-partum were no longer detectable 10 weeks post-partum. These findings suggest that B. henselae causes reproductive failure in female cats, but is not transmitted transplacentally, in colostrum or milk, or venereally. Infected cats immunosuppressed with methylprednisolone acetate after their kittens were weaned had no detectable bacteria in tissues, suggesting that they were no longer infected.

Summary Objective: A study was conducted to define the relationship between oriental channel imbalance and pain of the equine hindlimb. Methods: One hundred eighty-five lame and muscle sore horses from a general equine practice in Virginia were examined by a single observer using traditional manual palpation of the acupuncture channels. The six hindlimb channels were evaluated and graded with particular emphasis on the reactivity of three transpositional acupoints, BL 18, BL 19, BL 20, and five traditional veterinary acupoints Yao Zhong, Shen Shu, Xie Qi, Feng Men, and Fu Tu. All lame patients were evaluated with western methods to establish an anatomical diagnosis. All nonlame horses with channel imbalance were treated with either an intra-articular anesthetic, an intra-articular cortisone, methylprednisolone acetate, or a hyaluronate and triamcinalone combination. The medications were injected into either the three compartments of the stifle joint, tarso-metatarsal and distal inter-tarsal joints, metatarsophalangeal joint, or the distal interphalangeal joint The joint injections were conducted in sequence, distal to proximal, until a definitive change in channel imbalance had occurred. Chi Square analysis was used to assess different frequencies of channel imbalance and the sites responsible for that imbalance, with P Results: Channel imbalance was only indirectly associated with extra-articular pathology. Intra-articular structures of three joints of the distal hindlimb, the distal tarsus, metatarsophalangeal, and distal interphalangeal, accounted for all the observed abnormal, referred diagnostic acupoints. In the examined population, channel imbalance was significantly more frequently related to the distal tarsus than the hind fetlock, and both of these were significantly more frequently involved than the distal interphalangeal joint. Channel imbalance relating to the dorsal aspect of the digit was significantly more frequent in metatarsophalangeal lameness than in distal tarsal lameness. Neither the stifle nor midback pain was directly associated with projected, as opposed to local, channel imbalance. If projected channel imbalance could be defined as the presence of reactive acupoints not in the immediate vicinity of the local site of pain, then the projected acupoints detected in stifle lameness or back pain were associated with the tarsus or the hind fetlock. Conclusions: The sites of hindlimb pathology resulting in channel imbalance were intra-articular, and they were located within the distal tarsal, the metatarsophalangeal and the distal interphalangeal joints. Channel diagnosis reflected intra-articular inflammation of only these three joints, and further diagnostic procedures were required to establish a definitive western diagnosis. The presence of channel imbalance should be used to determine pattern differentiation in Traditional Chinese Medicine.

Objective: Pig hearts transplanted into unmedicated newborn baboons do not undergo hyperacute rejection by preformed xenoantibody and complement. These grafts are rejected at days 3 to 4 in association with the infiltration of macrophages and natural killer cells. We investigated whether an immunosuppressive regimen used widely in cardiac allotransplantation could reduce this cellular response and prolong xenograft life. Methods: Ten newborn baboons underwent heterotopic pig cardiac xenotransplantation. Five baboons were immunosuppressed with mycophenolate mofetil (100 mg/kg), methylprednisolone acetate (0.8 mg/kg), and cyclosporine A (INN: ciclosporin; 10 mg/kg). Xenograft rejection was studied by light microscopy and immunofluorescence. The induced humoral response to porcine xenoantigens was documented by enzyme-linked immunosorbent assay using synthetic α-1,3-galactosyl epitopes coupled to bovine serum albumin. Results: Graft life was extended from a mean of 3.6 ± 0.5 days ( n = 5) to a mean of 6.2 ± 1.1 days ( n = 5, p = 0.01). In comparison with controls, explanted grafts from medicated baboons demonstrated reduced infiltration with natural killer cells and macrophages, but increased evidence of complement-mediated rejection substantiated by increased deposition of immunoglobulin M, complement, and fibrin. In all baboons receiving transplants, levels of both immunoglobulin M and immunoglobulin G anti-galactose were significantly increased after transplantation, with immunoglobulin G levels remaining persistently elevated. Conclusions: These results indicate that cyclosporine-based triple immunosuppression marginally prolonged xenograft survival and appears to have reduced the natural killer cell and macrophage infiltrates. The immunosuppressive protocol, however, was not adequate to prevent the induced immunoglobulin M humoral response and prevent complement-mediated graft injury. (J Thorac Cardiovasc Surg 1998;115:998-1006)

In recent years, new percutaneous techniques have been developed in interventional radiology. These methods are less aggressive, cost-saving, and require shorter hospital stays than classical surgical methods. The recent concept of percutaneously implantable biomaterials and drugs for bone treatment holds potential for the development of novel percutaneous radioguided procedures providing expanded therapeutic capabilities. 17 An intraosseous cyst is defined as a bony closed cavity containing fluid. It must be differentiated from ganglion cysts and subchondral cysts often observed in various arthropathies. Unicameral bone cysts (UBCs) (also called essential bone cysts or simple bone cysts ) and aneurysmal bone cysts (ABCs) are benign osteolytic lesions that weaken the bone and require surgical treatment to prevent pathologic fractures. The surgical approach to UBCs or ABCs may need to be aggressive because of their location or their extent. Their size or location may preclude excision, and recurrence of the cysts is frequent after surgery. The fluid nature of the contents of ABCs and UBCs permits intracavitary surgical or percutaneous injection.

Objective: To determine how acute synovitis, with and without intra-articular methylprednisolone acetate (MPA), affect synthesis of proteoglycan, total protein, and collagen in articular cartilage and total protein synthesis in synovial membrane. Design: Synovitis was induced in 10 ponies by the injection of 0.5 ng lipopolysaccharide (LPS) into the left radiocarpal and midcarpal joints every 2 days for a total of four treatments. Synovitis was documented by clinical examination and synovial fluid analyses. Two days before euthanasia, MPA (0.1 mg/kg) was injected with the last dose of LPS into both the left and right radiocarpal and midcarpal joints of five of these ponies. Proteoglycan synthesis in articular cartilage explants from these joints was measured by incorporation of sodium [ 35 S]sulfate. The size of the proteoglycan monomers and their aggregation with hyaluronan was assessed by size-exclusion chromatography. Protein synthesis in articular cartilage was measured by incorporation of [ 3 H]proline and collagen synthesis by conversion of [ 3 H]proline into [ 3 H]hydroxyproline. Protein synthesis was measured in synovial membrane explants by incorporation of [ 35 S]methionine. Results: Ponies developed carpal effusion and mild lameness accompanied by increased total nucleated cell count and total solids in synovial fluid in response to the LPS injections. Moderate to severe synovial membrane proliferation and inflammation were observed histopathologically in joints injected with LPS but no consistent light-microscopical changes were observed in the articular cartilage from these joints. Intra-articular MPA alone was associated with decreased proteoglycan synthesis and increased protein and collagen synthesis in the cartilage explants. Total protein synthesis by synovial membrane was also increased by MPA alone. In contrast, no differences in protein or proteoglycan synthesis were observed in explants from the joints with synovitis, with or without intra-articular MPA. Treatment with MPA, LPS, and LPS/MPA did not alter proteoglycan aggregate size, but LPS-induced synovitis resulted in an increase in the second largest population of monomers. MPA increased the synthesis of small proteoglycan monomers. Conclusion: Based on the methods used, acute synovitis prevented changes induced by intra-articular MPA alone. Results suggested that the effect of intra-articular MPA on joint metabolism was different between inflamed and normal joints. Experimental studies must consider the effect of inflammation, as well as the potential to introduce in vitro culture artifacts when investigating the effect of intra-articular corticosteroids on chondrocyte function.

Purpose To determine how corticosteroid injections for trigger finger affect the blood glucose level in diabetic patients and the clinical results of those injections. Methods Eighteen diabetic patients receiving a methylprednisolone injection for a single trigger finger were studied. Six patients had type I (juvenile-onset) diabetes and 12 patients had type II (adult-onset) diabetes. Patients recorded their usual blood glucose measurements and then they recorded their blood glucose measurements for 5 days after injection. Clinical efficacy of the injections was measured by avoidance of surgery. Results There were 3 men and 15 women with an average age of 58 years. The blood glucose level increased after corticosteroid injection for all patients. The first morning after injection showed the biggest increase in blood glucose level: 73% more than the average preinjection levels. By the fifth morning after injection the blood glucose levels still were increased by 26% more than the preinjection levels. This trend was marked particularly in type I diabetic patients, who had an average blood glucose level increase the first morning after injection of 145%, which decreased over 5 days to 22% greater than baseline levels. Sixteen patients had follow-up evaluation over a period of 1 year and of these 16 patients 7 required surgery for this condition. Conclusions A digital injection of the corticosteroid methylprednisolone acetate in diabetic patients with trigger finger causes a hyperglycemic effect that lasts for at least 5 days but can help prevent the need for surgery more than half the time. Type of study/level of evidence Therapeutic, Level IV.

Compounding pharmacies mix, combine, or alter drugs that are not otherwise available in the commercial market. This paper discusses the development of the compounding industry, and the various state and federal oversight authorities surrounding it. These entities are a necessary part of the healthcare delivery system, especially in hospitals and clinics where compounded drugs are needed in greater volume and cannot be produced on-site. Recently, however, the compounding industry has grown rapidly, and the industry controls that preserve safety and quality controls are no longer sufficient. In order for the industry to remain a viable option for safe medication to healthcare providers, changes need to be made to ensure the quality of the products. This objective could be made from within the industry through management or technology; however, this paper discusses how federal and state regulatory agencies can better ensure that no matter what the source, the public is supplied only with safe medication. As discussed later, it became apparent that regulatory responsibility over this industry between state and federal agencies was not clear. A thorough investigation by Congress has determined that lack of definition and clarification of Federal oversight created confusion and agency liability exposure in the compounding manufacturer industry. The most recent and extreme case occurred in late 2012, when an outbreak of fungal meningitis was caused by contaminated vials of methylprednisolone acetate, produced by the New England Compounding Center in Framingham, Massachusetts. The contaminated solution was injected into patient’ joints and spine to treat pain, but instead caused 751 infections and 64 deaths. In light of this horrific tragedy, the state and federal agencies, along with Congress, have investigated and discussed how to prevent this from happening again. The result of this investigation was the exposure of a gap in regulatory authority between the state boards of pharmacy that license pharmacies within their state, and the FDA which oversees the mass production and distribution of drugs nationally. This gap allowed facilities to operate under a state license, and hide behind state authority, even when there was evidence that they were operating more like a manufacturer. To close this gap, ensure compliance with safety controls, and prevent another outbreak of adverse events, Congress has enacted legislation, the Drug Quality and Security Act, to clarify jurisdictional definition, and require specific registration and reporting from compounding manufacturers. This paper discusses the strengths and weaknesses of the Drug Quality and Security Act, and what issues remain.