N-Methyl-(2S,4R)-trans-4-hydroxy-L-proline isolated Sideroxylon obtusifolium attenuates TPA-induced irritant contact dermatitis in mice.

Dermatitis is defined as a set of inflammatory diseases that affect the skin, with varied causes. Among the different types of dermatitis, contact dermatitis is the most prevalent. Although the current therapy is often effective, it is associated with adverse effects and the possibility of drug tolerance. N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline is a L-proline amino acid derivative found in the leaves of Sideroxylon obtusifolium, a species traditionally used to treat inflammatory diseases. The aim of this study was to investigate the topical anti-inflammatory effect of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis in mice. Topically administered NMP, at doses of 0.03 - 0.50 mg/ear, reduced TPA-induced ear edema and neutrophil migration, as evidenced by low tissue myeloperoxidase activity and verified by histological examination. In addition, NMP (0.06 mg/ear) reduced tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, INF-γ and MCP-1) and of the anti-inflammatory cytokine IL-10, and reduced gene expression of TNF-α, IL-6 and IL-1ß increased by TPA. The data suggest that N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline acts as a topical anti-inflammatory agent that decreases the expression of inflammatory cytokines, making it useful for the treatment of skin inflammation. Further investigations are necessary for its development as a therapeutic agent.

Prognostic determinants in severe odontogenic space infections: a single-center retrospective analysis.

BACKGROUND: Odontogenic space infections are a common presentation in oral and maxillofacial surgery units worldwide. Multiple patient and treatment dependent variables may be used predict the outcomes of the disease process. This study was aimed at a retrospective evaluation of significant predictors of prognosis in terms of length of hospital stay and the need for re-exploration in cases of odontogenic space infections. METHODS: Patients who underwent incision and drainage of odontogenic space infections were identified from the hospital records of the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, Karnataka, India. The variables assessed included Diabetic status, pyrexia on admission, topical rubefacient agent application, hot fomentation, recent tooth extraction, trismus, dysphagia or dyspnea on presentation, white blood cell count, number of spaces involved, antibiotics used, organisms isolated, severity of the infection and the anesthesia technique used (local anesthesia [LA], conscious sedation or general anesthesia). RESULTS: The sample consisted of 259 patients (110 male, 159 female) with a mean age of 41±16.9 years. Space infections were preceded by tooth extractions in 53 (20%) cases, rubefacient balm application in 130 (40%) and hot fomentation in 58 (22%) cases. Trismus was noted in 140 patients with an average mouth opening of 21±10.3 mm. Dyspnea and dysphagia were noted in 55 (21%) and 96 (37%) patients each. Sixty-six patients were diabetic. The average length of hospital stay was 5.8±3 days and re-exploration was required in 75 (29%) patients. Significant predictors of hospital stay were severity (P<0.001), number of spaces affected (P<0.001), hot fomentation (P=0.04), trismus (P<0.001), dysphagia (P<0.001) and dyspnea (P<0.001). Predictors of re-exploration are an increased primary surgery under LA (P<0.001), white blood cell count (P<0.001), rubefacient balm application (P=0.045), dysphagia (P<0.001), dyspnea (P=0.018), and reduced mouth opening (P<0.001). No significant correlation between diabetes and length of hospital stay or the need for re-exploration were found in this study. CONCLUSIONS: Poorer outcomes can be predicted based on the severity of the infection, the number of spaces involved, an increased white blood cell count as well as clinical signs and symptoms like trismus, dysphagia and dyspnea. Hot fomentation and Rubefacient agent application were identified as significant determinants of poor prognosis in this study. The presence of these indicators warrants a more aggressive approach towards management of space infections.

Chemotherapy Extravasation: Incidence of and Factors Associated With Events in a Community Cancer Center.

BACKGROUND: The administration of chemotherapy is a high-risk and nurse-sensitive practice. One complication is extravasation. OBJECTIVES: The purpose of this study was to determine the incidence of and iatrogenic factors associated with extravasation in the ambulatory and inpatient settings of a community cancer center. METHODS: Events were reviewed by agent, route of administration, patient characteristics, and RNs administering the agent. A one-year, retrospective review of electronic health records and pharmacy and nursing reports was conducted. FINDINGS: The number of vesicants, irritants, and irritants with vesicant properties administered was 12,260 in the ambulatory setting and 612 on the inpatient unit, with 21 and 1 extravasation events, respectively. Incidence rates for both settings were 0.001%. The most common agent to extravasate was docetaxel, and all events occurred via peripheral route. The incidence of events was lower than the reported benchmark for National Cancer Institute-designated cancer centers.

Topical hydrogel containing Achyrocline satureioides oily extract (free and nanocapsule) has anti-inflammatory effects and thereby minimizes irritant contact dermatitis.

Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.

Recommendations for Management of Noncytotoxic Vesicant Extravasations.

To prepare clinicians to treat extravasation of noncytotoxic vesicants with antidotes and thermal compresses, a literature review was performed to identify noncytotoxic vesicants and to create evidence and consensus-based recommendations. The stage of injury and vesicant's mechanism of tissue injury dictate treatment. For a vasopressor extravasation, warm compresses and administration of a vasodilator are recommended. For osmolarity, pH, absorption refractory, and cytotoxic concentration-dependent vesicants, warm compresses and administration of hyaluronidase are recommended. Compared with potentially catastrophic costs of undertreatment, the cost of overtreatment is minimal.

Cantharidin is Superior to Trichloroacetic Acid for the Treatment of Non-mucosal Genital Warts: A Pilot Randomized Controlled Trial.

Condyloma Acuminatum is a sexually transmitted viral disease caused by the human papilloma virus (HPV). It is the most common viral sexually transmitted disease. In this randomized controlled trial, cantharidin was found to be more effective and better tolerated than trichloroacetic acid for the treatment of these lesions. Patients treated with cantharidin healed with less scarring than those treated with TCA (P<0.034), had less pain during treatment (P<0.01), and required fewer treatments to eradicate warts (P<0.01) when compared to Trichloroacetic acid.

[Rapidly growing squamous cell carcinoma after ingenol mebutate treatment]. / Carcinome épidermoïde de croissance rapide après traitement par mébutate d'ingénol.

INTRODUCTION: Ingenol mebutate is an actinic keratosis treatment, which has a dual action mechanism. It allows a rapid cellular death and a severe inflammation. OBSERVATION: We report the case of a 75 years old patient with a rapidly growing tumor 5 weeks after application of ingenol mebutate on typical actinic keratosis. Histological analysis after surgical excision showed an invasive squamous cell carcinoma (SCC); with aggressiveness signs: perineural infiltration and vascular permeation. DISCUSSION: Ingenol mebutate's common side effects are benign and regressive within 2 to 4 weeks. There are erythema, edema, crusts, and ulcerations/erosions. Squamous cell carcinoma development was rarely reported. We have tried to collect other cases in the literature and in pharmacovigilance centres: three similar cases were recently published in the literature, 21 cases were notified to the European Medicines Agency and we asked French pharmacovigilance centres and found 5 cases of SCC after ingenol mebutate application. The role of the molecule in SCC development is currently unknown. Induced inflammation could take part in the development of these tumors. We compare this case with other situations of inflammation, such skin graft donor site or surgical incision, complicated of rapidly growing SCC. Our case, literature's and pharmacovigilance's cases encourage us to follow ingenol mebutate's side effects. Careful follow-up and registration of such cases are important to gain further insight on this topic.

Acute intensive care unit management of mustard gas victims: the Turkish experience.

PURPOSE: Sulphur mustard (SM) is an highly toxic and vesicant chemical weapon that was used in various military conflicts several times in the history. The severity of ocular, dermal, and pulmonary symptoms that may appear following a characteristic asymptomatic period are depending on the SM concentration and exposure duration. The aim of this study is to present the clinical features and share the intensive care unit (ICU) experiences for the medical management of mustard gas victims. MATERIALS AND METHODS: Thirteen Free Syrian Army soldiers near Al-Bab region of North Syria were reportedly exposed to oily blackish smoke with garlic smell due to the explosion of a trapped bomb without causing any blast or thermal effect on 26th November 2016. None of them wore any chemical protective suits or gas masks during explosion. Since they observed skin lesions including bullous formation next day, they were admitted to the Turkish Field Hospital at the Turkish - Syrian border and then evacuated to the State Hospital of Gaziantep Province, Turkey for further management. Eight victims who were very close to point of explosion suffered burning eyes, sore throat, dry cough and dyspnoea after the chemical attack. RESULTS: On admission to hospital, all cases had conjunctivitis, hoarseness and bullae on various body areas. Blepharospasm and opacity were found in 8 patients and 5 of them had corneal erosions and periorbital oedema. Temporary loss of vision in 4 cases lasted for 24 h. Multiple fluid-filled blisters were observed especially on the scalp, neck, arms and hands, where direct skin exposure to the agent occurred. A definitive clinical care and infection prophylaxis measures along with the burn treatment and bronchodilators for respiratory effects were applied in ICU. Two patients received granulocyte-colony-stimulating factor due to the SM-mediated bone marrow suppression on the 16th day of exposure and one of them died because of necrotic bronchial pseudomembrane obstruction resulting in cardiopulmonary arrest. CONCLUSIONS: SM was first used during the First World War and it is still considered one of the major chemical weapons recently used by non-state actors in Syria and Iraq. In case of SM exposure, medical treatment of SM-induced lesions is symptomatic because no antidote or causal therapy does exist even though SM is very well known for over 100 years. However, clinical management in intensive care medicine of SM victims have improved since the 1980s, this study which is one of the largest recent SM-exposed case series since that time is important for the contribution to the clinical experience.

Measuring niacin-associated skin toxicity (NASTy) stigmata along with symptoms to aid development of niacin mimetics.

Though cardioprotective, niacin monotherapy is limited by unpleasant cutaneous symptoms mimicking dermatitis: niacin-associated skin toxicity (NASTy). Niacin is prototypical of several emerging drugs suffering off-target rubefacient properties whereby agonizing the GPR109A receptor on cutaneous immune cells provokes vasodilation, prompting skin plethora and rubor, as well as dolor, tumor, and calor, and systemically, heat loss, frigor, chills, and rigors. Typically, NASTy effects are described by subjective patient-reported perception, at best semi-quantitative and bias-prone. Conversely, objective, quantitative, and unbiased methods measuring NASTy stigmata would facilitate research to abolish them, motivating development of several objective methods. In early drug development, such methods might better predict clinical tolerability in larger clinical trials. Measuring cutaneous stigmata may also aid investigations of vasospastic, ischemic, and inflammatory skin conditions. We present methods to measure NASTy physical stigmata to facilitate research into novel niacin mimetics/analogs, detailing characteristics of each technique following niacin, and how NASTy stigmata relate to symptom perception. We gave niacin orally and measured rubor by colorimetry and white-light spectroscopy, plethora by laser Doppler flowmetry, and calor/frigor by thermometry. Surprisingly, each stigma's abruptness predicted symptom perception, whereas peak intensity did not. These methods are adaptable to study other rubefacient drugs or dermatologic and vascular disorders.

Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation.

Conservative interventions with simple procedures and predictable benefits are expected by patients with recurrent dislocation of the temporomandibular joint (TMJ). We have introduced a modified technique of prolotherapy that comprises injection of lignocaine and 50% dextrose at a single site in the posterior periarticular tissues. We studied the effects in 45 younger patients (age range 17-59 years) with non-neurogenic recurrent dislocation of the TMJ, and confirmed the therapeutic effect after more than a year's follow-up. There were appreciable improvements in the number of episodes of dislocation and clicking after the injection. The overall success rate, defined as the absence of any further dislocation or subluxation for more than 6 months, was 41/45 (91%). Of the 41 rehabilitated patients, 26 (63%) required a single injection, 11 (27%) had 2 treatments, and 4 (10%) needed a third injection. All patients tolerated the injections well. The modified dextrose prolotherapy is simple, safe, and cost-effective for the treatment of recurrent dislocation of the TMJ.

Cantharidin combined with chemotherapy for Chinese patients with metastatic colorectal cancer.

BACKGROUND: This systematic analysis was conducted to evaluate the efficacy and safety of cantharidin combined with chemotherapy in treating Chinese patients with metastatic colorectal cancer. METHODS: Clinical studies evaluating the efficacy and safety of cantharidin combined with chemotherapy on response and safety for Chinese patients with colorectal cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. RESULTS: When cantharidin combined with chemotherapy, 4 clinical studies which included 155 patients with advanced colorectal cancer were considered eligible for inclusion. The systematic analysis suggested that, in all patients, pooled RR was 46.5% (72/155) in cantharidin combined regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia with cantharidin combined treatment; no treatment related deaths occurred. CONCLUSION: This systematic analysis suggests that cantharidin combined regimens are associated with high response rate and accepted toxicity in treating Chinese patients with metastatic colorectal cancer suggesting that randomized clinical trials are now warranted.

Oral myiasis--a case report.

Myiasis, a term introduced by William Hope in 1840, refers to the invasion of tissues and organs of animals and human wounds and certain body cavities by the dipteran larvae, which manifests as subcutaneous furunculoid or boil-like lesions. Oral myiasis is a rare pathology and a risk to the patient's life. A higher incidence is seen in rural areas, affecting the tropical and subtropical zones of Africa and America. It can be secondary to medical or anatomic conditions, such as cancrum oris, neglected mandibular fracture, cerebral palsy, mouth breathing, anterior open bite, incompetent lips, and use of mechanical ventilation. Myiasis also has been described after tooth extraction. All these conditions more easily allow the infestation of human tissues. Myiasis affecting the orodental complex is rare. This case report describes oral myiasis in a 25-year-old male patient who was a gardener by profession. The lesion was treated with turpentine oil, which forced the larvae out, and irrigated with normal saline solution.

Successful treatment of recurrent abdominopelvic neurenteric cysts by OK-432 injection.

The case of recurrent intraabdominal neurenteric cyst after surgical excision in an infant is described. After several operative resections, we changed therapeutic strategy and performed local injection of OK-432. Indeed, there is experience with the application of OK-432 for other entities, especially lymphangioma, but to our knowledge, there is no report published so far on the treatment of neurenteric cyst with OK-432. We describe for the first time an effective and simple treatment of recurrent neurenteric cyst.

Plantar warts: a focus on treatment modalities.

Plantar warts are a common problem frequently seen by dermatologists and other practitioners with an interest in skin disease management. The diagnosis is often straightforward, but the treatment is difficult and lengthy. The available treatment options are reviewed.

Thoracoscopic talc pleurodesis for recurrent, symptomatic pleural effusion following cardiac operations.

Seventeen patients who underwent a cardiac operation developed a recurrent, symptomatic pleural effusion ultimately requiring video-assisted thoracic surgery (VATS) and talc pleurodesis. These patients represented 0.4% of all patients undergoing a cardiac operation over the same time period. Compared with an age- and sex-matched control group of cardiac surgery patients, patients requiring VATS for recurrent pleural effusion were more obese with higher body mass index (31.9 +/- 1.2 versus 28.3 +/- 1.4 kg/M2, P = 0.03), were more likely to have undergone a complex cardiac operation (8/17 versus 1/17, P =.01) and were more frequently on anticoagulation and antiplatelet agents besides aspirin (8/17 versus 2/17, P =.02). Patients underwent 1.86 +/- 0.34 thoracenteses with drainage of 846 +/- 166 mL/thoracentesis prior to referral for VATS. On average, patients underwent VATS 4.83 +/- 1.49 months after their cardiac operation. There were 3 VATS-related complications (17.6%) and no deaths. VATS talc pleurodesis led to symptomatic and radiologic improvement in all patients with a mean follow-up of 8.2 +/- 1.5 months. VATS talc pleurodesis effectively and safely treats the unusual postcardiac surgery patient with refractory pleural effusion.

Beneficial and adverse effects of chemopreventive agents.

The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.

Larvicidal effects of mineral turpentine, low aromatic white spirits, aqueous extracts of Cassia alata, and aqueous extracts, ethanolic extracts and essential oil of betel leaf (Piper betle) on Chrysomya megacephala.

BACKGROUND: Many methods have been employed, with variable success, in the treatment of cutaneous myiasis caused by Chrysomya species. AIMS: Experiment 1: to assess the larvicidal effect of mineral turpentine (MT) and the main ingredient of MT, low aromatic white spirits (LAWS), on Chrysomya megacephala larvae in vitro. Experiment 2: to assess the larvicidal effects of aqueous extracts of winged senna (Cassia alata), and aqueous extracts, ethanolic extracts and essential oil of betel leaf (Piper betle). METHODS: In experiment 1, two samples of LAWS were obtained from two industrialists (samples 1 and 2). Adult flies of C. megacephala were bred in the insectory of the Department of Parasitology, Faculty of Medicine, University of Colombo. Petri dishes were prepared with pads of cotton wool. These cotton pads were soaked separately in MT, LAWS samples 1 and 2, and normal saline as a control. Ten larvae were placed in each Petri dish. The activity of the larvae was observed and recorded half-hourly. MT and the two samples of LAWS were analyzed by chromatography. In experiment 2, volatile essential oil of betel was prepared using a standard steam distillation process. An ethanolic extract of betel was obtained after boiling the crushed leaf with water, and mixing the stock with ethanol. Betel oil dilutions of 1-4% were prepared using 1% Tween 80 (v/v aq) as a solvent, with 0.05 g/100 mL sodium lauryl sulphate (as stabilizer) and 0.01 g/100 mL methyl paraben (as a preservative). Cotton wool swabs soaked in 1, 2, 3 and 4% essential oil of betel in 1% Tween 80 (v/v aq) prepared as above, 1, 2, 3 and 4% ethanolic extract of betel, 50 and 25% aqueous extract of C. alata, and 50 and 25% aqueous extract of betel were placed in separate Petri dishes. Ten larvae were placed in each Petri dish. 1% Tween 80 solvent with the stabilizer and the preservative, but without betel essential oil, was used as a negative control and MT was used as a positive control. Larval motility was assessed as before. RESULTS: MT and the two LAWS samples killed the larvae in vitro within 4 h. Chromatography showed more unidentified constituents in MT than in pure LAWS, indicating additional substances in MT. The 4 and 3% preparations of the essential oil of betel were effective in killing 100% of the larvae of Chrysomya within 3 h 30 min. The 2% extract of betel essential oil killed 96.7% of larvae in 4 h. Ethanolic and aqueous extracts of betel, the aqueous extract of C. alata, normal saline and the Tween 80 solvent were not larvicidal. CONCLUSIONS: MT and LAWS, the main ingredient of MT, were effective in killing Chrysomya larvae. Essential oil obtained from betel leaves also showed a dose-dependent larvicidal effect on Chrysomya larvae. This natural product may be effective in the treatment of wound myiasis.

Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene elicits a specific T cell-dependent immune response.

An empirically established chemoimmunotherapy for metastatic melanoma combines the systemic administration of the chemotherapeutic agent dacarbazine (DTIC) with the epifocal application of the contact sensitizer 2,4-dinitrochlorobenzene (DNCB) on cutaneous metastases. Although this therapy yields high response rates resulting in prolonged survival, the mechanisms involved remain unknown. Here, we investigated whether treatment of tumor-bearing mice with DTIC and DNCB resulted in a specific immune response against the tumor. Subcutaneous (s.c.) tumors and lung metastases were induced in C57BL/6 mice by injecting syngeneic B16-melanoma cells s.c. or into the lateral tail vein, respectively. Mice were treated with intraperitoneal injections of DTIC followed by epifocal application of DNCB. This therapeutic approach significantly reduced the growth of s.c. tumors as well as lung metastases. Our data showed that the effector mechanisms involved are dependent on T cells. No therapeutic effect was observed in immunodeficient RAG-1(-/-) mice, or when the contact sensitizer DNCB was replaced by skin irritants (croton oil or tributyltin). Splenic lymphocytes obtained from treated mice displayed a three-fold higher specific cytolytic activity against B16 cells than in tumor-bearing controls. Both CD8(+) and CD4(+) T cells were able to lyse B16 cells. No changes were observed in natural killer (NK) cell activity. Likewise, tumor-infiltrating lymphocytes (TIL) of treated mice showed higher cytolytic activity than that of controls. Analysis of cytokine expression in s.c. tumors revealed increased mRNA levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in treated tumors. Together, these findings demonstrate the ability of DTIC/DNCB treatment to induce an effective T cell-dependent host immune response against a syngeneic tumor.