Granulocyte and monocyte adsorptive apheresis for pyoderma gangrenosum.

Pyoderma gangrenosum (PG), a chronic aseptic inflammatory skin disease characterized by skin ulcers with elevated and undermined borders, is resistant to conventional therapies. PG is elicited by activated neutrophils and macrophages and is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, aortitis syndrome, and hematopoietic disorders. This single-center study assessed the efficacy and safety of selectively depleting myeloid-lineage leukocytes in patients with PG. Patients with PG, aged 20 or over, received 5 or 10 treatment sessions of granulocyte and monocyte adsorption apheresis (GMA), once or twice a week. Treatment efficacy was assessed based on the rate of skin ulcer reduction, the visual analog scale of pain, and the physician's global assessment of the skin lesions. A complete response (CR) was obtained in eight patients, a nearly complete response (nCR) in three patients, and a partial response (PR) in two patients. In four of the other six, the disease remained stable (SD) and in two we observed disease progression (PD). No severe adverse events were recorded. Our results suggest that GMA is a useful and safe treatment modality for PG.

Bilateral diffuse uveal melanocytic proliferation with mucocutaneous pigmentation.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome associated with extraocular malignancies. Extraocular pigmented lesions have been reported. We report that two patients with BDUMP presented with non-ocular pigmented lesions.

Clinical outcome of the chronic flexor tenosynovitis in the hand caused by non-tuberculous mycobacterium treated by extensive tenosynovectomy and drugs.

Chronic flexor tenosynovitis in the hand caused by non-tuberculous mycobacterial (NTM) infection is uncommon. Although some authors have recommended combining surgical and drug therapy, there are few reports about the timing of drug administration after operation. The purpose of this retrospective study was to analyse the clinical outcome of the protocol, which consisted of extensive tenosynovectomy and drug therapy administered after culture results had been obtained. Four men and one woman were included. Average age was 57.4 years and average follow-up period was 46.7 months. Extensive tenosynovectomy was performed and surgical specimen was examined histopathologically and microbiologically. After a positive culture result had been obtained, three kinds of drugs were administered. Clinical outcome including infectious condition, range of motion, and grip strength was examined. All patients were immunocompetent and had no underlying disease. Three patients were diagnosed at first operation and two were diagnosed at second operation. The average period of drug therapy was 5.5 months. In four patients, infection resolved with combination therapy. In one patient with surgical treatment, only swelling remained. Osteomyelitis of the scaphoid was found in one patient to whom systemic steroid had been administered because of a negative culture result at first operation. For immunocompetent patients, flexor tenosynovitis in the hand caused by NTM was resolved with a combination of surgical and drug treatment. Drug treatment seemed to be essential after a reduction of the infectious lesion and the timing of administration was safe enough to resolve in four patients.

Evaluation of a newly-developed immunochromatography strip test for diagnosing dermatophytosis.

BACKGROUND: Traditionally, dermatophytosis, a common disease affecting millions of people world-wide, has been diagnosed by direct microscopy and fungal culture. The immunochromatography (ICG) strip test was recently developed. METHODS: We compared the performance of the ICG strip test for the detection of dermatophytes in samples from human skin and nails with direct microscopy. The 160 samples, consisting of 88 skin and 72 nail specimens, were subjected to direct microscopy study using a 20% KOH solution and to examination with the ICG strip test. Of 160 samples, 18 were examined by fungal culture using Sabouraud dextrose agar medium. RESULTS: We found that the overall sensitivity and specificity of the ICG test were 83.5% and 66.7%; they were 82.1% and 76.2% for the 88 skin and 85.4% and 58.3% for the 72 nail specimens, respectively. CONCLUSIONS: Our findings indicate that the efficacy of the ICG test is comparable to direct microscopy for the detection of dermatophytes. Performance of the assay was easy, and results were available quickly. We suggest that it is an effective tool for dermatophytosis screening.

MK615, a Prunus mume Steb. Et Zucc ('Ume') extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1/2-Id-1 pathway.

The Japanese apricot, a commonly consumed food called 'Ume' in Japan, has been used for a traditional Japanese medicine for centuries. MK615, an extract of compounds from 'Ume', has strong antitumorigenic and antiinflammatory effects including the induction of apoptosis and autophagy, and inhibition of cytokine production mediated via the inhibition of MAPKs signaling including ERK-1/2, JNK and p38MAPK. The inhibitor of DNA binding 1 (Id-1), a basic helix-loop-helix (bHLH) transcription factor family, is essential for DNA binding and the transcriptional regulation of various proteins that play important roles in the development, progression and invasion of tumors. In melanoma, Id-1 is constitutively expressed in the late and early stages, suggesting it as a therapeutic target in patients with melanoma. This study reports that MK615 profoundly reduced both the mRNA- and protein expression levels of Id-1 and inhibited cell growth in A375 melanoma cells. MK615 markedly inhibited the phosphorylation of ERK1/2, which is associated with Id-1 protein expression in A375 cells. Id-1-specific RNAi induced the death of A375 cells. Moreover, the expression of Bcl-2 was decreased by both MK615 and Id-1-specific RNAi in A375 cells. The results suggest that MK615 is a potential therapeutic agent for treating malignant melanoma.

1,5-Anhydro-D-fructose: A natural antibiotic that inhibits the growth of gram-positive bacteria and microbial biofilm formation to prevent nosocomial infection.

Nosocomial infections caused by microbial opportunistic infections or microbial biofilms may occur during hospitalization and increase patient morbidity, mortality and health care costs. Artificial antibiotic agents were initially used to prevent infection; however, the high prevalence of nosocomial infections has resulted in their excessive use, which has led to microbial resistance to these agents. The increase in microbial resistance to antibiotics and the development of antibiotic agents may be the cause of the production of other microbial resistance. Thus, natural compounds that have no adverse side effects would be a preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose (1,5-AF), a natural plant compound derived from starch, has been found to have multifunctional properties, including antioxidant, antiplatelet aggregation by thrombin and anti-inflammatory activities. The results of the present study demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci on the hands as well as the growth of Staphylococcus epidermidis, which is a cause of opportunistic infections. Furthermore, 1,5-AF suppressed biofilm formation by the methicillin-resistant Staphylococcus aureus. In conclusion, 1,5-AF is a natural compound that may be effective in preventing nosocomial infections, without causing adverse side effects.

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction.

Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.

Edaravone: a new therapeutic approach for the treatment of acute stroke.

Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeutic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Meanwhile, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immediately administered on suspicion of acute stroke, including AIS and AHS.

Metastatic cutaneous squamous cell carcinoma treated successfully with surgery, radiotherapy and S-1/cisplatin chemotherapy.

Primary cutaneous squamous cell carcinoma (SCC) is a malignant tumor that arises from keratinizing cells of the epidermis or its appendages. We present a patient with cutaneous SCC on the left instep with metastases to multiple lymph nodes in the para-aortic, iliac and groin region. We chose a combination of surgery and concurrent chemoradiotherapy. The chemotherapeutic agent S-1/cisplatin was selected based on results of the histoculture drug response assay. The patient responded dramatically to this multidisciplinary treatment and complete remission was achieved.

ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB.

Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-L(alpha), an upstream signaling molecule of ER stress, decreased at 1-4h after 10 mJ/cm(2) irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm(2) UVB at 4h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.

Advanced malignant melanoma responds to Prunus mume Sieb. Et Zucc (Ume) extract: Case report and in vitro study.

Malignant melanoma (MM) is an aggressive chemoresistant skin cancer characterized by rapid metastasis and a poor prognosis. Therefore, the development of innovative effective therapies is critical. MK615 is an extract from the Japanese apricot Prunus mume Sieb. Et Zucc (Ume). At a neutral pH, it contains natural chemical substances such as triterpenoids that exert anti-neoplastic effects in several types of cancers. We found that in patients with advanced MM, MK615 dramatically suppressed the cutaneous in-transit metastasis of the disease. Pre- and post-treatment comparison of tumors showed that the apoptotic index was significantly increased by MK615. In vitro studies, MTT assay, flow cytometric cell cycle analysis and immunofluorescence microscopy revealed that MK615 inhibited the growth of SK-MEL28 cells in a dose-dependent manner, increased the proportion of cells in sub-G1 phase and induced apoptosis. We further examined the expression of the receptor for advanced glycation end products (RAGE). RAGE is a multi-ligand receptor that binds to a novel cytokine, high mobility group box protein 1 (HMGB1), as well as advanced glycation end products. There is evidence that RAGE/HMGB1 interactions enhance cell invasion in MM. Here, we present Western blotting and immunofluorescence microscopy data indicating that MK615 inhibited the expression of RAGE in SK-MEL28 cells, and suppressed the release of HMGB1 by SK-MEL28 cells. Our findings suggest that MK615 may be a valuable tool for treating MM and other malignant tumors.

Positive nasal culture of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for surgical site infection in orthopedics.

BACKGROUND: Although nasal carriage of MRSA has been identified as one of the risk factors for surgical site infection (SSI) with MRSA, there have been no reports of this in the orthopedics field. METHODS: This prospective observational cohort study included 2,423 consecutive patients who were admitted to our department over 26 months and who underwent orthopedic surgery. We examined the relationship between pre-existing nasal MRSA and subsequent occurrence of SSI with MRSA. RESULTS: 63 patients (2.6%) had a positive nasal MRSA culture. 15 patients (0.6%) developed SSI with MRSA. The occurrence of SSI with MRSA in nasal MRSA carriers was significantly higher than that in non-carriers (4 out of 63 (6.3%) vs. 11 out of 2,360 (0.5%); p < 0.001) (adjusted OR: 11; 95% CI: 3-37; p = 0.001). INTERPRETATION: We recommend appropriate treatment of patients who are nasal carriers of MRSA before orthopedic surgery.

Acetabular component orientation in intra- and postoperative positions in total hip arthroplasty.

INTRODUCTION: In total hip arthroplasty (THA), acetabular component orientation has critically important effects on dislocation, range of motion, polyethylene wear, pelvic osteolysis, and component migration. The differences in the pelvic orientation in the intraoperative lateral position for insertion of acetabular component during operation and that in the postoperative supine position for evaluation of acetabular component orientation will be one of the factors, which make outliers in acetabular component orientation. We compared acetabular component orientation between intraoperative lateral position and postoperative supine position in 100 consecutive primary THAs. MATERIALS AND METHODS: A total of 100 consecutive primary THAs (between October 2004 and December 2005) in 100 patients performed by a single surgical team were investigated. Intraoperative anteroposterior radiographs of pelvis in the lateral position and postoperative anteroposterior radiographs of pelvis in the supine position were taken. Acetabular component orientation (vertical tilt and anteversion) were measured using computer software. RESULTS: The absolute values of difference between measurements in the two positions were 5.3 degrees +/- 4.5 degrees (mean +/- SD) for vertical tilt and 5.1 degrees +/- 3.7 degrees for anteversion. The difference in the vertical tilt between the two positions was significant (P < 0.0001). CONCLUSION: The difference in the acetabular component orientation between the two positions, which might be caused by the difference between intra- and postoperative pelvic orientation, should be considered during THA.

Wear particle analysis of highly crosslinked polyethylene isolated from a failed total hip arthroplasty.

Polyethylene wear particles are one of the most important factors affecting the results of total hip arthroplasty (THA). To reduce wear generation and to achieve better long-term results of THA, highly crosslinked polyethylene (HXPE) has recently been introduced and come into wide use. Thus far, however, there have been no reports on in vivo analysis of HXPE wear particles. We isolated HXPE wear particles from periprosthetic tissue of a failed THA and analyzed using scanning electron microscope. The number of particles was 5.33 x 10(7) g(-1). Particle size (equivalent circle diameter) was 0.66 +/- 0.40 microm (mean +/- standard error). Aspect ratio and roundness were 1.37 +/- 0.26 and 1.44 +/- 0.67, respectively. All the particles were round shaped, and "fibrils" or "shreds" were not detected. Thus far, this was the first report on in vivo wear particle analysis of HXPE. HXPE generated less, smaller, and rounder particles, compared with the corresponding reported values for particles generated from conventional polyethylene. These characteristics might affect macrophage response, osteolysis, and long-term results of THA with HXPE.

Flexion gap preparation opens the extension gap in posterior cruciate ligament-retaining TKA.

It has been reported that preparation of the flexion gap results in significant widening of the prepared extension gap in posterior stabilized (PS) total knee arthroplasty (TKA). To date, there is a paucity of data regarding cruciate ligament-retaining (CR) TKA. Changes in the extension gap caused by preparation of the flexion gap were measured in 42 varus osteoarthritic knees undergoing CR TKA. The extension gap was first prepared and then measured before and after preparation of the flexion gap. The extension gap increased significantly on both the medial and lateral sides (18.8-20.0 and 21.7-22.7 mm, respectively) (P < 0.01). Preparation of the flexion gap also resulted in significant widening of the extension gap on CR TKA. However, amount of extension gap increase in CR TKA was smaller than previous reports on PS TKA.

Blood management for patients with hemoglobin level lower than 130 g/l in total knee arthroplasty.

INTRODUCTION: The risk of requiring allogeneic blood transfusion after total knee arthroplasty has been recently decreased with several methods such as blood donation, blood salvage, and hematinic. For patients with a low baseline hemoglobin level, however, the rate of allogeneic transfusion is still high, and an effective method for avoiding allogeneic blood transfusion has not been established. We introduced intra- and postoperative blood salvage with the Cell Saver for patients with a baseline hemoglobin level lower than 130 g/l and analyzed the frequency of allogeneic blood transfusion. MATERIALS AND METHODS: From 1993 to 1997, 218 consecutive total knee arthroplasties were performed, and 155 knees with baseline hemoglobin lower than 130 g/l were included in this study. Baseline hemoglobin ranged from 62 to 129 g/l, with a mean of 110 g/l. All patients were managed with intra- and postoperative blood salvage with the Cell Saver. Preoperative autologous blood donation and/or use of hematinic was performed for 129 knees (group 1) and was not performed for 26 knees (group 2). There were no significant differences between the two groups with regard to preoperative factors. To examine the role of perioperative factors (age, sex, baseline hemoglobin level, revision procedure, preoperative blood donation, and use of hematinic) in determining the requirements for allogeneic transfusion, backward elimination logistic regression analysis was used. RESULTS: Seven knees (4.5%) required allogeneic transfusion. Group 1 (2.3%) exhibited a lower rate of allogeneic blood transfusion than group 2 (15.4%) (p=0.016). Hemoglobin levels on the day (p=0.016), 1 week (p=0.0001), and 2 weeks (p=0.007) after surgery were lower in group 1 than in group 2. Backward elimination logistic regression analysis showed that preoperative blood donation (p=0.048) and use of hematinic (p=0.040) were significantly associated with a requirement for allogeneic blood transfusion. CONCLUSION: Preoperative blood donation and use of hematinic were associated with a low incidence of allogeneic blood transfusion after total knee arthloplasty with intra- and postoperative blood salvage, even for patients with a baseline hemoglobin level below 130 g/l.

Deviation of a finger at the proximal interphalangeal joint caused by juxta-articular exostosis.

An exostosis around the interphalangeal joint can cause deformity of a finger. We present two children with deviated fingers as a result of exostoses that developed near the proximal interphalangeal joints and were successfully treated by resection and closed wedge osteotomy.

Lateral atlantoaxial joint arthrography in atlantoaxial rotatory fixation.

There has been much debate about the pathogenesis of atlantoaxial rotatory fixation. Intraarticular abnormality has not been well documented thus far. This is the first case of chronic atlantoaxial rotatory fixation in which atlantoaxial joints were examined by consecutive arthrography. A 7-year-old girl was diagnosed with atlantoaxial rotatory fixation on a three-dimensional CT scan. Arthrography of the lateral atlantoaxial joints indicated a rupture of the joint capsule on the dislocated side at first, followed by a successful repair after 5 weeks' immobilization with a halo apparatus. Because torticollis recurred after taking off the halo vest, we performed surgery in which severe adhesion of the cartilage surface of facet joint was noted on the undislocated side and release of the adhesion was needed to mobilize the atlas. Atlantoaxial arthrodesis by screw fixation facilitated a solid fusion of the segment.