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.

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.

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.

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.

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.

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.

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 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.

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.

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.

Local vs systemic corticosteroids in the treatment of carpal tunnel syndrome.

The authors compared the effectiveness of low-dose, short-term oral prednisolone vs local methylprednisolone injection in a prospective, double-blinded, parallel treatment study of carpal tunnel syndrome (CTS). A single injection of 15 mg methylprednisolone resulted in significant improvement in global symptom scores over a 12-week period. This study demonstrated the superiority of local steroid injection to oral steroid in the treatment of CTS.

Oscillations in the power spectra of motor unit signals caused by refractoriness variations.

The refractory period of a motor unit is an important mechanism that regulates the motor unit firing, and its variation has been found in many physiological cases. In this study, a new observation that an increase in the motor unit refractoriness results in an enhancement of oscillations, or ripple effects, in the motor unit output power density spectra (PDS) has been identified and studied. The effects of the refractoriness variation on the PDS of motor unit firing were investigated on three levels: theoretical modeling, simulation and electromyographic (EMG) experimentation on human subjects. Both theoretical modeling and simulation showed the enhanced oscillations, ripple effects, in MUAPT PDS, given the increase in the refractoriness. It was also found that the extent of the increment in output PDS oscillation could be related to the motor unit size and the mean firing rate of the stimulation. A needle EMG experiment on biceps brachii muscles of five healthy human subjects was carried out during isometric contraction at 20% maximum voluntary contraction (MVC) for 20 s with a fatigue effort proceeded by MVC. The increased oscillations in the PDS of the real MUAPTs were observed with the rising of the motor unit refractoriness due to fatigue. The study gives new information for EMG spectra interpretation, and also provides a potential method for accessing neuromuscular transmission failure (NTF) due to fatigue during voluntary contraction.

Alteration of patellofemoral contact during healing of canine patellar tendon after removal of its central third.

Alterations of the patellofemoral (PF) contact pressure and area were assessed using pressure-sensitive film after the removal of the central third of patellar tendon (PT) with healing over time in twelve dogs. The contralateral knee served as control. Histological sections were prepared for descriptive evaluation. No alterations in PT strain, PF contact pressure and area were measured immediately after the removal of the central third of PT compared with that before its removal. Compared with contralateral control, the healing of the donor PF induced a significantly increased PF contact area but not PF contact pressure in the specimens harvested at 6, 12, and 18 months after operation. Increased PF contact area indicated a proximal shift of the PF joint contact during flexion, which was associated with an increased strain of the healing PT under loading. The healing PT became hypertrophic compared with control, but the differences in the cross-sectional area were reduced over time. Histologically, a poorly organized extracellular matrix was observed at 6 months, with a progressive improvement in collagen fiber alignment up to 18 months postoperatively. The results of this study suggest that the removal of the central third of PT does not immediately change PF contact pressure and areas. However, remodeling of the healing tendon may cause an elongated PT, resulting in an increase in PF contact area under a given quadriceps force by knee extension.

Reconstruction of shoulder function using a reflected long head biceps: a moment arm study.

A tendon transfer technique is proposed for the reconstruction of the paralyzed shoulders secondary to brachial plexus injury. This innovative technique does not require bone-to-bone or tendon to-bone fixation, and attempts to overcome other clinical limitations such as those due to insufficient length of donor muscle. The approach is referred to as the reflected long head biceps (RLHB) technique. The long head of biceps tendons is utilized as a bridging tendon graft. Two surgical alternatives, namely the through-deltoid (TD) pathway and the sub-deltoid (SD) pathway, were studied. The moment arms of the transferred tendons were assessed and reported. The TD technique yielded a larger moment than the SD technique. In the plane 30 degrees anterior to the scapular plane, the average moment arms were 3.8cm TD and 3.0cm SD at zero elevation. Such differences tended to further widen with increasing elevation. At 80 degrees elevation, the moment arms became 3.2cm TD and 1.2cm SD. The results supported the clinical feasibility of this RLHB tendon transfer approach.

Carpal tunnel release. A prospective, randomised study of endoscopic versus limited-open methods.

Endoscopic carpal tunnel release has the advantage over open release of reduced tissue trauma and postoperative morbidity. Limited open carpal tunnel release has also been shown to have comparable results, but is easier to perform and is safer. We have compared the results of both techniques in a prospective, randomised trial. Thirty patients with bilateral carpal tunnel syndrome had simultaneous bilateral release. The technique of release was randomly allocated to either two-portal endoscopic release (ECTR) or limited open release using the Strickland instrumentation (LOCTR). The results showed that the outcome was similar at follow-up of one year using both techniques. However, the LOCTR group had significantly less tenderness of the scar at the second and fourth postoperative week (p < 0.01). There was also less thenar and hypothenar (pillar) pain after LOCTR. Subjective evaluation showed a preference for LOCTR.

Delivery of medication by iontophoresis to treat post-burn hypertrophic scars: investigation of a new electronic technique.

At present, direct current (DC) and pulsed direct current (PDC) methods are used for iontophoresis. Although the DC field has high efficiency, it exhibits some side-effects. The PDC field has little side-effects, but the efficiency is lower. In this study, a new iontophoretic drug device was designed for providing the maximal efficiency with the minimal side-effects. Tests of animal and human models showed that the permeation rate of the new field was higher than that of PDC and DC fields, and side-effects were lower than that of the DC field.

The cutometer and ultrasonography in the assessment of postburn hypertrophic scar--a preliminary study.

Sixteen patients with various degrees of postburn hypertrophic scars were evaluated by ultrasonography and elastometry. An Aloka Echo Camera (SSD-500) with a 7.5 MHz probe and a Cutometer SEM 575 skin elastometer were used. Serial monthly examinations were performed using both pieces of equipment. In some patients, more than one scar was assessed. The assessments were correlated with clinical grading of the progress of the scars. It was noted that ultrasonography was very sensitive in the localization of scar tissues, distinguishing them from normal skin, assessment of thickness and also delineation of the extent of scar tissues. The subcutaneous part of the scar could be assessed. Cutometer SEM 575 is a new machine that applies a gentle suction to the skin to measure its viscoelasticity. It is sensitive, the inter-observer variation is low, and it could be used for the grading of a scar. These two assessment techniques compliment other methods of scar assessment and will prove useful when assessment of response to treatment is required.