Miconazole and terbinafine induced reactive oxygen species accumulation and topical toxicity in human keratinocytes.

There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds.

The role of reactive oxygen species in the biological activity of antimicrobial agents: An updated mini review.

Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally. One of the major issues is that resistant pathogens decrease the efficacy of conventional antimicrobials. Accordingly, development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance. A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species (ROS). ROS are defined as a number of highly reactive molecules that comprise molecular oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). ROS exhibit antimicrobial actions against a broad range of pathogens through the induction of oxidative stress, which is an imbalance between ROS and the ability of the antioxidant defence system to detoxify ROS. ROS-dependent oxidative stress can damage cellular macromolecules, including DNA, lipids and proteins. This article reviews the antimicrobial action of ROS, challenges to ROS hypothesis, work to solidify ROS-mediated antimicrobial lethality hypothesis, recent developments in antimicrobial agents using ROS as an antimicrobial strategy, safety concerns related to ROS, and future directions in ROS research.

Multi-disciplinary Orthopaedics Rehabilitation Empowerment (MORE) program: A new standard of care for injured workers in Hong Kong.

BACKGROUND: The objective of this study is to evaluate the effects of the Multi-disciplinary Orthopaedics Rehabilitation Empowerment (MORE) Program on reducing chronic disability among injured workers and improving efficiency of work rehabilitation process. METHODS: A cohort of patients with workplace injuries in the lower back were recruited from orthopaedics clinics and assigned to either MORE group (n= 139) or control group (n= 106). Patients in MORE group received an early MRI screening and a coordinated multi-disciplinary management, while patients in the control group received conventional care. Outcome variables are time to return-to-work (RTW) from date of injury, waiting time for MRI screening and time to medical assessment board (MAB). RESULTS: Patients in the MORE Program had significantly shorter duration for RTW (MORE: 6.1 months, CONTROL: 12.8 months, p< 0.01), and more RTW cases (n= 64, 46.0%) compared to CONTROL group (n= 29, 27.4%). The MORE group also had much shorter waiting time for MRI scans (91.85 vs. 309.2 days, p< 0.001) and MAB referral after MRI scans (97.2 vs. 178.9 days, p= 0.001) compared to CONTROL group. CONCLUSIONS: The MORE Program which emphasizes early intervention and early MRI screening, is shown to be effective in shortening sick leave and improving RTW outcomes of injured workers.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

UNLABELLED: In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. INTRODUCTION: This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. METHODS: In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. RESULTS: The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. CONCLUSIONS: Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Limb Idleness Index (LII): a novel measurement of pain in a rat model of osteoarthritis.

OBJECTIVES: Mechanical allodynia during ambulation in osteoarthritis (OA) animal models can be assessed as decreased extent of loading or decreased duration of loading. We propose to measure gait adaptation to pain by both mechanisms with the development of Limb Idleness Index (LII) in a rat model of knee OA. METHODS: Rats were assigned to anterior cruciate ligament transection (ACLT), Sham, or Normal group (n = 6). Gait data were collected at pre-injury, 1, 2, 3 and 6 months post-injury. Ratios of target print intensity, anchor print intensity, and swing duration were combined to obtain LII. The association of gait changes with pain was assessed by buprenorphine treatment at 3 and 6 months post-injury. At 6 months, OA-related structural changes in knee joints were examined by µCT and results from histological scoring were correlated with LII. RESULTS: As compared to pre-injury level (range 0.75-1.20), LII in ACLT group was increased at 6 months post-injury, which was significantly higher than that in Sham and Normal groups (P = 0.024). The increase in LII in ACLT group was effectively reversed by buprenorphine treatment (P = 0.004). ACLT group exhibited a significantly higher maximum Osteoarthritis Research Society International (OARSI) score as compared to Sham (P = 0.005) and Normal (P = 0.006) groups. Significant correlation was found between LII and side-to-side difference in OARSI score (r = 0.893, P < 0.001). CONCLUSIONS: LII presents a good measurement for OA-related knee pain in rat model.

Reconstruction of hypoplastic thumb using hemi-longitudinal metatarsal transfer.

The treatment of hypoplastic thumb (modified Blauth's type IIIb and IV) by pollicization is culturally unfavourable in the Chinese population and digit preservation is preferred. An innovative reconstruction method using a nonvascularized hemi-longitudinal metatarsal graft was performed in six cases with an average follow-up of 87.7 months. Overall hand function was good, as assessed using the Jebsen hand function test. Grip strength and pinch power were significantly weaker than the normal contralateral hand. There was no neurovascular or wound complication. The only donor site complication was a metatarsal fracture, which healed uneventfully with casting. There had been no permanent morbidity to the donor site, as all donor metatarsals hypertrophied and regained normal growth potentials. Linear growth of the transferred metatarsals was evident radiologically (average 1.5 mm/year). Free hemi-longitudinal metatarsal transfer is a feasible method with good functional outcome in the attainment of a 5-digit hand in patients with type IIIb/IV hypoplastic thumb.

Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model.

UNLABELLED: This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification. INTRODUCTION: This study was conducted to examine the role of ER beta during fracture healing. METHODS: Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post-fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing. RESULTS: Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post-fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4. CONCLUSIONS: The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture.

Impaired bone healing in rabbits with steroid-induced osteonecrosis.

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.

Tendon adhesion measured by a video-assisted gliding test in a chicken model.

We developed a video-assisted gliding test to evaluate the gliding force and the flexion angle with unrestricted joint motion. Tendon adhesion was induced in a chicken model of flexor digitorum profundus (FDP) injury at the annular pulley region of the long toe. The chicken feet were harvested immediately after injury, and 2 weeks and 6 weeks after injury. During the gliding test, the injured FDP was pulled for 15 mm then returned to its initial position. The test was recorded using a video camera and registered to the gliding test mechanical data. The maximum flexion angle and gliding resistance were calculated. The maximum flexion angle was significantly decreased from 78 (SD 10) in controls to 42 (SD 22) in tendons with injury, while gliding resistance was significantly increased in week 2 (0.06, SD 0.05) and week 6 (0.07, SD 0.01) after injury.

Digital gangrene following a green pit viper bite.

In Hong Kong, the white-lipped green pit viper (Trimeresurus albolabris) accounts for the majority of venomous snake bites. In these patients, the cardinal features are local pain and swelling and mild coagulation abnormalities, but digital gangrene is uncommon. A 58-year-old woman was bitten on the left middle finger pulp by a white-lipped green pit viper. She developed local pain and swelling and coagulopathy, complicated by pulp tissue necrosis and digital gangrene of left middle finger. She fully recovered after amputation of the left middle finger at the mid portion.

Intraosseous glomus tumor treated by toe-to-finger transfer: case report.

We report a case of intraosseous glomus tumor that developed in the right ring finger distal phalanx of a 19-year-old man. Clinical and radiographic findings were atypical. The tumor was excised en bloc because of the extensive involvement. The left second toe was transferred to the right ring finger to reconstruct the excised finger part. Symptom relief, function, and cosmetic outcome were satisfactory during 2-year follow-up.

Incorporating ultrasound-measured musculotendon parameters to subject-specific EMG-driven model to simulate voluntary elbow flexion for persons after stroke.

BACKGROUND: This study was to extend previous neuromusculoskeletal modeling efforts through combining the in vivo ultrasound-measured musculotendon parameters on persons after stroke. METHOD: A subject-specific neuromusculoskeletal model of the elbow was developed to predict the individual muscle force during dynamic movement and then validated by joint trajectory. The model combined a geometrical model and a Hill-type musculotendon model, and used subject-specific musculotendon parameters as inputs. EMG signals and joint angle were recorded from healthy control subjects (n=4) and persons after stroke (n=4) during voluntary elbow flexion in a vertical plane. Ultrasonography was employed to measure the muscle optimal length and pennation angle of each prime elbow flexor (biceps brachii, brachialis, brachioradialis) and extensor (three heads of triceps brachii). Maximum isometric muscle stresses of the flexor and extensor muscle group were calibrated by minimizing the root mean square difference between the predicted and measured maximum isometric torque-angle curves. These parameters were then inputted into the neuromusculoskeletal model to predict the individual muscle force using the input of EMG signals directly without any trajectory fitting procedure involved. FINDINGS: The results showed that the prediction of voluntary flexion in the hemiparetic group using subject-specific parameters data was better than that using cadaveric data extracted from the literature. INTERPRETATION: The results demonstrated the feasibility of using EMG-driven neuromusculoskeletal modeling with direct ultrasound measurement for the prediction of voluntary elbow movement for both subjects without impairment and persons after stroke.

An analysis of causes and treatment outcome of chronic wrist pain after distal radial fractures.

Healed distal radial fractures are frequently complicated by chronic wrist pain which is multifactorial and can be debilitating. An accurate delineation of the pathoanatomy is the key for successful treatment. This study reviewed 22 patients who had surgical treatment between 1997 and 2001 for chronic wrist pain after distal radial fracture. Four patterns of pathoanatomy were identified: (1) ulnar impaction caused by radial malunion and shortening; (2) ulnar styloid non-union; (3) triangular fibrocartilage complex (TFCC) tears with or without distal radioulnar joint (DRUJ) instability; and (4) intercarpal ligament injuries and chondral lesions. Surgical treatment directed towards identified abnormalities gave satisfactory outcome. At six months after surgery the mean functional score improved 36%, mean pain score decreased 50%, mean grip strength improved 25%, and 64% of patients returned to work.

Needle aponeurotomy for Dupuytren's contracture.

PURPOSE: To review the efficacy and safety of needle aponeurotomy for Dupuytren's contracture in Chinese patients. METHODS: Seven men and one woman aged 50 to 80 (mean, 67) years underwent needle aponeurotomy for Dupuytren's contracture. Five were manual workers and the other 3 were retired. Their chief complaints were difficulty moving the fingers, clumsiness of the hand, and occasional pain in the palm. No patient had any family history of Dupuytren's contracture. RESULTS: 41 points were released in 13 fingers (3 middle, 3 ring, and 7 little). Immediately after release, the respective mean flexion contracture correction of the metacarpophalangeal and proximal interphalangeal joints were 50 (from 50 to 0) and 35 (from 46 to 11) degrees. At 22-month follow-up, the respective mean residual flexion contracture of both joints were 12 and 27 degrees; the corresponding long-term improvements were 70 and 41%. No patient had a wound complication or neurovascular injury. All had a normal score for Disabilities of the Arm, Shoulder, and Hand. CONCLUSION: For Chinese patients with Dupuytren's contracture, needle aponeurotomy is safe and effective. Long-term correction is better maintained in metacarpophalangeal than proximal interphalangeal joints (70 vs 41%).

Firing properties of motor units during fatigue in subjects after stroke.

The purpose of this work was to investigate the electromyographic (EMG) fatigue representations in muscles of subjects after stroke at the level of motor unit, based on the analysis of mean power frequency (MPF) in the power density spectrum (PDS) for intramuscular EMG and our previous modeling and experiment studies on the neuromuscular transmission failure (NTF). NTF due to the local muscular fatigue had been captured in motor unit signals from healthy subjects during a submaximal fatigue contraction previously. In this study, the EMG signals for the biceps brachii muscles were collected by needle electrodes from the affected and unaffected arms of six hemiplegic subjects after stroke, and from the dominated arm of six healthy subjects during a full maximum voluntary contraction (MVC) and a subsequent 20% MVC. The MPF of EMG trials detected intramuscularly during the full and 20% MVCs, and the parameters of motor unit action potential trains (MUAPTs) during 20% MVC were analyzed in three groups: the normal (from healthy subjects), unaffected (from subjects after stroke), and affected (from subjects after stroke). It was found that during the full MVC the MPFs of the normal and unaffected groups decreased more than the affected when monitored by a moving time window of 2 s. The comparison on the overall MPF during the full MVC for these three groups over the whole time course of the EMG signal (18 s) were: the affected overall MPF was higher than the unaffected (P < 0.05); and the unaffected overall MPF was larger than the normal (P < 0.05). However, no significant decrease in MPF was found for these three groups during 20% MVC. The NTF was captured in most MUAPTs in the groups of the normal and unaffected rather than in the affected group, symbolized by the lowered rates of change (RCs) of firing rate (FR) (P < 0.05), more MUAPTs with positive RCs of maximum oscillation (MO) in MUAPT power density spectra (P < 0.05), and the significant higher RCs of minimum inter-pulse interval (MINI) (P < 0.05) in the normal and unaffected compared to the affected group. Enhanced neural drives to the motor units of the unaffected and affected groups were observed during 20% MVC, which possibly came from the bilateral neural inputs due to the disinhibition of the ipsilateral projections in subjects after stroke. For identifying the fatigue associated with NTF, the motor unit firing parameters, FR, MINI, and MO, were more sensitive than the MPF. The results obtained in this work provided a further understanding on the EMG of the fatigue processes in paretic and non-paretic muscles during voluntary contractions.

[Arthroscopic Volar Wrist Ganglionectomy.] / Résection des kystes synoviaux palmaires par arthroscopie.

As an original technique developed by our department, the preliminary result of arthroscopic resection of volar wrist ganglion was first published in 2003. Since then, there were few reports in the literature concerning this new treatment method. The aim of the study is to evaluate the long-term outcome of this treatment technique. From August 1997 to April 2005, 21 volar wrist ganglia with average size of 2 cm (range 1-4 cm) were treated. The average age of patients was 48.6 (range 18-63). Thirteen ganglia had previous treatment including either aspiration or open excision. Seventy-one percent of the operations were performed under local anesthesia. Wrist arthrogram was performed in 9 cases. Seven cases showed origin from radiocarpal joint and all proceeded to arthroscopic resection successfully. Arthroscopically, 75% of ganglia arose from the interval between radioscaphocapitate and long radiolunate ligament, and 25% from the interval between long radiolunate and short radiolunate ligament. Sixteen of the 21 ganglia could be excised by arthroscopic technique. The average follow up was 56 months (range 101 - 9 months). There were 2 recurrences. One was treated with repeated arthroscopic excision and the other by open excision. There was no impairment of wrist motion and function in all patients. No neurovascular complication was encountered. Arthroscopic resection was an effective treatment method for well-selected volar wrist ganglion arising from the radiocarpal joint in long run.

[Arthroscopic volar wrist ganglionectomy]. / Résection des kystes synoviaux palmaires par arthroscopie.

As an original technique developed by our department, the preliminary result of arthroscopic resection of volar wrist ganglion was first published in 2003. Since then, there were few reports in the literature concerning this new treatment method. The aim of the study is to evaluate the long-term outcome of this treatment technique. From August 1997 to April 2005, 21 volar wrist ganglia with average size of 2 cm (range 1-4 cm) were treated. The average age of patients was 48.6 (range 18-63). Thirteen ganglia had previous treatment including either aspiration or open excision. Seventy-one percent of the operations were performed under local anesthesia. Wrist arthrogram was performed in 9 cases. Seven cases showed origin from radiocarpal joint and all proceeded to arthroscopic resection successfully. Arthroscopically, 75% of ganglia arose from the interval between radioscaphocapitate and long radiolunate ligament, and 25% from the interval between long radiolunate and short radiolunate ligament. Sixteen of the 21 ganglia could be excised by arthroscopic technique. The average follow up was 56 months (range 9-101 months). There were 2 recurrences. One was treated with repeated arthroscopic excision and the other by open excision. There was no impairment of wrist motion and function in all patients. No neurovascular complication was encountered. Arthroscopic resection was an effective treatment method for well-selected volar wrist ganglion arising from the radiocarpal joint in long run.

Active mobilisation after flexor tendon repair: comparison of results following injuries in zone 2 and other zones.

PURPOSE: To prospectively study the role of active mobilisation after flexor tendon repair. METHODS: The standard modified Kessler's technique was used to repair 46 digits in 32 patients with flexor tendon injuries. Early active mobilisation of the repaired digit was commenced on the third postoperative day. Range of movement was monitored and recovery from injury in zone 2 was compared with injury in other zones. RESULTS: There were 24 and 22 injuries in zone 2 and other zones respectively. The total active motion score of the American Society for Surgery of the Hand was measured. Patients with zone-2 injuries achieved similar results to those with other-zone injuries apart from a 3-week delay in recovery. The final results were good to excellent in 71% and 77% of zone-2 and other-zone cases respectively (p < 0.05). There were 2 ruptures in zone-2 and one rupture in zone-3 repairs (6.5%). CONCLUSION: Preliminary results of this study showed that active mobilisation following flexor tendon repair provides comparable clinical results and is as safe as conventional mobilisation programmes although recovery in patients with zone-2 injury was delayed.

Is symptomatology useful in distinguishing between carpal tunnel syndrome and cervical spondylosis?

Hand paraesthesia is a common symptom found in patients either with carpal tunnel syndrome or cervical spondylosis. To differentiate between the two conditions, it is important to identify additional diagnostic symptoms. Ninety-two patients with operated carpal tunnel syndrome and 138 patients with spinal surgery for cervical spondylosis were reviewed. After exclusion of cases co-morbid with both cervical spondylosis and carpal tunnel syndrome or other neurological disorders, 44 patients with carpal tunnel syndrome and 41 patients with cervical spondylosis were compared. There were significant differences in the symptomatology between the two groups. In carpal tunnel syndrome, 84% had nocturnal paraesthesia, 82% hand paraesthesia were aggravated by hand activity, and hand pain occurred in 64%. The incidences were only 10%, 7% and 10%, respectively in cervical spondylosis. Neck pain was present in 76% of cervical spondylosis but only in 14% of carpal tunnel syndrome, and lower limb symptoms were present in 44% of cervical spondylosis and only 9% in carpal tunnel syndrome.

Ultrasound for the detection of vegetative foreign body in hand--a case report.

Foreign bodies in soft tissues are commonly encountered in daily orthopaedic practice. While most of the metals and glass foreign bodies can be detected by plain radiograph, organic substances such as wood and vegetative materials are radiolucent. Unfortunately, these radiolucent foreign bodies are usually more prone to cause an inflammatory reaction and infection. The detection can be even more difficult in cases of multiple foreign bodies and in penetrating injuries with small innocuous skin wounds. Ultrasonography is a sensitive and reliable investigation for detection of foreign bodies in soft tissue. We present a case of penetration injury to thumb with residual radiolucent foreign bodies and demonstrate the proper role of ultrasonography in the management of foreign bodies in soft tissues.