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Sample records for pre-existing pyoderma gangrenosum

  1. Vegetative pyoderma gangrenosum.

    PubMed

    Kim, Randie H; Lewin, Jesse; Hale, Christopher S; Meehan, Shane A; Stein, Jennifer; Ramachandran, Sarika

    2014-12-16

    Vegetative pyoderma gangrenosum is a rare, superficial variant of pyoderma gangrenosum that is more commonly found on the trunk as single or multiple, non-painful lesions. There is typically no associated underlying systemic disease. Compared to classic pyoderma gangrenosum, vegetative lesions are more likely to heal without the use of systemic glucocorticoids, although up to 39% of patients required a short course of prednisone in a review of 46 cases. Treatments for vegetative pyoderma gangrenosum include topical and intralesional glucocorticoids, minocycline or doxycycline, dapsone, colchicine, and, rarely, alternative steroid-sparing immunosuppressants. We present a case of multiple vegetative pyoderma gangrenosum lesions arising in prior surgical sites in a patient found to have IgA monoclonal gammopathy and abnormal urinary protein electrophoresis.

  2. Sporotrichosis masquerading as pyoderma gangrenosum.

    PubMed

    Spiers, E M; Hendrick, S J; Jorizzo, J L; Solomon, A R

    1986-06-01

    A 46-year-old man was diagnosed as having pyoderma gangrenosum after special stains and cultures from a skin biopsy specimen were reported as negative. Cutaneous sporotrichosis is usually diagnosed with relative ease on the basis of clinicopathologic features and prompt growth of the fungus in culture, although organisms are difficult to detect in tissue even with special stains. Identification of Sporothrix schenckii was delayed for three months in this patient because of unusual growth characteristics noted in the culture. The report of this patient's clinical course illustrates both the need to frequently reassess the diagnosis of pyoderma gangrenosum in treatment-resistant patients and the fact that S schenckii may be difficult to diagnose clinically and mycologically if the growth characteristics of the fungus are unusual.

  3. Pyoderma gangrenosum masquerading as Donovanosis

    PubMed Central

    Pai, Varadraj V.; Kikkeri, Naveen Narayanshetty; Athanikar, S. B.; Myageri, Anil; Rai, Vijetha

    2014-01-01

    Pyoderma gangrenosum (PG) is a rare inflammatory disorder of unknown etiology characterized by neutrophilic infiltration of the dermis and destruction of tissue. PG is diagnosed after excluding more commonly occurring condition presenting with similar manifestation. Though PG has been reported to occur over the genitalia, it rarely presents with concurrent involvement of the groin. Herein, we present a case of PG masquerading as Donovanosis. PMID:26396454

  4. Pyoderma Gangrenosum Simulating Necrotizing Fasciitis

    PubMed Central

    de Souza, Erik Friedrich Alex; da Silva, Guilherme Almeida Rosa; dos Santos, Gustavo Randow; Motta, Heloisa Loureiro de Sá Neves; Cardoso, Pedro Afonso Nogueira Moisés; de Azevedo, Marcelo Costa Velho Mendes; Pires, Karina Lebeis; Motta, Rogerio Neves; Silva, Walter de Araujo Eyer; Ferry, Fernando Raphael de Almeida; Pinto, Jorge Francisco da Cunha

    2015-01-01

    Pyoderma gangrenosum received this name due to the notion that this disease was related to infections caused by bacteria in the genus Streptococcus. In contrast to this initial assumption, today the disease is thought to have an autoimmune origin. Necrotizing fasciitis was first mentioned around the fifth century AD, being referred to as a complication of erysipelas. It is a disease characterized by severe, rapidly progressing soft tissue infection, which causes necrosis of the subcutaneous tissue and the fascia. On the third day of hospitalization after antecubital venipuncture, a 59-year-old woman presented an erythematous and painful pustular lesion that quickly evolved into extensive ulceration circumvented by an erythematous halo and accompanied by toxemia. One of the proposed etiologies was necrotizing fasciitis. The microbiological results were all negative, while the histopathological analysis showed epidermal necrosis and inflammatory infiltrate composed predominantly of dermal neutrophils. Pyoderma gangrenosum was considered as a diagnosis. After 30 days, the patient was discharged with oral prednisone (60 mg/day), and the patient had complete healing of the initial injury in less than two months. This case was an unexpected event in the course of the hospitalization which was diagnosed as pyoderma gangrenosum associated with myelodysplastic syndrome. PMID:26783395

  5. Cutaneous Blastomycosis Masquerading as Pyoderma Gangrenosum

    PubMed Central

    Azar, Marwan M.; Relich, Ryan F.; Schmitt, Bryan H.; Spech, Robert W.

    2014-01-01

    Cutaneous blastomycosis (CB) is associated with a variety of skin manifestations. Among other entities, CB may be mistaken for pyoderma gangrenosum due to overlap of findings on histopathologic examination. We report a case of CB, initially diagnosed as pyoderma gangrenosum and treated with steroids, leading to disseminated blastomycosis and acute respiratory distress syndrome (ARDS). PMID:24501027

  6. Cutaneous blastomycosis masquerading as pyoderma gangrenosum.

    PubMed

    Azar, Marwan M; Relich, Ryan F; Schmitt, Bryan H; Spech, Robert W; Hage, Chadi A

    2014-04-01

    Cutaneous blastomycosis (CB) is associated with a variety of skin manifestations. Among other entities, CB may be mistaken for pyoderma gangrenosum due to overlap of findings on histopathologic examination. We report a case of CB, initially diagnosed as pyoderma gangrenosum and treated with steroids, leading to disseminated blastomycosis and acute respiratory distress syndrome (ARDS).

  7. Vulvovaginal pyoderma gangrenosum secondary to rituximab therapy.

    PubMed

    Dixit, Shreya; Selva-Nayagam, Priya; Hamann, Ian; Fischer, Gayle

    2015-01-01

    Rituximab is being used increasingly for the treatment of B-cell malignancies and nonmalignant conditions. Pyoderma gangrenosum is a rare neutrophilic dermatosis, which can be either idiopathic or associated with underlying systemic inflammatory conditions. We present a series of 4 patients who presented with ulcerative pyoderma gangrenosum in the vulvovaginal area after treatment with rituximab.

  8. Pyoderma gangrenosum induced by episiotomy.

    PubMed

    Alani, Angela; Sadlier, Muriel; Ramsay, Bart; Ahmad, Kashif

    2016-01-19

    We present a patient who developed genital ulceration within hours following episiotomy procedure during a normal vaginal delivery. This was initially treated by the gynaecology and medical team as cellulitis with no improvement. A diagnosis of pyoderma gangrenosum (PG) was made by the dermatology team 12 days later. On further investigation, she was found to be hepatitis C positive. We report this case to highlight the phenomenon of pathergy and frequent misdiagnosis of PG by other medical teams. When a postsurgical wound is not healing despite relevant systemic treatment, the clinician should suspect PG as an early diagnosis and treatment is crucial.

  9. Peripheral Ulcerative Keratitis with Pyoderma Gangrenosum

    PubMed Central

    Imbernón-Moya, Adrián; Vargas-Laguna, Elena; Aguilar, Antonio; Gallego, Miguel Ángel; Vergara, Claudia; Nistal, María Fernanda

    2015-01-01

    Pyoderma gangrenosum is an unusual necrotizing noninfective and ulcerative skin disease whose cause is unknown. Ophthalmic involvement in pyoderma gangrenosum is an unusual event. Only a few cases have been reported, from which we can highlight scleral, corneal, and orbital cases. Peripheral ulcerative keratitis is a process which destroys the peripheral cornea. Its cause is still unknown although it is often associated with autoimmune conditions. Pyoderma gangrenosum should be included in the differential diagnosis of peripheral ulcerative keratitis. Early recognition of these manifestations can vary the prognosis by applying the appropriate treatment. We introduce a 70-year-old woman who suffered pyoderma gangrenosum associated with peripheral ulcerative keratitis in her left eye. The patient's skin lesions and peripheral keratitis responded successfully to systemic steroids and cyclosporine A. PMID:26527531

  10. Pyoderma Gangrenosum in the Urologist Clinic

    PubMed Central

    Ludwig, Dina J.; Roshani, Hossain; Steffens, Martijn G.; Moll, Frederik C.; Teepe, Robertus G.

    2016-01-01

    Pyoderma gangrenosum is a rare non-infectious skin disorder. It is often associated with systemic diseases, like the inflammatory bowel disease, rheumatological disease and (hematological) malignancy. The diagnosis is affirmed through a process of elimination and is principally based on clinical presentation and course. We present a 59-year-old male with T-cell large granular lymphocyte leukemia and pyoderma gangrenosum of penis and scrotum. Finally the patient was successfully treated with systemic prednisolone. PMID:27867335

  11. Pyoderma gangrenosum: A clinician's nightmare

    PubMed Central

    Bhaskaran, Bindhu; Mathew, Mittu John; Vijayan, K. N.; Zacharia, Asha

    2016-01-01

    Pyoderma gangrenosum (PG) is a rare disease and that affecting specifically the sole of the foot, is even rarer. Here, we report the case of a 54-year-old female admitted with a painful ulcer on the sole of the right foot which was initially treated with empirical antibiotics and debridement. The disease was found to spread rapidly after each debridement. The culture reports were negative; rheumatology workup and Doppler study were within normal limits. A clinical suspicion of PG was made and was confirmed with tissue biopsy. She was started on oral steroids following which she dramatically improved. Thus, when a patient presents with a rapidly expanding painful ulcer in a vascular limb that is refractory to antibiotic treatment and exacerbating on debridement, it is imperative to consider the possibility of PG. PMID:28217611

  12. Pyoderma Gangrenosum:Recognition and Management.

    PubMed

    Pompeo, Matthew Q

    2016-01-01

    Pyoderma gangrenosum is an unusual cause of skin ulcerations that wound specialists must be prepared to recognize. There is no diagnostic test since it is a diagnosis of exclusion, and if the disease is not recognized it can quickly become much worse. Pathergy, whereby a lesion begins or worsens due to trauma, such as a scrape, bite, debridement, surgery, or biopsy, is seen with pyoderma and requires special consideration. This case series and review will summarize the salient features of pyoderma and its treatment with an emphasis on the controversial role of surgery with pyoderma.

  13. Pyoderma gangrenosum: a systematic review.

    PubMed

    Cozzani, E; Gasparini, G; Parodi, A

    2014-10-01

    Pyoderma gangrenosum (PG) is a rare, chronic neutrophilic dermatosis of unknown etiology. The world wide incidence is estimated to be around 3-10 cases per million population per year. In 50-70% of cases inflammatory bowel diseases, hematological malignancies or rheumatologic disorders are associated to PG. Although the etiology is uncertain, the dysregulation of the immune system appears to be implied. Pathergy is the most important triggering factor of PG. Indeed, 20-30% of patients report the onset of PG following trivial trauma. Four main variants of PG have been described, namely classic, pustular, bullous, and vegetative forms. The classic form of PG is characterized by ulcers with a raised, undermined, inflammatory border. Intense pain is generally associated to PG. The diagnosis is mainly clinical and of exclusion. The differential diagnosis should take into account infections, vascular disorders and malignancies. The clinical course can be explosive and rapidly progressive or indolent and gradually progressive. Often patients develop only one episode and the overall prognosis is good but extremely influenced by the underlying disorders. Local therapy, mainly with topic steroids is used for mild to moderate lesions. For severe forms of PG a systemic therapy with glucocorticoids and/or other drugs such as tacrolimus, cyclosporine, etc. is needed. This paper is a systematic review of literature on PG.

  14. Pyoderma gangrenosum: challenges and solutions

    PubMed Central

    Gameiro, Ana; Pereira, Neide; Cardoso, José Carlos; Gonçalo, Margarida

    2015-01-01

    Pyoderma gangrenosum (PG) is a rare disease, but commonly related to important morbidity. PG was first assumed to be infectious, but is now considered an inflammatory neutrophilic disease, often associated with autoimmunity, and with chronic inflammatory and neoplastic diseases. Currently, many aspects of the underlying pathophysiology are not well understood, and etiology still remains unknown. PG presents as painful, single or multiple lesions, with several clinical variants, in different locations, with a non specific histology, which makes the diagnosis challenging and often delayed. In the classic ulcerative variant, characterized by ulcers with inflammatory undermined borders, a broad differential diagnosis of malignancy, infection, and vasculitis needs to be considered, making PG a diagnosis of exclusion. Moreover, there are no definitively accepted diagnostic criteria. Treatment is also challenging since, due to its rarity, clinical trials are difficult to perform, and consequently, there is no “gold standard” therapy. Patients frequently require aggressive immunosuppression, often in multidrug regimens that are not standardized. We reviewed the clinical challenges of PG in order to find helpful clues to improve diagnostic accuracy and the treatment options, namely topical care, systemic drugs, and the new emerging therapies that may reduce morbidity. PMID:26060412

  15. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    PubMed Central

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics. PMID:25024856

  16. Atypical pyoderma gangrenosum mimicking an infectious process.

    PubMed

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  17. Extensive phlegmon and pyoderma gangrenosum: diagnostic difficulties

    PubMed Central

    Wcisło-Dziadecka, Dominika; Brzezińska-Wcisło, Ligia; Arasiewicz, Hubert

    2015-01-01

    Pyoderma gangrenosum (PG) is a relatively rare neutrophilic dermatosis, characterized by progressive skin necrosis. It typically has a chronic course, of unknown etiology. Pyoderma gangrenosum diagnosis can be difficult because both histopathological examination and results of additional laboratory tests are not specific and the clinical state is conclusive, as for other physicians it poses a number of diagnostic dilemmas. Therefore, this condition should be treated interdisciplinary. We present a case of a 40-year-old patient with a diagnosis of PG, which in the early stages of the disease was treated as an extensive phlegmon by physicians of other specialties and it presented a serious diagnostic as well as therapeutic problem. PMID:25821427

  18. Factitious Ulcer Misdiagnosed as Pyoderma Gangrenosum.

    PubMed

    Conde Montero, Elena; Sánchez-Albisua, Begoña; Guisado, Soledad; Ángeles Martín-Díaz, María; Balbín-Carrero, Eva; Valdivelso-Ramos, Marta; de la Cueva Dobao, Pablo

    2016-02-01

    Dermatitis artefacta may represent a real challenge for the clinician. As the patient does not admit self-inflicting the lesions, misdiagnosis with other diseases, such as pyoderma gangrenosum, is common. Consequently, these patients normally go through unnecessary tests and receive potentially harmful treatments as clinicians determine their diagnosis. The authors present the case of a recurrent factitious abdominal ulcer that was initially diagnosed and treated as pyoderma gangrenosum. This report focuses on the necessity of suspecting dermatitis artefacta when morphology, history, and treatment failures are difficult to explain. It is essential to establish a supportive and confident approach and avoid initial confrontation. In-patient treatment may be useful and long-term followup may prevent recurrences.

  19. Pyoderma gangrenosum following autologous breast reconstruction

    PubMed Central

    Tuffaha, Sami H.; Robbins, Sanford H.; Bonawitz, Steven C.

    2017-01-01

    Pyoderma gangrenosum (PG) is an uncommon disorder characterized by the development of painful cutaneous ulceration, commonly precipitated by dermal injury at surgical sites. It is a diagnostic challenge as it manifests as necrotizing wounds which are commonly misdiagnosed as postoperative wound infection or ischemia. We discuss the clinical features and histopathological findings that allow for rapid identification of PG following autologous breast reconstruction and suggest an algorithm to aid diagnosis. PMID:28210559

  20. Pyoderma gangrenosum following autologous breast reconstruction.

    PubMed

    Singh, Prateush; Tuffaha, Sami H; Robbins, Sanford H; Bonawitz, Steven C

    2017-02-01

    Pyoderma gangrenosum (PG) is an uncommon disorder characterized by the development of painful cutaneous ulceration, commonly precipitated by dermal injury at surgical sites. It is a diagnostic challenge as it manifests as necrotizing wounds which are commonly misdiagnosed as postoperative wound infection or ischemia. We discuss the clinical features and histopathological findings that allow for rapid identification of PG following autologous breast reconstruction and suggest an algorithm to aid diagnosis.

  1. [Developments in pyoderma gangrenosum therapy in 2015].

    PubMed

    Modiano, P

    2015-01-01

    Diagnosis of pyoderma gangrenosum in 2014 continues to be made on clinical grounds, with the main form comprising an ulcer having poorly delineated purplish edges. The diagnostic criteria have been recently modified so as to rule out differential diagnoses (10% of retrospective series of pyoderma patients). The condition is commonly associated with other diseases (75%) such as emerging endocrine diseases (36.7%), and classical gastrointestinal, rheumatological and haematological diseases. The new concepts of PAPA and PASH syndromes, belonging to the category of auto-inflammatory diseases, provide new therapeutic perspectives. Corticosteroids continue to be the first-line therapy, along with immunosuppressant drugs in the event of steroid dependence. Second-line treatments consisting biotherapies show promise and interleukin-1 inhibitors have exhibited potential against pyoderma syndrome.

  2. Pyoderma gangrenosum due to lenalidomide use for multiple myeloma.

    PubMed

    Dasanu, Constantin A; Bockorny, Bruno; Alexandrescu, Doru T

    2015-12-01

    Pyoderma gangrenosum has been described in association with multiple myeloma and usually affects patients with active/untreated disease. This dermatologic condition was shown to resolve after successful anti-myeloma therapy. We report herein occurrence of pyoderma gangrenosum involving bilateral knees in a patient with multiple myeloma responding to lenalidomide therapy. Previous papers claimed usefulness of thalidomide and its newer derivatives for the therapy of this neutrophilic dermatosis. Occurrence of pyoderma gangrenosum in a myeloma patient responding to lenalidomide would argue against its effectiveness in treating this skin condition. Moreover, the clinical setting suggested that lenalidomide either induced or contributed to the occurrence of pyoderma gangrenosum in our patient. If our hypothesis is correct, we expect more reports of pyoderma gangrenosum with the use of this class of pharmaceuticals.

  3. Postoperative pyoderma gangrenosum: a rare complication after appendectomy.

    PubMed

    Faghihi, G; Abtahi-Naeini, B; Nikyar, Z; Jamshidi, K; Bahrami, A

    2015-01-01

    Pyoderma gangrenosum (PG) is an uncommon inflammatory ulcerative skin disease. It is characterized by painful progressive necrosis of the wound margins. Rarely, postoperative pyoderma gangrenosum (PPG) manifests as a severe disturbance of wound healing following surgical interventions. Only rare cases of this complication have been reported after appendectomy. We report a case of PPG in a 29-year-old female after appendectomy. She was successfully treated with oral prednisolone. Postoperative pyoderma gangrenosum should be kept in mind in the differential diagnosis of any postoperative delayed wound healing, because this disease is simply distinguished from a postoperative wound.

  4. Pathophysiology of pyoderma gangrenosum (PG): an updated review.

    PubMed

    Braswell, Sara F; Kostopoulos, Tassia C; Ortega-Loayza, Alex G

    2015-10-01

    Pyoderma gangrenosum is a challenging skin condition to identify and treat because of its multifactorial pathogenesis. It is a rare cutaneous manifestation diagnosed clinically by exclusion of infection, neoplasia, thrombophilia, and other inflammatory conditions. Pathogenetic and treatment studies are scarce. Abnormalities in the function of inflammatory cytokines, the immune system, and neutrophils combined with specific genetic mutations predispose patients to develop this complex disease process. Early recognition of patients at risk for pyoderma gangrenosum, the necessity to improve its early diagnosis, and the future outlook of targeted and personalized therapies relies on the improved comprehension of the complex pathogenesis of pyoderma gangrenosum.

  5. Fatal pyoderma gangrenosum with pathergy after coronary artery bypass grafting.

    PubMed

    Bryan, Charles S

    2012-01-01

    Surgeons and others who perform invasive procedures should be aware of the possibility of pyoderma gangrenosum and the risk of pathergy in patients who have a history of unexplained skin ulcers or poor wound-healing. We report the case of a 70-year-old man in whom diffuse erythema over the anterior chest wall and marked leukocytosis developed after coronary artery bypass grafting. This prompted débridement and opening of the sternotomy wound. The cause of the erythema was pyoderma gangrenosum that expressed the pathergy phenomenon. The pyoderma gangrenosum subsequently involved the saphenous vein harvest site, a chest-tube site, and a previously healed abdominal scar. The patient died when an exposed saphenous vein graft was perforated. To our knowledge, this is the 9th reported case of pathergy due to pyoderma gangrenosum after coronary artery bypass grafting and the first with a fatal outcome.

  6. Pyoderma gangrenosum after trauma in a dog

    PubMed Central

    NAGATA, Noriyuki; YUKI, Masashi; ASAHINA, Ryota; SAKAI, Hiroki; MAEDA, Sadatoshi

    2016-01-01

    A 12-year-old male entire Miniature Pinscher presented with excoriations at various body sites, progressively forming ulcers and enlarging until arrested by treatment. Based on the clinical presentation and histopathological analyses, sterile neutrophilic dermatosis was suspected. Therefore, the dog was started on prednisolone. Marked improvement was achieved with prednisolone treatment, suggesting a diagnosis of pyoderma gangrenosum (PG). Transcription levels of cytokine mRNA in lesional skin before and after treatment from this dog were quantified by real-time RT-PCR. Transcription levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-8 and IL-17A were higher in lesional skin before treatment than after treatment. Levels of various cytokines could be increased in lesional skin of dogs with PG as well as in human patients with PG. PMID:27108868

  7. Diagnosis and management of parastomal pyoderma gangrenosum

    PubMed Central

    Wu, Xian-rui; Shen, Bo

    2013-01-01

    Parastomal pyoderma gangrenosum (PPG) is an unusual neutrophilic dermatosis characterized by painful, necrotic ulcerations occurring in the area surrounding an abdominal stoma. It typically affects young to middle-aged adults, with a slight female predominance. The underlying etiology for PPG remains enigmatic but aberrant immune response to injury may play a pivotal role. The reported risk factors for the development of PPG include the presence of extra-intestinal manifestations, autoimmune disorders and obesity, along with local factors, such as the presence of parastomal hernia or pressure ulcer. PPG can develop at any time after the stoma construction. The histopathological features of PPG are not pathognomonic and its diagnosis is mainly based on clinical features. The management of PPG often requires a multidisciplinary approach, with a combination of local wound care and systemic medications. PMID:24759661

  8. Successful Treatment of Pyoderma Gangrenosum with Cryoglobulinemia and Hepatitis C

    PubMed Central

    Pourmorteza, Mohsen; Tawadros, Fady; Bader, Gilbert; Al-Tarawneh, Mohammad; Cook, Emilie; Shams, Wael; Young, Mark

    2016-01-01

    Patient: Male, 68 Final Diagnosis: Pyoderma gangrenosum Symptoms: Worsening lower extremity wound Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Pyoderma gangrenosum is a rare, ulcerative cutaneous condition that was first described by Brocq in 1916. This diagnosis is quite challenging as the histopathological findings are nonspecific. Pyoderma gangrenosum is usually associated with inflammatory bowel disease, leukemia, and hepatitis C. We describe a rare clinical case of a patient with hepatitis C (HCV), mixed cryoglubinemia, and pyoderma gangrenosum, which was successfully treated with prednisone in combination with the new antiviral medication ledipasvir/sofosbuvir. Case Report: A 68-year-old male with a history of untreated HCV presented to the clinic with a left lower extremity ulcer that had progressively worsened over 4 days after the patient sustained a minor trauma to the left lower extremity. Examination revealed a 2×3 cm purulent ulcer with an erythematous rim on medial aspect of his left lower leg. HCV viral load and genotype analysis revealed genotype 1A with polymerase chain reaction (PCR) showing viral counts of 9,506,048 and cryoglobulinemia. With a worsening and enlarging erythematous ulcer and failure of IV antibiotic therapy, the patient underwent skin biopsy, which showed acanthotic epidermis with superficial and deep perivascular lymphoplasmacytic dermatitis admixed with mild neutrophilic infiltrate. The patient was subsequently started on ledipasvir/sofosbuvir and prednisone with a high suspicion of pyoderma gangrenosum. At one-month follow-up at the hepatology clinic, the patient demonstrated a near resolution of the lower extremity ulcer with undetectable viral load. Conclusions: Pyoderma gangrenosum is an inflammatory process of unknown etiology, and establishing the correct diagnosis can be a difficult task. For this reason it is prudent for clinicians to consider Pyoderma

  9. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra.

    PubMed

    Brenner, M; Ruzicka, T; Plewig, G; Thomas, P; Herzer, P

    2009-11-01

    The triad of sterile pyogenic arthritis, pyoderma gangrenosum and acne is known by the acronym of PAPA syndrome. It is a rare autosomal dominant disease of early onset. The treatment of pyoderma gangrenosum is challenging as there is often only partial response to systemic glucocorticosteroids and immunosuppressive therapies. We report the rapid and lasting response of pyoderma gangrenosum to the targeted treatment with the recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) anakinra in a patient with PAPA syndrome.

  10. [Pyoderma gangrenosum revealing colonic diverticulitis: Two cases].

    PubMed

    Fongue, J; Brajon, D; Visée, C; Combes, E; Andrac-Meyer, L; Berbis, P

    2015-11-01

    The association of pyoderma gangrenosum (PG) with colonic diverticulitis infection (DI) is relatively unknown. Herein, we describe two cases of PG with full recovery after colonic surgery. Case 1: an 83-year-old man presented with lesions on his legs that had been present for several weeks, and a diagnosis of PG was confirmed histologically. Abdominopelvic computed tomography (CT) performed on account of biological inflammatory syndrome revealed DI complicated by abscesses. Following the failure of two different antibiotic regimens, sigmoidectomy was performed. Postoperatively, the skin lesions healed without local or systemic corticosteroids. Case 2: a 63-year-old woman presented PG resistant to local and systemic corticosteroids and dapsone for several months. A particularly severe flare was accompanied by abdominal pain and inflammatory syndrome. CT revealed perforated sigmoid DI. Sigmoidectomy was performed after failure of drug therapy. The patient's PG subsequently improved and had disappeared without recurrence at 24months. Both of these cases of PG revealed DI. The hypothesis is that DI constituted a source of colonic inflammation, sending out bacterial antigenic stimuli that resulted in PG through deposition of circulating immune complexes. Removal of this inflammatory source appears to have enabled healing of PG. DI must be added to the list of systemic diseases associated with PG. In the case of isolated PG, CT may be used to detect asymptomatic DI. Early diagnosis could prevent serious gastrointestinal complications. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Surgical treatment of pyoderma gangrenosum following deep inferior epigastric perforator flap breast reconstruction.

    PubMed

    Tamer, Funda; Adışen, Esra; Tuncer, Serhan; Gurer, Mehmet A

    2016-09-01

    Pyoderma gangrenosum is a chronic inflammatory disease characterized by painful cutaneous ulcers. The etiology remains unknown; however, pyoderma gangrenousm can be triggered by surgery. Here we report the case of a 34-year-old Caucasian female that developed pyoderma gangrenosum following deep inferior epigastric perforator flap breast reconstruction. The patient was successfully treated with systemic immunosuppressive therapy and primary closure.

  12. Clofazimine in dermatitis ulcerosa (pyoderma gangrenosum). Open clinical trial.

    PubMed

    Mensing, H

    1988-01-01

    Five patients suffering from dermatitis ulcerosa (a variant of pyoderma gangrenosum) were treated with clofazimine in a daily dosage of 200 mg orally. Complete healing was noted in 2 patients, partial response in 2, no effect in 1. Side effects were mild and transitory in form of a red coloring of the skin (all patients) and mild ichthyosis (2 patients).

  13. Pyoderma gangrenosum affecting the eye, orbit, and adnexa. A review.

    PubMed

    McElnea, Elizabeth; Stephenson, Kirk; Fulcher, Tim

    2017-09-01

    While pyoderma gangrenosum (PG) most commonly affects the skin it can also involve other organs. It rarely affects the eye, orbit, or adnexa. Its early recognition and proper management with prompt initiation of immunosuppressive therapy are essential for the preservation of the eye and, in turn, vision, in these cases. Here, we review the limited literature already published regarding ocular involvement in PG.

  14. Pyoderma gangrenosum associated with cystic acne and hidradenitis suppurativa controlled by adding minocycline and sulfasalazine to the treatment regimen.

    PubMed

    Shenefelt, P D

    1996-05-01

    Pyoderma gangrenosum often presents a difficult therapeutic challenge. The case is described of a 42-year-old black man with the association of cystic acne, hidradenitis suppurativa, and seronegative arthritis with pyoderma gangrenosum. The pyoderma gangrenosum ulcers remained refractory to treatment until therapies aimed in part at the associated diseases were begun. Minocycline was given for treatment of cystic acne and hidradenitis suppurativa as well as pyoderma gangrenosum. Sulfasalazine was prescribed for seronegative arthritis as well as pyoderma gangrenosum. The combination therapy permitted healing of the pyoderma gangrenosum ulcers.

  15. Pyoderma Gangrenosum and Erythema Nodosum Revealing Takayasu's Arteritis

    PubMed Central

    Loetscher, Jonas; Fistarol, Susanna; Walker, Ulrich A.

    2016-01-01

    We report a Caucasian female who presented with simultaneous erythema nodosum and pyoderma gangrenosum due to underlying Takayasu's arteritis. Takayasu's arteritis is a chronic large vessel vasculitis of unknown cause. The disease has a worldwide distribution but is most commonly seen in Asian populations. There is a strong predilection for young females. The clinical presentation is variable, but mostly derives from stenosis or occlusion of affected arteries, resulting in claudication and ischemia. Skin manifestations are observed in up to 28% of patients with Takayasu's arteritis, with erythema nodosum reported more frequently in Caucasians. Pyoderma gangrenosum is more common in Asian patients. This report demonstrates the importance to exclude Takayasu's arteritis in patients with such skin lesions. PMID:28101023

  16. [Pyoderma gangrenosum--positive effect of cyclosporin A therapy ].

    PubMed

    Krauze, Ewa; Lis, Anna; Kamińska-Budzińska, Grazyna; Wygledowska-Kania, Mariola; Pierzchała, Ewa; Brzezińska-Wcisło, Ligia

    2002-10-01

    Although pyoderma gangrenosum is a disorder known since over 70 years, it still remains a diagnostic and therapeutic problem. We describe three subjects with pyoderma gangrenosum; two were females, one was male, one case was associated with colitis ulcerosa, two were without any related disorders. Histopathologic examinations supported the diagnosis in all cases. In spite of intensive topical and systemic treatment with corticosteroids, Dapsone, Clofazimine, no sufficient effects were achieved. Cyclosporin A introduced in the dose of 5 mg/kg/d resulted in dramatic response and complete remission. Serum CyA levels, biochemical parameters of liver and kidney function, blood pressure were monitored during the therapy. No adverse events due to Cyclosporin A were observed.

  17. Pyoderma gangrenosum mimicking mediastinitis after cardiac surgery: a case study.

    PubMed

    Hysi, I; Vincentelli, A

    2016-06-01

    Pyoderma gangrenosum is a dermatosis which associates both, necrosis and polynuclear infiltration of the skin. While the aetiology is not well understood, the disease is thought to be due to immune system dysfunction and it can occur after minor trauma or surgery. Although it has seldom been reported after cardiac surgery in the literature, it is not exceptional. Here we report a case of pyoderma gangrenosum after coronary artery bypass grafting in a 76-year-old patient with chronic idiopathic myelofibrosis. Diagnosis was clinically made and the patient was treated with systemic steroids. The lesions showed a remarkable improvement with this therapy. In the field of cardiac surgery, physicians of the surgical team and nurses should think about this diagnosis in all rapidly expanding postoperative lesions without improvement after debridement or antibiotics. The authors have no conflicts of interest to declare.

  18. [Pyoderma gangrenosum associated with rheumatoid arthritis: a case report].

    PubMed

    Beber, André Avelino Costa; Knob, Cristiane Faccin; Shons, Karen Regina Rosso; Neumaier, Walter; da Silva, João Carlos Nunes; Monticielo, Odirlei André

    2014-01-01

    Pyoderma gangrenosum is a chronic inflammatory dermatosis, which is associated with non-infectious systemic diseases such as rheumatoid arthritis and inflammatory bowel disease. It is more common in adults and may present with four distinct clinical forms, all leading to ulceration of the skin affected. Its diagnosis is clinical and demands exclusion of other causes. Treatment should be performed with local care and systemic therapy.

  19. Pyoderma Gangrenosum in a Patient with Hereditary Spherocytosis.

    PubMed

    Kwon, Hyoung Il; Paek, Jun Oh; Kim, Jeoung Eun; Ro, Young Suck; Ko, Joo Yeon

    2016-03-01

    Pyoderma gangrenosum (PG) is a rare, relapsing cutaneous disease with 4 distinctive clinical manifestations: ulcerative, bullous, pustular, and vegetative lesions. It mainly occurs in adults and is frequently associated with systemic diseases, most commonly inflammatory bowel disease, rheumatologic disease, or hematological dyscrasias. However, there have been no previous reports of PG in a patient with hereditary spherocytosis, a common inherited hemolytic anemia. We report here a unique case of PG in a 15-year-old boy with underlying hereditary spherocytosis.

  20. [Pyoderma gangrenosum: report of three cases in plastic surgery].

    PubMed

    Eulufí M, Alex; Calderón O, Wilfredo; Piñeros B, José Luis; Silva C, Macarena; Cuadra C, Alvaro; Léniz M, Patricio; Gómez S, Lyonel; Eulufí M, Christian; Calderón M, Daniel

    2006-03-01

    Pyoderma Gangrenosum is a rare disease whose etiology is probably autoimmune. We report two males aged 48 and 49 years and one female aged 54 years, with lesions in the right thigh, right leg and in the borders of a surgical incision in the chest. This article gives a brief description of the lesions, tips for diagnosis and help for the initial management and treatment.

  1. Genital pyoderma gangrenosum: report of two cases and published work review of Japanese cases.

    PubMed

    Satoh, Masataka; Yamamoto, Toshiyuki

    2013-10-01

    Pyoderma gangrenosum is an ulcerative skin disorder showing characteristic non-infectious ulcers and affects the lower extremities in approximately 70% of cases. Pyoderma gangrenosum is commonly associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Herein, we report two cases of Japanese patients diagnosed with genital pyoderma gangrenosum. Case 1 was a 74-year-old woman without associated systemic complications, whose skin lesion resembled a squamous cell carcinoma and was limited to the vulva. Case 2 is an 89-year-old man, who suffered from myelodysplastic syndrome and acute myeloid leukemia, and presented with penile and leg ulcers mimicking pressure sores. Both cases responded well to systemic steroids. We review 13 genital pyoderma gangrenosum cases (76.9% male; aged 30-89 years) from 1996 to 2012 in Japan, including 11 previously reported cases and the present study's two cases. Four of the 13 genital pyoderma gangrenosum cases had associated systemic diseases and their skin lesions spread to the extragenital areas. Eight of the remaining nine genitalia-localized pyoderma gangrenosum cases had no associated systemic diseases. In conclusion, genital pyoderma gangrenosum is rare and may be misdiagnosed. It should therefore be considered in cases of refractory genital ulcers. In addition, genitalia-localized pyoderma gangrenosum tends to be without systemic complications.

  2. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum

    PubMed Central

    Saha, Maitrayee; Jain, Bhawna Bhutoria; Chattopadhyay, Sarbani; Podder, Indrashis

    2016-01-01

    Mycosis fungoides (MF), a primary cutaneous T-cell lymphoma, accounts for <1% of non-Hodgkin lymphomas. The diagnosis of classic MF is based on a constellation of typical clinical presentation, histopathology, immunohistochemistry, and T-cell monoclonality detected by molecular studies. Rarely, atypical clinical presentation may occur. The typical immunohistochemical phenotype is, CD2 +ve, CD3 +ve, CD5 +ve, CD4 +ve, and CD8 − ve. Here, we report a rare case of CD8 +ve MF in a 43-year-male patient who was clinically diagnosed as pyoderma gangrenosum initially. The atypical presentation and rarity of such case have prompted this report. PMID:27688458

  3. A case of pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and treated by autograft.

    PubMed

    Vereecken, P; Wautrecht, J C; De Dobbeleer, G; Heenen, M

    1997-01-01

    Pyoderma gangrenosum is a chronic inflammatory ulcerative skin disease of unknown etiology, often associated with various systemic disorders such as inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, diabetes mellitus and hematologic malignancies. The ulcers are characterized by their undermined violaceous borders. The disease remains a therapeutic challenge. Corticosteroids are the mainstay of therapy; however, side effects from this treatment and recalcitrant pyoderma gangrenosum require therapeutic alternatives. We report the case of a large subacute pyoderma gangrenosum stabilized with lymecycline, topical benzoyl peroxide and successfully treated by an autograft. This observation supports the opinion that the risk of pathergy of a graft can be avoided by the stabilization of the disease.

  4. Pediatric pyoderma gangrenosum: a systematic review and update.

    PubMed

    Kechichian, Elio; Haber, Roger; Mourad, Nadim; El Khoury, Rana; Jabbour, Samer; Tomb, Roland

    2017-02-23

    Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as there are many newly reported associated diseases and drugs. This paper aims to review all recent available data on pediatric PG. A systematic review of the literature was conducted using Embase, Medline, and Cochrane databases. A total of 132 articles were included in the review. The most commonly reported underlying diseases in pediatric PG are inflammatory bowel diseases followed by hematologic disorders, vasculitis, immune deficiencies and Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome. More than half of the cases occur with no underlying disease. The most frequently reported clinical presentation is multiple disseminated ulcers. Treatment should be tailored according to the underlying etiology. It includes systemic steroids, corticosteroid sparing agents such as dapsone and cyclosporine, and TNF-alpha inhibitors such as adalimumab and infliximab. Response to treatment is high with cure rates reaching 90%. A high index of suspicion and a thorough workup are mandatory in the management of pediatric PG.

  5. Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome.

    PubMed

    Stichweh, Dorothee S; Punaro, Marilynn; Pascual, Virginia

    2005-01-01

    Infliximab, a chimeric antitumor necrosis factor alpha monoclonal antibody (anti-TNF alpha), has been recently shown to have a beneficial effect on pyoderma gangrenosum associated with inflammatory bowel disease. Patients with the syndromic triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne, an autoinflammatory process caused by mutations in the CD2 binding protein-1 (CD2BP1) gene, can have severe pyoderma gangrenosum. We describe a 14-year-old patient with this syndrome who was unresponsive to multiple therapies. A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome.

  6. Pyoderma Gangrenosum: A Commonly Overlooked Ulcerative Condition

    PubMed Central

    Tay, Daniel Zunsheng; Tan, Ki-Wei; Tay, Yong-Kwang

    2014-01-01

    Background: Pyoderma ga ngrenosum (PG) is a rare, inflammatory, destructive neutrophilic dermatosis, which mimics other ulcerative conditions. Materials and Methods: In a retrospective study based on patients diagnosed with PG over a 3-year period (2010–2013), we evaluated demographics, anatomical sites, number of lesions, subtypes, histopathology, associated conditions, treatment regimens, healing time, and recurrence. Results: Of our five patients, there were three males and two females, age ranging between 19 and 58 years (mean age 38 years). Four had single lesions localized to the lower limbs while one had multiple lesions (more than five) over bilateral hands and legs. Ulcerative subtype was observed in all the patients. One exhibited pathergy. Skin biopsies were done in four patients, revealing dense neutrophilic infiltrates in three cases and leukocytoclastic vasculitis in one. Associated systemic diseases were observed in all patients, four having inflammatory bowel disease and one having both systemic lupus erythematosus and anti-phospholipid syndrome. The patients were all treated with systemic corticosteroids either alone or in combination with immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus), and wound dressing. Split-thickness skin graft was done in one patient. Complete healing was achieved in all patients, ranging from one to 3 months after diagnosis. No recurrence was reported. Conclusions: Systemic corticosteroids, either alone or in combination with steroid-sparing agents are the mainstay of treatment. Should family physicians encounter a rapidly progressing ulcer that has poor response to usual wound management, timely referral to dermatology should be made. PMID:25657946

  7. Pyoderma gangrenosum: a commonly overlooked ulcerative condition.

    PubMed

    Tay, Daniel Zunsheng; Tan, Ki-Wei; Tay, Yong-Kwang

    2014-01-01

    Pyoderma ga ngrenosum (PG) is a rare, inflammatory, destructive neutrophilic dermatosis, which mimics other ulcerative conditions. In a retrospective study based on patients diagnosed with PG over a 3-year period (2010-2013), we evaluated demographics, anatomical sites, number of lesions, subtypes, histopathology, associated conditions, treatment regimens, healing time, and recurrence. Of our five patients, there were three males and two females, age ranging between 19 and 58 years (mean age 38 years). Four had single lesions localized to the lower limbs while one had multiple lesions (more than five) over bilateral hands and legs. Ulcerative subtype was observed in all the patients. One exhibited pathergy. Skin biopsies were done in four patients, revealing dense neutrophilic infiltrates in three cases and leukocytoclastic vasculitis in one. Associated systemic diseases were observed in all patients, four having inflammatory bowel disease and one having both systemic lupus erythematosus and anti-phospholipid syndrome. The patients were all treated with systemic corticosteroids either alone or in combination with immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus), and wound dressing. Split-thickness skin graft was done in one patient. Complete healing was achieved in all patients, ranging from one to 3 months after diagnosis. No recurrence was reported. Systemic corticosteroids, either alone or in combination with steroid-sparing agents are the mainstay of treatment. Should family physicians encounter a rapidly progressing ulcer that has poor response to usual wound management, timely referral to dermatology should be made.

  8. [Pyoderma gangrenosum after intramedullary nailing of tibial shaft fracture: A differential diagnosis to necrotizing fasciitis].

    PubMed

    Hackl, S; Merkel, P; Hungerer, S; Friederichs, J; Müller, N; Militz, M; Bühren, V

    2015-12-01

    Pyoderma gangrenosum is a rare non-infectious neutrophilic dermatitis, whereas necrotizing fasciitis is a life-threatening bacterial soft tissue infection of the fascia and adjacent skin. As in the case described here after intramedullary nailing, the clinical appearance of both diseases can be similar. Because of the completely different therapeutic approach and a worse outcome in the case of false diagnosis, pyoderma gangrenosum should always be taken into consideration before treating necrotizing fasciitis.

  9. Postsurgical Pyoderma Gangrenosum Following Carpal Tunnel Release: A Rare Disease Following a Common Surgery

    PubMed Central

    Mendenhall, Shaun D.; Neumeister, Michael W.; Berry, Nada N.

    2017-01-01

    Objective: Postsurgical pyoderma gangrenosum is a rare but potentially devastating condition for surgical patients. While pyoderma gangrenosum has 2 subtypes, typical and atypical, each can be further classified by its heralding features. These include ulcerative, pustular, bullous, and vegetative. The presentation can be a result of trauma or, as mentioned before, postsurgical. The plastic and reconstructive surgeon most likely will encounter postsurgical pyoderma gangrenosum in practice, as it has been reported in patient populations frequently seen in plastic surgery clinics. Methods: We present a unique case of idiopathic postsurgical pyoderma gangrenosum in a patient who presented after carpal tunnel release, the most common surgery of the hand and wrist performed in the United States annually. This is believed to be the first ever case reported in the literature of pyoderma gangrenosum following carpal tunnel release. Results: The patient's disease course was complicated by surgical debridement prior to diagnosis. Unfortunately, this condition necessitated mid-forearm amputation. The wound eventually healed with primary closure and appropriate medical therapy. Conclusion: Previous experience with this disease, a high index of suspicion, and general education regarding the disease process and its management could potentially have prevented this outcome. We hope to underscore that it is important to consider a patient's entire history and to have a high index of suspicion in unusual postsurgical wounds in order to adequately diagnose, treat, and manage patients who develop postsurgical pyoderma gangrenosum.

  10. Pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis: efficacy of anti-tumor necrosis factor α therapy.

    PubMed

    Bruzzese, Vincenzo

    2012-12-01

    We report the case of a patient with a simultaneous presence of pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis. This condition differs from both the PASH (pyoderma gangrenosum, acne, and suppurative hidradenitis) syndrome, in which arthritis is absent, and the PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome, in which suppurative hidradenitis is lacking. Our patient failed to respond to etanercept therapy, whereas all dermatologic and rheumatic manifestations completely regressed following infliximab infusion. We therefore propose that simultaneous presence of pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and seronegative spondyloarthritis might represent a distinct syndrome that could be termed the PASS syndrome. Tumor necrosis factor α therapies seem to play selective roles.

  11. Pyoderma gangrenosum in a six-month-old boy.

    PubMed

    Koturoğlu, Güldane; Vardar, Fadil; Ozkinay, Ferda; Kurugöl, Zafer; Akalin, Taner; Ozkinay, Cihangir

    2006-01-01

    Pyoderma gangrenosum (PG) is an uncommon, chronic ulcerative condition of the skin that was first described in 1930. It can occur in any age group, but only 4% of the patients are infants or children. An underlying systemic disease is present in approximately 50% of the patients with PG. The most common associations include inflammatory bowel disease, arthritis, lymphoproliferative disorders and chronic recurrent multifocal osteomyelitis (CRMO). PG has been reported in association with CRMO in only a few children whose ages were between 18 months and 12 years. We report a six-month-old boy who was diagnosed as CRMO based on his clinical examination and histological findings. This is the youngest case reported in the literature (under 12 months of age) with PG associated with CRMO.

  12. Exuberant pyoderma gangrenosum in a patient with autoimmune hepatitis*

    PubMed Central

    Dantas, Stephanie Galiza; Quintella, Leonardo Pereira; Fernandes, Nurimar Conceição

    2017-01-01

    Pyoderma gangrenosum is a rare neutrophilic dermatosis, which usually presents as ulcers with erythematous-violaceous undermined edges and a rough base with purulent or sanguinous exudate. It can be primary or associated with an underlying disease. However, rare cases of its association with autoimmune hepatitis have been described in the literature. Diagnosis is based on a characteristic clinical picture and ruling out other causes of ulcers. This paper aims to discuss the management of corticosteroid therapy and the importance of local treatment. We report a case with torpid evolution, presented with multiple and deep ulcers in a young patient with autoimmune hepatitis, causing pain and significant disability. We observed complete healing of lesions after two months of successful treatment. PMID:28225969

  13. Pyoderma gangrenosum with wrist joint destruction: case report.

    PubMed

    Choe, Hyonmin; Sakano, Hiroaki; Takigami, Hidetake; Inaba, Yutaka; Matsuo, Kosuke; Saito, Tomoyuki

    2013-02-01

    Pyoderma gangrenosum (PG) is a rare, noninfectious, neurotrophic dermatosis. We observed a case of PG mimicking cutaneous and osteoarticular infections that presented with a prolonged ulcer on the forearm, severe wrist pain, anemia, substantial local and systemic inflammation as evaluated by serum laboratory data, and carpal osteolysis. Although PG rarely damages joints, the ulcer extended to the joint and destroyed the osteochondral tissues. Advanced ulcerative colitis, which is a most common comorbidity of PG, proved to be an underlying disease. Antibiotic and surgical treatment did not heal the ulcer, which was successfully treated with corticosteroids. This intractable ulcer is often misdiagnosed. Hence when a patient presents with an enlarged, painful, unusual skin lesion, PG should always be considered.

  14. Biologics for the treatment of pyoderma gangrenosum in ulcerative colitis

    PubMed Central

    Arivarasan, K; Bhardwaj, Vaishali; Sud, Sukrit; Sachdeva, Sanjeev

    2016-01-01

    Pyoderma gangrenosum (PG) is an uncommon extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite limited published literature, biologics have caused a paradigm shift in the management of this difficult-to-treat skin condition. The clinical data and outcomes of three patients with active ulcerative colitis and concurrent PG treated with biologics (infliximab two and adalimumab one) are reviewed in this report. Biologics were added because of the sub-optimal response of the colonic symptoms and skin lesions to parenteral hydrocortisone therapy. All three patients showed a dramatic response to the addition of the biologics. In view of the rapid healing of the skin lesions, superior response rate, and the additional benefit of improvement in the underlying colonic disease following treatment, anti-tumor necrosis factor blockers should be considered as a first line therapy in the management of PG with underlying IBD. PMID:27799888

  15. Pyoderma gangrenosum with increased levels of serum cytokines.

    PubMed

    Kozono, Kana; Nakahara, Takeshi; Kikuchi, Satoko; Itoh, Eriko; Kido-Nakahara, Makiko; Furue, Masutaka

    2015-12-01

    A 66-year-old woman presented after an episode of accidental trauma with a painful ulcer on her scalp which rapidly enlarged in size, accompanied by central necrosis and undermining ulceration. The patient's past history was negative for underlying systemic disease, although she had had a similar post-traumatic intractable leg ulcer 3 years prior, which was unresponsive to surgical management but successfully treated with systemic steroids. A biopsied specimen from the scalp showed marked neutrophilic infiltrates in the dermis, compatible with a diagnosis of pyoderma gangrenosum (PG). The large ulcerative lesion responded very well to oral steroid therapy, showing rapid epithelialization. Serum levels of granulocyte colony-stimulating factor and interleukin-6 were significantly elevated prior to treatment, with decrease to normal levels after treatment. Serum tumor necrosis factor (TNF)-α and granulocyte macrophage colony-stimulating factor levels were within normal limits. The significance and pathogenic role of cytokine burst in PG is reviewed and discussed.

  16. Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation.

    PubMed

    Marzano, A V; Borghi, A; Meroni, P L; Cugno, M

    2016-11-01

    Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1β to its active isoform IL-1β. The overproduction of IL-1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.

  17. 'Sticky' neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.

    PubMed Central

    Dwarakanath, A D; Yu, L G; Brookes, C; Pryce, D; Rhodes, J M

    1995-01-01

    Pyoderma gangrenosum is strongly associated with inflammatory bowel disease and exhibits pathergy, occurring at sites of previous minor trauma. A patient is presented with a 21 year history of extensive ulcerative colitis, who developed pyoderma gangrenosum and arthralgia while receiving high dose corticosteroids for active ulcerative colitis. The arthralgia exhibited pathergy affecting particularly the left temporomandibular joint, which was stressed by an asymmetric bite, and the left elbow, which had been fractured many years previously. This prompted the hypothesis that neutrophils in this condition may be marginated, as a result of increased stickiness of either the neutrophil or the vascular endothelium. The introduction of heparin therapy was associated with rapid resolution of the arthralgia, pyoderma gangrenosum, and ulcerative colitis. Images Figure 1 Figure 3 PMID:7489951

  18. Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment.

    PubMed

    Alavi, Afsaneh; French, Lars E; Davis, Mark D; Brassard, Alain; Kirsner, Robert S

    2017-02-21

    Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the genetic basis of PG and the role of auto-inflammation provides a better understanding of the disease and new therapeutic targets. PG equally affects patients of both sexes and of any age. Uncontrolled cutaneous neutrophilic inflammation is the cornerstone in a genetically predisposed individual. Multimodality management is often required to reduce inflammation, optimize wound healing, and treat underlying disease. A gold standard for the management of PG does not exist and high-level evidence is limited. Multiple factors must be taken into account when deciding on the optimum treatment for individual patients: location, number and size of lesion/ulceration(s), extracutaneous involvement, presence of associated disease, cost, and side effects of treatment, as well as patient comorbidities and preferences. Refractory and rapidly progressive cases require early initiation of systemic therapy. Newer targeted therapies represent a promising pathway for the management of PG, and the main focus of this review is the management and evidence supporting the role of new targeted therapies in PG.

  19. Postoperative Pyoderma Gangrenosum Following Video-Assisted Thoracic Surgery.

    PubMed

    Tolkachjov, Stanislav N; Sun, Philip Y; Bridges, Alina G

    2017-07-01

    Pyoderma gangrenosum (PG) is a neutrophilic, ulcerative dermatosis that can develop at sites of cutaneous trauma, including surgical incisions, a phenomenon known as pathergy. The characteristic lesion is a painful, rapidly expanding ulceration with a violaceous undermined border.1 A biopsy taken from the expanding violaceous border shows predominantly neutrophilic dermal inflammation with neutrophilic abscess formation.

    The etiology of PG appears to be variable among patients, as about a half of the reported cases are associated with systemic disease such as inflammatory bowel disease, rheumatoid arthritis, or myeloproliferative disorders, while the other half seem to be idiopathic.2 PG is difficult to diagnose as other etiologies, including infectious, vasculitic, and other inflammatory dermatoses, must be excluded.1 Histopathologic and biochemical markers of PG, such as dermal neutrophilic infiltrate or overexpression of interleukin-8,3 respectively, are not pathognomonic. Given that several drugs, such as hydralazine, mesalamine, and sunitinib, are reportedly associated with PG, failure to recognize this association and stop these medications may delay diagnosis and therapy. We report a case of idiopathic postoperative PG following video-assisted thoracic surgery (VATS).

    J Drugs Dermatol. 2017;16(7):711-713.

    .

  20. Pyoderma gangrenosum: an exceptional complication of venous access device.

    PubMed

    La Marca, Sophie; Toussoun, Gilles; Ho Quoc, Christophe; Sebban, Henry; Delay, Emmanuel

    2014-01-01

    Pyoderma gangrenosum (PG) is a rare disease whose precise etiology remains unknown. It causes rapidly developing skin necrosis and can occur after surgery, or after a nonspecific external stimulus. This condition is difficult to diagnose because it often mimics a fulminant infection. We present a case of very significant local presentation of PG after placement of a venous access device. Fifteen days after placement, the patient developed extensive cutaneous ulcers and necrosis in the subclavicular area, which led to the misdiagnosis of infection. The device was removed and the patient was given antibiotics. Because there was no improvement following antibiotic treatment, combined with the worrying and extensive appearance of the skin and extremely intense pain, the diagnosis of PG was made. The patient was immediately treated with high-dose corticosteroids, resulting in rapid improvement of the lesions and relief of pain. PG should be considered in cases of extensive, antibiotic-resistant ulceration and treatment with corticosteroids should be initiated. Clinical improvement is usually dramatic, with almost immediate suppression of the pain and arrest of the lesion's progression. Early treatment is the best guarantee for an effective recovery.

  1. Risk of Developing Pyoderma Gangrenosum after Procedures in Patients with a Known History of Pyoderma Gangrenosum - A Retrospective Analysis.

    PubMed

    Xia, Fan Di; Liu, Kristina; Lockwood, Stephen; Butler, Daniel; Tsiaras, William G; Joyce, Cara; Mostaghimi, Arash

    2017-09-22

    The risk of postoperative pyoderma gangrenosum (PG) in patients with a known history of PG is unknown. To quantify risk and identify patient/procedure-related risk factors for postsurgical PG recurrence/exacerbation in patients with known history of PG. We retrospectively evaluated the likelihood of postsurgical PG recurrence/exacerbation for all patients with a confirmed diagnosis of PG at Brigham & Women's Hospital and Massachusetts General Hospital from 2000-2015. 5.5% (n=33) of procedures led to recurrence of PG in 15.1% (n=25) of patients. Compared to skin biopsy, small open surgeries had an adjusted odds ratio (aOR) of 8.65 (1.55, 48.33) for PG recurrence/exacerbation; large open surgeries had an aOR of 5.97 (1.70, 21.00); and Mohs surgery/skin excision had an aOR of 6.47 (1.77, 23.61). PG chronically present at the time of procedure had an aOR of 4.58 (1.72, 12.22). Immunosuppression, time elapsed since original PG diagnosis, and procedure location did not significantly influence risk. Our study is limited by its retrospective nature and relatively small sample size. There is a small but clinically meaningful risk of postsurgical PG recurrence/exacerbation in patients with known history of PG; higher risks occur with more invasive procedures and chronically present PG. Copyright © 2017. Published by Elsevier Inc.

  2. Eradication of hepatitis C virus could improve immunological status and pyoderma gangrenosum-like lesions.

    PubMed

    Kondo, Yasuteru; Iwata, Tomoaki; Haga, Takahiro; Kimura, Osamu; Ninomiya, Masashi; Kakazu, Eiji; Kogure, Takayuki; Morosawa, Tatsuki; Aiba, Setsuya; Shimosegawa, Tooru

    2014-02-01

    Hepatitis C virus (HCV) can affect immune cells and induce various kinds of immune-related diseases including pyoderma gangrenosum. We experienced a difficult-to-treat case of pyoderma gangrenosum-like lesions in a patient with HCV infection. The patient was treated with pegylated interferon (PEG IFN)-α-2b and ribavirin (RBV) therapy and achieved a sustained virological response. Before the eradication of HCV, the frequency of T-helper 17 cells was remarkably high in comparison to chronic hepatitis C patients without extrahepatic immune-related diseases. Moreover, we could detect negative and positive strand-specific HCV RNA in the CD19(+) B lymphocytes and CD4(+) T lymphocytes. However, after the eradication of HCV, the immunological status became normal and the pyoderma gangrenosum-like lesions became stable without immunosuppressive therapy. Here, we report a sequential immunological analysis during PEG IFN/RBV therapy and the beneficial effect of HCV eradication in difficult-to-treat pyoderma gangrenosum-like lesions.

  3. A pregnancy-associated nonfamilial case of PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, acne) syndrome.

    PubMed

    Horiuchi, Isao; Fukatsu, Yuko; Ushijima, Junko; Nakamura, Eishin; Samajima, Koki; Kadowaki, Kanako; Takagi, Kenjiro

    2016-10-01

    Little is known about the influence of pregnancy on pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) syndrome. We experienced a rare case of pregnancy complicated with PAPA syndrome. The patient had various histories of skin and joint disorders and experienced subarachnoid hemorrhage during pregnancy; however, her skin lesion was unaffected.

  4. Pyoderma gangrenosum, acne, suppurative hidradenitis (PASH) and polycystic ovary syndrome: Coincidentally or aetiologically connected?

    PubMed

    Zivanovic, Dubravka; Masirevic, Iva; Ruzicka, Thomas; Braun-Falco, Markus; Nikolic, Milos

    2016-02-02

    The clinical triad of pyoderma gangrenosum, acne conglobata and hidradenitis suppurativa has been named PASH syndrome. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and inflammation. Hidradenitis suppurativa, like acne vulgaris, may be a feature of hyperandrogenism. Obesity may be associated with both hidradenitis suppurativa and PCOS. We describe a possible association between PASH syndrome and PCOS.

  5. Rare association of pyoderma gangrenosum and palmoplantar pustulosis: a case report and review of the previous works.

    PubMed

    Ohtsuka, Mikio; Yamamoto, Toshiyuki

    2014-08-01

    Pyoderma gangrenosum is a rare inflammatory, ulcerative skin disease that mainly involves the lower extremities. It frequently occurs in association with systemic diseases such as inflammatory bowel disease, myeloproliferative disorders and rheumatoid arthritis. Palmoplantar pustulosis is also an inflammatory dermatosis characterized by recurrent sterile pustules localized on the palms and soles. These two dermatoses are histologically characterized by neutrophilic infiltration into the lesional skin. Co-occurrence of pyoderma gangrenosum and palmoplantar pustulosis in a single patient is extremely rare. We report a case of pyoderma gangrenosum occurred in a patient with palmoplantar pustulosis, with a review of the previously reported cases. A 68-year-old Japanese woman with a 10-year history of palmoplantar pustulosis developed a skin ulcer on the left lower leg. The ulcer was diagnosed as pyoderma gangrenosum based on the clinical and histological findings, and rapidly improved in response to oral prednisolone. In addition to our case, five cases with palmoplantar pustulosis who developed pyoderma gangrenosum have been reported. These cases were thought to have some characteristics in common, such as marked female predominance, no association with inflammatory bowel disease and myeloproliferative disorders, and good response to less aggressive therapy. The co-occurrence of pyoderma gangrenosum and palmoplantar pustulosis in our case may have an etiological link, rather than being a coincidental complication.

  6. Pyoderma gangrenosum outside the context of inflammatory bowel disease treated successfully with infliximab.

    PubMed

    Swale, V J; Saha, M; Kapur, N; Hoffbrand, A V; Rustin, M H A

    2005-03-01

    A 63-year-old man with chronic lymphocytic leukaemia developed pyoderma gangrenosum following minor trauma to the leg. He required intensive inpatient management with a multitude of treatments including larval therapy, surgical debridement, ciclosporin, methotrexate, thalidomide, pulsed intravenous methylprednisolone and high-dose intravenous immunoglobulin, clofazamine and high dose oral corticosteroids, none of which were helpful. Treatment complications included steroid-induced diabetes, Cushing's syndrome and perforated peptic ulcer. The pyoderma remained refractory to treatment and continued to extend until he received intravenous infliximab 5 mg/kg at weeks 0, 2 and 6.

  7. Chronic recurrent multifocal osteomyelitis preceding pyoderma gangrenosum and occult ulcerative colitis in a pediatric patient.

    PubMed

    Omidi, C J; Siegfried, E C

    1998-01-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is a clinicopathologic entity of unknown origin mainly affecting children and young adults. It shares many clinical features with pyoderma gangrenosum (PG), an uncommon ulcerating inflammatory disorder of the dermis and underlying subcutaneous fat. Both conditions are chronic and relapsing, and have been associated with inflammatory bowel disease (IBD). The diagnoses are made by exclusion. Histology is nonspecific and cultures are negative. There has been only one previous report of both conditions occurring in the same patient. Here we describe the second case, a 12-year-old girl who developed pyoderma gangrenosum in direct continuity to an underlying CRMO lesion of the right anterior tibia. Occult ulcerative colitis (UC) was subsequently discovered.

  8. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q.

    PubMed

    Yeon, H B; Lindor, N M; Seidman, J G; Seidman, C E

    2000-04-01

    Pyoderma gangrenosum, cystic acne, and aseptic arthritis are clinically distinct disorders within the broad class of inflammatory diseases. Although this triad of symptoms is rarely observed in a single patient, a three-generation kindred with autosomal-dominant transmission of these three disorders has been reported as "PAPA syndrome" (MIM 604416). We report mapping of a disease locus for familial pyoderma gangrenosum-acne-arthritis to the long arm of chromosome 15 (maximum two-point LOD score, 5.83; recombination fraction [straight theta] 0 at locus D15S206). Under the assumption of complete penetrance, haplotype analysis of recombination events defined a disease interval of 10 cM, between D15S1023 and D15S979. Successful identification of a single disease locus for this syndrome suggests that these clinically distinct disorders may share a genetic etiology. These data further indicate the role of genes outside the major histocompatibility locus in inflammatory disease.

  9. Pulmonary manifestations of pyoderma gangrenosum: 2 cases and a review of the literature.

    PubMed

    Gade, Melina; Studstrup, Frej; Andersen, Anne Kathrine; Hilberg, Ole; Fogh, Carsten; Bendstrup, Elisabeth

    2015-04-01

    Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatologic disease that occasionally is accompanied by extracutaneous manifestations, amongst these is pulmonary involvement. The etiology is unknown. More than 50% of PG cases are associated with an underlying systemic disease such as inflammatory bowel disease, rheumatoid arthritis, hematological disorder or malignancy. Extracutaneous manifestations are rare and only 29 cases of pulmonary involvement have been reported previously in the literature. Pyoderma gangrenosum is usually diagnosed in the third to sixth decade, but early debut in childhood is also described. Skin manifestations are usually evident before pulmonary involvement, although primary lung affection is seen. Pulmonary involvement is diagnosed simultaneously or from a few weeks up to several years after the diagnosis of cutaneous PG. The most important differential diagnoses are lung cancer, lung abscess and Wegener's granulomatosis. Histological specimens will exclude these diagnoses. The treatment of PG is immune modulation, but due to the rarity of the disease, only one randomized treatment trials exists [1] and the long term course of PG with pulmonary involvement is unknown. We present two cases of pulmonary manifestations of pyoderma gangrenosum and a review of the literature.

  10. A novel de novo PSTPIP1 mutation in a boy with pyogenic arthritis, pyoderma gangrenosum, acne (PAPA) syndrome.

    PubMed

    Fathalla, Basil M; Al-Wahadneh, Adel M; Al-Mutawa, Mariam; Kambouris, Marios; El-Shanti, Hatem

    2014-01-01

    Autoinflammatory disorders are a group of Mendelian disorders characterized by seemingly unprovoked inflammatory bouts without high-titer autoantibodies or antigen-specific T-cells and are probably due to defects in the innate immunity. We here report on a 4-year-old Arabic boy with the clinical presentation of an autoinflammatory disorder, namely Pyogenic Arthritis, Pyoderma Gangrenosum and Acne (PAPA) syndrome. The presentation includes abscess formation after immunization and recurrent mono-articular acute arthritis in various joints that responded favourably to systemic glucocorticosteroids, albeit without acne or pyoderma gangrenosum. The mutation analysis of the boy identified a novel de novo mutation in PSTPIP1, the gene responsible for PAPA syndrome. We recommend that the diagnosis of PAPA syndrome should be entertained in the differential diagnosis of patients with recurrent sterile pyogenic arthritis prior to the development of pyoderma gangrenosum or acne in order to initiate a timely management of the disorder.

  11. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)--a new autoinflammatory syndrome distinct from PAPA syndrome.

    PubMed

    Braun-Falco, Markus; Kovnerystyy, Oleksandr; Lohse, Peter; Ruzicka, Thomas

    2012-03-01

    PAPA syndrome is a recently identified hereditary autoinflammatory syndrome clinically characterized by pyogenic arthritis, severe acne, and pyoderma gangrenosum. It is caused by mutations in the PSTPIP1 gene and may be closely linked to the aseptic abscesses syndrome, which has been shown to be associated with CCTG repeat amplification in the promoter region of PSTPIP1. We describe two unrelated patients with a clinical presentation quite similar to, yet distinct from, PAPA syndrome. Both patients had pyoderma gangrenosum and acute or remittent acne conglobata, but, in contrast to PAPA syndrome, lacked any episodes of pyogenic arthritis. Instead, they had suppurative hidradenitis. Mutations in PSTPIP1 exons 1 to 15 were excluded. In the promoter region, an increased repetition of the CCTG microsatellite motif was present on one allele in both patients. Alterations of the most commonly affected exons of the MEFV, NLRP3, and TNFRSF1A genes also were not detectable. One patient was treated with the interleukin (IL)-1 receptor antagonist anakinra and responded well, although without complete remission. This implies that IL-1ß may be of pathogenetic importance. Small number of patients, no gene mutation identified, and unclear efficacy of therapy are limitations. The clinical triad of pyoderma gangrenosum, acne, and suppurative hidradenitis represents a new disease entity within the spectrum of autoinflammatory syndromes, similar to PAPA and aseptic abscesses syndrome. For this disease, we propose the acronym "PASH" syndrome. PASH syndrome may respond to IL-1ß blockade. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  12. [A Case of Pyoderma Gangrenosum of the Penis Difficult to Distinguish from Fournier Gangrene].

    PubMed

    Taguchi, Makoto; Inoue, Takaaki; Nishida, Teruhisa; Kawabata, Takashi; Kawakita, Shigenari; Muguruma, Kouei; Murota, Takashi; Kinoshita, Hidefumi; Matsuda, Tadashi

    2015-11-01

    Here, we report a case of pyoderma gangrenosum of the penis which was difficult to distinguish from Fournier gangrene. The patient was a 54-year-old male who was aware of redness and swelling of the glanspenis for 1 month prior to a consultation at our department. Although he was diagnosed with herpes and treated at a nearby hospital, his symptoms did not improve. Subsequently, the patient visited our department following the onset of pain and fever. During his initial consultation, he had a fever of 39 °C as well as redness and swelling of the glans penis with partial spontaneous purulent discharge. His blood test revealed an elevated white blood cell count (20, 000/μl) and C-reactive protein (19.1 mg/dl). Because Fournier gangrene was suspected, administration of broad-spectrum antimicrobial agents was initiated but proved to be ineffective. An abscess (2 cm in diameter) was also noted in the umbilical region.Enterococcus faecalis was detected by the bacterial culture ; and therefore, Fournier gangrene was diagnosed. A partial penectomy was performed to control the infection. Pathological findings showed only non-specific inflammation ; however, fever persisted postoperatively and blood test results showed no improvement. Furthermore, new abscess lesions emerged on the right heel and back. Because the re-performed abscess bacterial culture test result was negative, pyoderma gangrenosum was suspected, and he was started on oral prednisolone (20 mg/day). On the following day, his fever subsided and his blood test results also showed improvement. A final diagnosis of pyoderma gangrenosum was ultimately made.

  13. A case of granulomatosis with polyangiitis and pyoderma gangrenosum successfully treated with infliximab and rituximab.

    PubMed

    Donmez, Salim; Pamuk, Omer N; Gedik, Mustafa; A K, Recep; Bulut, Gulay

    2014-05-01

    Here, we present a young male patient who was admitted with alveolar hemorrhage, arthritis and cutaneous lesions, who later developed bilateral orbital involvement and pyoderma gangrenosum (PG). He also had pathergy test positivity. The patient was refractory to conventional immunosuppressive therapy. Therefore, multiple devastating PG lesions and disease activity in granulomatosis with polyangiitis (GPA) were controlled with infliximab. Later, rituximab was used with success to prevent recurrence of symptoms. The relationship of PG with various autoimmune diseases is known; however, PG in GPA has been only rarely reported. Biologic agents might prove to be effective in GPA and PG patients who are refractory to standard immunosuppressive therapy.

  14. Pseudoepitheliomatous hyperplasia and pyoderma gangrenosum after a brown recluse spider bite.

    PubMed

    Hoover, E L; Williams, W; Koger, L; Murthy, R; Parsh, S; Weaver, W L

    1990-02-01

    Brown recluse spider bites may result in extensive soft tissue injury, causing months of disability. We have described a patient who had a series of extensive surgical debridements after envenomation. Despite skin grafting, persistent cutaneous lesions and extensive satellitosis progressed to involve the entire lower extremity. A recent biopsy showed pseudoepitheliomatous hyperplasia and pyoderma gangrenosum complicating the original injury. Although the role of early surgical excision and newer forms of medical treatment including dapsone and antivenom are still in evolution, recent reports suggest that the majority of patients will respond to medical therapy and may not require any surgical intervention.

  15. Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome Maps to Chromosome 15q

    PubMed Central

    Yeon, Howard B.; Lindor, Noralane M.; Seidman, J. G.; Seidman, Christine E.

    2000-01-01

    Pyoderma gangrenosum, cystic acne, and aseptic arthritis are clinically distinct disorders within the broad class of inflammatory diseases. Although this triad of symptoms is rarely observed in a single patient, a three-generation kindred with autosomal-dominant transmission of these three disorders has been reported as “PAPA syndrome” (MIM 604416). We report mapping of a disease locus for familial pyoderma gangrenosum–acne–arthritis to the long arm of chromosome 15 (maximum two-point LOD score, 5.83; recombination fraction [θ] 0 at locus D15S206). Under the assumption of complete penetrance, haplotype analysis of recombination events defined a disease interval of 10 cM, between D15S1023 and D15S979. Successful identification of a single disease locus for this syndrome suggests that these clinically distinct disorders may share a genetic etiology. These data further indicate the role of genes outside the major histocompatibility locus in inflammatory disease. PMID:10729114

  16. Intravenous Immunoglobulin as Salvage Therapy in Refractory Pyoderma Gangrenosum: Report of a Case and Review of the Literature

    PubMed Central

    Cafardi, John; Sami, Naveed

    2014-01-01

    Pyoderma gangrenosum is a neutrophilic dermatosis that occurs both as a primary disorder as well as secondary to an underlying disease. Due to its low prevalence there are limited data on therapeutics, particularly in refractory cases. Here, we discuss a case successfully managed with intravenous immunoglobulin and review the supporting literature. PMID:25493078

  17. Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the treatment of Pyoderma gangrenosum associated with Crohn's disease.

    PubMed

    Zaccagna, Alessandro; Bertone, Alberto; Puiatti, Paolo; Picciotto, Franco; Sprujevnik, Tatiana; Santucci, Renato; Rossini, Francesco Paolo

    2003-01-01

    Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's disease successfully treated with infliximab. The efficacy of this drug in many inflammatory diseases has already been reported, but its use in PG has only been seen in very few cases. Our study confirms that this therapy is a valid alternative solution for treating PG, which is often unresponsive to conventional therapies.

  18. Pyoderma gangrenosum in a patient with chronic granulomatous disease: A case report.

    PubMed

    Nanoudis, Sideris; Tsona, Afroditi; Tsachouridou, Olga; Morfesis, Petros; Loli, Georgia; Georgiou, Adamantini; Zebekakis, Pantelis; Metallidis, Symeon

    2017-08-01

    The simultaneous occurrence of pyoderma gangrenosum (PG) and chronic granulomatous disease (CGD) is uncommon and few cases have been reported worldwide. PG is a rare, chronic, ulcerative, neutrophilic skin disease of unknown etiology that requires immunosuppressive treatment. CGD belongs to Primary Immune Deficiencies in which the main defect lies in an inability of the phagocytic cells to generate superoxide making patients susceptible to serious, potentially life-threatening bacterial and fungal infections. In this manuscript, we present a case of ulcerative pyoderma gangrenosum in a 28-year-old man with recent diagnosis of chronic granulomatous disease during hospitalization for resistant pulmonary tuberculosis complicated with Aspergillus infection. Second-line therapy with dapsone and intravenous immunoglobulin was initially administered but eventually corticosteroids were added to treatment because of disease progression and further ulceration. Patient's ulcers were gradually healed with no side effects. Corticosteroids could be used under close monitoring for the treatment of PG in a patient with CGD, despite the increased risk for infections.

  19. [Pyoderma gangrenosum: spontaneous healing after early diagnosis. Three cases and general review].

    PubMed

    Viard, R; Scevola, A; Veber, M; Toussoun, G; Delay, E

    2013-04-01

    Pyoderma gangrenosum (PG) is a rare chronic inflammatory skin disease characterized by the recurring development of necrotizing and painful ulcers and therefore, often misinterpreted. This condition can simulate fulminant infection, particularly after surgery. The presentation is often impressive in extensive ulcerations and scarring and lead to significant sequelae. A rapid initial management avoids a dramatic evolution. We report the case of three PG for patients followed for breast reconstruction after breast cancer. PG is a neutrophilic dermatosis that can occur after injuries of varying intensity. Its shape after surgery is a rare disease whose presentation loud and fast pace "infectious" contrasts with the absence of inflammatory lymphangitis or lymphadenopathy. Be aware of prescribing high doses of corticosteroids. These three cases illustrate the importance for early diagnosis and treatment of PG, who can allow spontaneous healing without complex surgery, always feared in this context. Copyright © 2011. Published by Elsevier SAS.

  20. Pyoderma gangrenosum and systemic lupus erythematosus: a report of five cases and review of the literature.

    PubMed

    González-Moreno, J; Ruíz-Ruigomez, M; Callejas Rubio, J L; Ríos Fernández, R; Ortego Centeno, N

    2015-02-01

    Pyoderma gangrenosum (PG) is an uncommon, distinctive cutaneous ulceration which is usually idiopathic, but may be associated with many systemic disorders. The etiopathogenesis of PG is still not well understood. PG is part of the spectrum of the neutrophilic dermatoses and it has been proposed as a prototype of cutaneous autoinflammatory disease. PG usually has a good outcome under immunosuppressive treatment. Although PG has been associated with several systemic diseases, it has rarely been reported in association with systemic lupus erythematosus (SLE). In this article we report five cases of SLE-related PG and review the literature. Our findings support the possible relationship between active SLE and PG, although the mechanism remains unclear. Clinical manifestations, used treatments and outcomes of SLE-related PG do not differ from the described for the general population.

  1. The use of B vitamins for cutaneous ulcerations mimicking pyoderma gangrenosum in patients with MTHFR polymorphism.

    PubMed

    New, Douglas; Eaton, Philip; Knable, Al; Callen, Jeffrey P

    2011-04-01

    Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are associated with thrombophilia and vasculopathy that may result in cutaneous ulceration. Pyoderma gangrenosum (PG) is a clinical diagnosis that may be made following exclusion of alternate causes of ulceration, including vascular inflammatory or occlusive disease, infection, and malignant neoplasm. We describe 2 patients with MTHFR polymorphisms discovered during hypercoagulable evaluation for cutaneous ulcerations on the lower extremities. Both patients showed a rapid improvement following treatment with oral vitamin supplementation and local wound care. One patient developed several subsequent ulcers when he decided to discontinue his therapy, and following reinitiation of therapy, the new ulcerations healed. The treatment was tolerated well without any adverse effects. MTHFR polymorphisms should be part of a comprehensive laboratory evaluation during hypercoagulable workup. Vitamin supplementation with folic acid (B(9)), pyridoxine hydrochloride (B(6)), and cyanocobalamin (B(12)) may result in healing of cutaneous ulcerations in some patients with MTHFR mutations.

  2. A challenging diagnosis: case report of extensive pyoderma gangrenosum at multiple sites

    PubMed Central

    Ye, Mingwei J; Ye, Joshua Mingsheng; Wu, Leonard; Keating, Cameron P; Choi, Wai-Ting

    2014-01-01

    Background Pyoderma gangrenosum (PG) is a rare dermatological condition characterized by the rapid progression of a painful, necrolytic ulcer with an irregular, undermined border and commonly affects the lower extremities, mainly in the pretibial area. The diagnosis of PG is not easy. Due to lack of diagnostic laboratory test and histopathological findings indicative of PG, it is often misdiagnosed as an infection. This results in delayed or inappropriate treatment of the condition, which leads to devastating consequences such as limb amputation and death. Main observations We report a rare case of a 51-year-old female who was initially diagnosed as having infected ulcers and underwent serial debridements, which resulted in extensive PG at three different sites (abdominal, left thigh, and sacral). Conclusion This case highlights the challenges in diagnosing PG, emphasizes the key clinical features to aid diagnosis, and the clinical consequences of delayed or misdiagnosis of this condition. PMID:24741322

  3. Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne).

    PubMed

    Demidowich, Andrew P; Freeman, Alexandra F; Kuhns, Douglas B; Aksentijevich, Ivona; Gallin, John I; Turner, Maria L; Kastner, Daniel L; Holland, Steven M

    2012-06-01

    To describe the genotypes, phenotypes, immunophenotypes, and treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), a rare autoinflammatory disease, in 5 patients. Clinical information was gathered from medical records and through interviews with 5 patients from 4 kindreds. PSTPIP1 (CD2BP1) exon 10 and exon 11 sequencing was performed in each patient. Neutrophil granule content and cytokine levels were determined in plasma and stimulated peripheral blood mononuclear cells (PBMCs) from patients and controls. We identified 2 previously described PAPA syndrome-associated PSTPIP1 mutations, A230T and E250Q, and a novel change, E250K. Disease penetrance was incomplete, with variable expressivity. The cutaneous manifestations included pathergy, cystic acne, and pyoderma gangrenosum. Interleukin-1β (IL-1β) and circulating neutrophil granule enzyme levels were markedly elevated in patients compared to those in controls. PBMC stimulation studies demonstrated impaired production of IL-10 and enhanced production of granulocyte-macrophage colony-stimulating factor. Good resolution of pyoderma gangrenosum was achieved in 3 patients with tumor necrosis factor α (TNFα) blockade treatment. This analysis of 5 patients demonstrates that mutations in PSTPIP1 are incompletely penetrant and variably expressed in the PAPA syndrome. Neutrophil granule proteins are markedly elevated ex vivo and in the plasma, and elevated levels might be compatible with a diagnosis of PAPA syndrome. TNFα blockade appears to be effective in treating the cutaneous manifestations of PAPA syndrome. Copyright © 2012 by the American College of Rheumatology.

  4. Staged correction of an equinovarus deformity due to pyoderma gangrenosum using a Taylor spatial frame and tibiotalar calcaneal fusion with an intramedullary device.

    PubMed

    Bellamy, Jaime L; Holland, Courtney A; Hsiao, Mark; Hsu, Joseph R

    2011-11-01

    Pyoderma gangrenosum is a rare autoinflammatory syndrome manifested by skin lesions eventually creating ulcers. Surgical management can lead to scarring and contracture at the site of the lesion due to the pathergy phenomenon. A 43-year-old woman presented with a 5-year history of severe equinovarus deformity due to chronic pyoderma gangrenosum on her posteromedial ankle. She underwent a staged fusion. A gradual "closed" correction was performed in a Taylor spatial frame for 8 weeks in order to obviate the need for a surgical release in the area of the ulcer. She was ambulatory and full weight-bearing within 4 weeks of her frame removal. She maintained her correction with an accommodative foot orthosis until she had an uneventful tibiotalar calcaneal fusion with an intramedullary device. This case represents the success of using a Taylor spatial frame for staged fusion involving soft-tissue correction of severe, rigid equinovarus deformity due to pyoderma gangrenosum.

  5. Pyoderma gangrenosum with pathergy: A potentially significant complication following breast reconstruction.

    PubMed

    Patel, D K; Locke, M; Jarrett, P

    2017-07-01

    The failure of postoperative surgical site infection to resolve after appropriate antibiotic therapy should alert the clinician to other diagnoses. Pyoderma gangrenosum (PG) is an inflammatory neutrophilic dermatosis that is typically characterized by necrotizing ulceration. PG can be exacerbated by minor trauma leading to exaggerated skin injury, a condition known as pathergy. We present a case series of PG arising after immediate reconstruction for breast oncological surgery from 1st January 2006 to 1st September 2014. 395 immediate breast reconstructions were performed in 335 patients. Three cases of post-surgical PG were identified (0.9%), all in the setting of mastectomy for breast cancer. Two cases underwent immediate reconstruction with pedicled transverse rectus abdominus myocutaneous flaps, and one underwent submuscular expander insertion. A mean delay of 6.3 days was observed from first presentation of symptoms to diagnosis of PG. Immunosuppressants commonly used included methylprednisolone, prednisone, and ciclosporin, with good success at halting disease progress. Significant scarring affected all three women. Once the disease was deemed quiescent, intravenous immunoglobulin used in the perioperative period for further surgical procedures provided favorable results. A diagnostic algorithm is suggested to guide surgeons in investigations and management when post-surgical PG is suspected. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Pyoderma Gangrenosum: A Rare Cause of Cutaneous Ulceration and One Easily Misdiagnosed

    PubMed Central

    Walsh, Maureen Y.; Hoey, Susannah E.; O'Kane, Donal

    2016-01-01

    Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis often misdiagnosed. It is uncommon in infants and children accounting for 4% of cases. A one-year-old male in paediatric ICU ventilated for bronchopneumonia was referred with ulcerated areas on his neck and axilla corresponding to sites of recent removal of central and arterial lines. Examination revealed areas of deep ulceration with violaceous undermined borders in keeping with PG. This was supported by a skin biopsy showing a neutrophilic infiltrate in the deeper dermis. Topical clobetasol propionate was commenced and a dramatic improvement within 24 hours noted. Blood results showed a leucocytosis of 29.7; a differential WCC showed toxic granulation in neutrophils with myeloid left shift; immunoglobulins showed elevated IgG 23 and IgA 4.86. The elevated WCC made us consider a leukaemic trigger; however, they settled with treatment of the underlying infection. PG in children is more likely to have an atypical distribution involving the head and neck (26.6%) or buttocks (15%). An interesting feature in this case is the presence of pathergy, a term used to describe the induction or exacerbation of PG at sites of iatrogenic or incidental trauma. It is seen in 31% of patients with PG. PMID:27738542

  7. Topical Medical Cannabis (TMC): A new treatment for wound pain-Three cases of Pyoderma Gangrenosum.

    PubMed

    Maida, Vincent; Corban, Jason

    2017-08-14

    Pain associated with integumentary wounds is highly prevalent yet it remains an area of significant unmet need within healthcare. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated. The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, non-invasive, self-administered, and display rapid onset of analgesia. Extracts derived from the cannabis plant have been applied to wounds for thousands of years. The discovery of the human endocannabinoid system and its dominant presence throughout the integumentary system provides a valid and logical scientific platform to consider the use of topical cannabinoids for wounds. We are reporting a prospective case series of 3 patients with Pyoderma Gangrenosum (PG) that were treated with Topical Medical Cannabis (TMC) compounded in non-genetically modified organic sunflower oil. Clinically significant analgesia that was associated with reduced opioid utilization was noted in all 3 cases. TMC has the potential to improve pain management in patients suffering from wounds of all classes. Copyright © 2017. Published by Elsevier Inc.

  8. Pyoderma gangrenosum, acne and suppurative hidradenitis syndrome following bowel bypass surgery.

    PubMed

    Marzano, Angelo V; Ishak, Rim S; Colombo, Antonella; Caroli, Francesco; Crosti, Carlo

    2012-01-01

    The clinical triad of pyoderma gangrenosum (PG), acne and suppurative hidradenitis (PASH) has recently been described as a new disease entity within the spectrum of autoinflammatory syndromes, which are an emerging group of inflammatory diseases distinct from autoimmune, allergic and infectious disorders. PASH syndrome is similar to PAPA (pyogenic arthritis, acne and PG), but it differs in lacking the associated arthritis and on a genetic basis. PAPA syndrome is caused by mutations in a gene involved in the regulation of innate immune responses, the PSTPIP1, while no mutations have been detected to date in patients with PASH syndrome. We report a young male patient who developed coexisting disseminated PG, typical suppurative hidradenitis and acneiform eruption on the face, after he had undergone bowel bypass surgery for obesity. The cutaneous manifestations associated with bowel bypass syndrome often mimic PG or other neutrophilic dermatoses, suggesting a pathogenesis related to neutrophil-mediated inflammation for this condition. This is the first report describing PASH syndrome after bariatric surgery, and we propose to include such neutrophilic dermatoses in the list of complications occurring after bowel bypass surgery. Extensive genetic studies may help to clarify the etiopathogenesis of PASH as well as of autoinflammatory diseases in general.

  9. Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients.

    PubMed

    Join-Lambert, Olivier; Duchatelet, Sabine; Delage, Maïa; Miskinyte, Snaigune; Coignard, Hélène; Lemarchand, Nicolas; Alemy-Carreau, Murielle; Lortholary, Olivier; Nassif, Xavier; Hovnanian, Alain; Nassif, Aude

    2015-11-01

    Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases.

  10. Pyoderma gangrenosum: a difficult diagnosis best managed in a burn treatment center.

    PubMed

    Stair-Buchmann, Megan E; Ackerman, Bruce H; Reigart, Cynthia L; Haith, Linwood R; Patton, Mary L; Guilday, Robert E

    2015-01-01

    Pyoderma gangrenosum (PG) is a rare immunological disorder with inexplicable white blood cell infiltration into the epidermis with necrosis and excruciating pain. Diagnosis is by exclusion which delays proper treatment. Surgical intervention often exacerbates wounds. Between 2004 and 2010, seven patients with PG were admitted to our burn treatment center (BTC). Multiple treatment modalities were used on these patients. An institutional review board-approved retrospective study investigated seven PG BTC admissions. Demographic information, symptom onset, time to diagnosis, admission or transfer, length of stay (LOS), use of corticosteroids, and prior surgery were collected. The average time to PG diagnosis was 18.7 days and the average wound surface area was 3.9%. The average patient age was 64.6 years (median 66 years) and there were five men and two women patients. The average symptom onset was 70.5 days prior to BTC admission. The BTC wound care lasted 24 days. Six of the seven patients had lower extremity lesions vs one with lesions involving the abdomen. Inflammatory bowel disease was noted in two patients, one with malignant melanoma, and another with psoriasis. Corticosteroids were begun 1.75 days after admission for six of the seven patients. Of the seven PG patients, five had excision and/or skin grafting with vacuum-assisted wound closure used in four. Six patients were discharged, but one patient succumbed early to sepsis. Skin grafting often speeds up chronic wound closure; however for PG this causes progression of lesions. Persistent non-healing wounds with pain disproportionate to size may be PG. Prompt diagnosis and BTC specialized care greatly improve outcomes for PG patients.

  11. Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: A prospective cohort study.

    PubMed

    Thomas, Kim S; Ormerod, Anthony D; Craig, Fiona E; Greenlaw, Nicola; Norrie, John; Mitchell, Eleanor; Mason, James M; Johnston, Graham A; Wahie, Shyamal; Williams, Hywel C

    2016-11-01

    Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG. This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence. Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence. Our study did not include a randomized comparator. Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  12. Pyoderma Gangrenosum after Deep Inferior Epigastric Perforator Breast Reconstruction: Systematic Review and Case Report.

    PubMed

    Zelones, Justin T; Nigriny, John F

    2017-04-01

    Pyoderma gangrenosum (PG) is a rare skin disorder of the neutrophilic dermatoses spectrum that can mimic wound infections in surgical patients. PG after breast surgery has been reported but in limited amounts in autologous breast reconstruction patients. We present the first case of PG after a delayed bilateral deep inferior epigastric perforator flap breast reconstruction in the setting of systemic disease along with a systematic review. PubMed, Ovid, and Web of Science were systematically searched to obtain cases of PG after autologous breast reconstruction. Sixty articles were identified but only 16 were relevant to this study. Systemic disease was present in 2 patients (13%). Wound onset occurred typically 5 days after surgery. Fever and/or leukocytosis was observed in 10 patients (63%). Wound cultures were positive in 2 patients (13%). Donor-site wounds were present in 9 patients (56%). Bilateral breast wounds were present in 67% of bilateral cases. Debridement was performed in 10 cases (63%). Skin graft or substitute was performed in 6 cases (38%). Resection of autologous flap was performed in 3 cases (19%). All patients were treated with systemic steroids (81%) and/or immunosuppressive medications (50%). Complete wound healing occurred by 4 months on average. If early ulcerative wounds develop at multiple sites after autologous breast reconstruction with worsening after debridement and antibiotic therapy, then PG should be considered. It is imperative that an early diagnosis and subsequent treatment with steroids and/or immunosuppressive medications be initiated so further surgical procedures, flap loss, and scarring can be minimized.

  13. Pyoderma gangrenosum preceding the onset of extranodal natural killer/T-cell lymphoma

    PubMed Central

    Yang, Ting-Hua; Hu, Chung-Hong; Tsai, Hsiou-Hsin

    2016-01-01

    Abstract Introduction: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that may be associated with systemic diseases. The association of PG with lymphoid malignancies has rarely been reported. Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive entity with a poor prognosis. Here, we report the case of a patient who had idiopathic PG refractory to systemic steroids and subsequently developed ENKTL. Case report: A 70-year-old man presented with a 2-month history of intermittent fever and multifocal painful papules, plaques, and ulcerations on his extremities. The histological and culture results of the lesions were consistent with those of PG. A thorough work-up was performed and did not demonstrate any underlying systemic diseases including malignancy. The PG lesions were refractory to systemic steroid therapy. An enlarging nodule was observed over his right infraorbital area 4 months after the onset of the skin eruptions. The nodule was later biopsied and diagnosed as ENKTL by using histopathological and immunohistochemical studies. Fludeoxyglucose positron emission tomography/computed tomography revealed multiple intense fludeoxyglucose-avid masses in the bones and lungs, suggesting multiorgan metastases. The patient rejected chemotherapy and died 4 weeks after the diagnosis. Conclusion: The present case indicates that in any patient with idiopathic PG refractory to conventional therapy, the presence of any underlying disease or malignancy must be thoroughly evaluated. The present case serves as a reminder that when assessing patients with PG, clinicians should increase their awareness regarding the delayed association with malignancy, even in the absence of a concomitant systemic disease at presentation. Furthermore, the prompt evaluation of any suspicious lesions in the context of PG for the possibility of a malignant nature can improve the prognosis, particularly in cases of aggressive malignancy. Understanding the cutaneous

  14. Leukocyte adhesion deficiency-I with a novel intronic mutation presenting with pyoderma gangrenosum- like lesions.

    PubMed

    Madkaikar, Manisha; Italia, Khushnooma; Gupta, Maya; Desai, Mukesh; Aggarwal, Amita; Singh, Surjit; Suri, Deepti; Mishra, Anju; Chavan, Sushant; Ghosh, Kanjaksha; Sarangal, Rishu; Dogra, Sunil

    2015-05-01

    Pyoderma gangrenosum (PG) is an uncommon noninfectious neutrophilic dermatosis characterized by recurrent, sterile, necrotic skin ulcers. It is commonly associated with underlying systemic disease like inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Pathogenesis of PG remains unclear though aberrant immune responses have been implicated. The diagnosis of PG is of exclusion and management is empirical with local or systemic immunosuppressive therapy. LAD-I is a rare form of autosomal recessive disorders caused by mutations of the gene ITGB2, clinically characterized by recurrent severe bacterial infection, impaired pus formation, poor wound healing and persistent neutrophilia. Though skin ulcerations are common, predominant clinical presentation as PG is unusual in LAD-I. Here we present four Indian patients with LAD-I from three unrelated families initially diagnosed as PG due to chronic recurrent skin ulcerations requiring steroids and antibiotics for healing, associated with atrophic scar formation. All these four patients had persistent neutrophilia without history of delayed cord separation and showed moderate expression of CD18 (19 to 68%) on neutrophils. Sequencing of the entire coding region and intronic splice sites of the ITGB2 gene from the genomic DNA of these patients revealed a novel common mutation IVS10+4A>G. LAD-I should be kept in mind while evaluating patients with PG especially those with persistent neutrophila in the absence of other rheumatological disorders. Diagnosis of LAD-I in these cases is extremely important for management as treating these patients without adequate antibiotic cover may prove fatal and these patients often require hematopoietic stem cell transplantation for permanent cure.

  15. Coexistence of pyoderma gangrenosum and sweet's syndrome in a patient with ulcerative colitis.

    PubMed

    Ajili, Faida; Souissi, Asmahan; Bougrine, Fathi; Boussetta, Najah; Abdelhafidh, Nadia Ben; Sayhi, Sameh; Louzir, Bassem; Doss, Nejib; Laabidi, Janet; Othmani, Salah

    2015-01-01

    Pyoderma gangrenosum (PG) and Sweet's Syndrome (SS) are inflammatory skin diseases caused by the accumulation of neutrophils in the skin and, rarely, in internal organs. These neutrophilic dermatosis (NDs) are distinguished by the existence of forms of transition or overlap. They are frequently associated to systemic diseases especially hematologic and gastrointestinal ones. We report a case of a patient with ulcerative colitis (UC) who successively developed two types of NDs: PG then SS. A 66 years old patient with a history of UC consulted in July 2012 for an erythematous swelling of the back of the right hand treated with antibiotics without improvement. At that time, bacteriological samples were negative. In October 2012, he was hospitalized for polyarthralgia and impaired general condition. In physical examination, he had vesiculobullous plaque of 10 cm long of the right hand and wrist, infiltrated erythematous plaque on the right leg and another topped with a large pustule at the left ankle. Skin biopsy showed at the back of the right hand an aspect of PG and at the infiltrated plaques of the ankle an aspect of SS. Prednisone was started with improvement of the skin lesions and a recovery condition. The combination of PG and SS has already been described in cases of hematologic malignancy and rarely in UC. There is also the notion of passage from a neutrophilic dermatosis to another. Indeed, a typical lesion initially of SS can evolve to a future PG. This case demonstrates that neutrophilic dermatoses form a continous spectrum of entities that may occur in UC.

  16. Successful Treatment of Pyoderma Gangrenosum after Augmentation Mastopexy Using Vacuum Therapy

    PubMed Central

    Soncini, Julio Alberto; Frizzo Neto, Juvenal Antonio; Gemperli, Rolf

    2016-01-01

    Background: Pyoderma gangrenosum (PG) is a rare, severe, destructive neutrophilic dermatosis characterized by a progressive, necrotizing process after skin injury. Its cause is still unknown, and diagnosis represents a challenge when ulcers are seen after surgery. Bacterial infection is not found in the wounds. Patients exhibit “pathergy” with the appearance of new lesions after local trauma such as surgical procedures, debridements, and wound care, suggesting altered inflammatory response. The objective of this study was to review the literature and report a case of PG that was satisfactorily treated with vacuum therapy (vacuum-assisted closure [VAC]). Case Report: A 19-year-old healthy patient presented with skin ulceration 4 days after augmentation mastopexy, progressing to extensive necrosis. On the eighth day, she underwent debridement and implant removal. Two days later, the necrotic process was again evident and progressed, resulting in a significant increase in wound size, with each wound reaching 20 × 25 cm. Intense and diffuse neutrophilic exudate and areas of necrosis were present. Systemic corticosteroids and VAC under general anesthesia were initiated 5 days after the second surgery. From the fourth VAC session, some adherence between the mammary gland and pectoral muscles was visible, so deep sutures avoiding the dermis were placed to direct wound closure. Conclusions: PG is a life-threatening complication with devastating outcomes. Early diagnosis is critical. Although some reported cases needed up to 2 years for wound closure, in this case, VAC therapy allowed the patient to be discharged after only 42 days and permitted wound closure without the need for skin grafts. PMID:27975008

  17. Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high synovial cell counts.

    PubMed

    Löffler, W; Lohse, P; Weihmayr, T; Widenmayer, W

    2017-03-01

    Pyogenic arthritis, pyoderma gangrenosum and acne syndrome was diagnosed in a 42-year-old patient, after an unusual persistency of high synovial cell counts had been noticed. Clinical peculiarities and problems with diagnosing septic versus non-septic arthritis are discussed.

  18. An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum.

    PubMed

    Foss, C E; Clark, A R; Inabinet, R; Camacho, F; Jorizzo, J L

    2008-08-01

    Pyoderma gangrenosum (PG) is a chronic inflammatory disease that causes painful cutaneous ulcers that are difficult to treat. Currently, systemic immunosuppressants, often including prednisone, are the mainstay of therapy. Long-term therapy with these agents is often required which exposes patients to possible adverse effects. An alternative treatment that is safe and effective is truly needed. To study the efficacy and safety of alefacept, which inhibits T-cell activation and selectively reduces the T-cell population, for treatment of PG. In this prospective open-label pilot study, four patients diagnosed with PG received weekly doses of 15 mg alefacept intramuscularly for 20 weeks with 12-week treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving remission as defined by a Physician Global Assessment (PGA) of 'clear' or 'almost clear.' Secondary endpoints included proportion of patients achieving 50% improvement in PG lesion size (measured in mm) and proportion of patients achieving resolution of inflammation (an erythema score of 0 and a border thickness of 0 on scales of 0-4). By week 20, one (25%) of the four patients achieved remission, two showed marked improvement in severity on PGA, and one had slight improvement. One patient showed a 98% decrease in lesion size; two other patients evidenced a decrease in the number of small lesions as well as improvements in primary lesion sizes, but did not surpass the 50% criterion. All four patients showed improved erythema scores during treatment, though only one patient showed a complete resolution of inflammation. It may be difficult to generalize the results of this study to a larger population of patients with PG due to the small sample size and lack of a control group. A longer treatment interval might have been required. Safety and efficacy of long-term therapy is unknown. In this pilot study it appears that alefacept treatment may significantly reduce PG severity

  19. Pyoderma gangrenosum following complex reconstruction of a large-scale lower limb defect by combined Parascapular and latissimus dorsi flap

    PubMed Central

    Cordts, Tomke; Bigdeli, Amir K.; Harhaus, Leila; Hirche, Christoph; Kremer, Thomas; Kneser, Ulrich; Schmidt, Volker J.

    2017-01-01

    A female patient with a critical soft tissue defect after elective knee replacement surgery was transferred to our department for reconstruction. As wounds were rapidly progressing, necrotizing fasciitis was initially suspected but eventually ruled out by histopathological analysis. A 50 × 15 cm defect was then reconstructed by means of a combined Parascapular and latissimus dorsi flap before, a couple days later, the patient developed tender pustules and ulcers involving the flap as well as the donor site. Attempts of excising necrotic areas not only continued to fail but seemed to worsen the patient's wound and overall condition. Eventually, pyoderma gangrenosum (PG) was diagnosed and local and systemic therapy was initiated but treatment proved to be challenging and insufficient at first. Being an extremely aggressive disease, early diagnosis is crucial and PG should always be suspected when rapidly progressive ulceration on surgical sites is observed. PMID:28096323

  20. Case with pyoderma gangrenosum abruptly emerging around the wound of cesarean section for placenta previa with placenta accrete.

    PubMed

    Nonaka, Taro; Yoshida, Kunihiko; Yamaguchi, Masayuki; Aizawa, Atsuko; Fujiwara, Hiroshi; Enomoto, Takayuki; Takakuwa, Koichi

    2016-09-01

    A 39-year-old woman underwent emergency cesarean section (CS) due to placenta previa totalis with massive bleeding. Two major problems emerged in this patient after CS was carried out. One was partial retention of the placenta due to placenta accreta. Another major and more serious problem was pyoderma gangrenosum (PG) widely appearing at the skin of the abdomen around the CS wound. Conservative treatment was performed for the retained placenta, and it had completely disappeared by 76 days after the CS. The diagnosis of PG was promptly made in consultation with a plastic surgeon and a dermatologist when a wide ulcer emerged around the CS wound, and high-dose prednisolone was administered as treatment. At 90 days following the CS, near-complete epithelialization was achieved. This extremely rare case reflects the importance of rapid diagnosis and treatment of PG. © 2016 Japan Society of Obstetrics and Gynecology.

  1. Recurrent pyoderma gangrenosum after cesarean delivery successfully treated with vacuum-assisted closure and split thickness skin graft: a case report.

    PubMed

    Aydın, Serdar; Aydın, Çağrı Arıoğlu; Uğurlucan, Funda Güngör; Yaşa, Cenk; Dural, Özlem

    2015-04-01

    We describe the case of a 32-year-old woman (gravidity: 4; parity: 2) who underwent cesarean delivery at 37 weeks of gestation and presented with dehiscence and infection of the surgical wound. She had a history of wound infection and dehiscence of the scar from a previous cesarean delivery and dehiscence in the dorsal side of her left hand at the site of intravenous catheterization. The patient was initially diagnosed with a skin infection and later with pyoderma gangrenosum. No evidence of any underlying disease was found. The lesions were treated with systemic corticosteroids and azathioprine, but the lesions were unresponsive to treatment. This complicated case of pyoderma gangrenosum after cesarean delivery, which initially mimicked wound infection, was successfully treated with vacuum-assisted closure and split-thickness skin graft. This synergistic approach with vacuum-assisted closure could be an important treatment option for aggressive and slow-healing lesions.

  2. Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.

    PubMed

    Ormerod, Anthony D; Thomas, Kim S; Craig, Fiona E; Mitchell, Eleanor; Greenlaw, Nicola; Norrie, John; Mason, James M; Walton, Shernaz; Johnston, Graham A; Williams, Hywel C

    2015-06-12

    To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. Multicentre, parallel group, observer blind, randomised controlled trial. 39 UK hospitals, recruiting from June 2009 to November 2012. 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was -0.21 (1.00) cm(2)/day in the ciclosporin group compared with -0.14 (0.42) cm(2)/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm(2)/day, 95% confidence interval -0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in

  3. Pyoderma gangrenosum (PG) associated with levamisole-adulterated cocaine: Clinical, serologic, and histopathologic findings in a cohort of patients.

    PubMed

    Jeong, Haneol S; Layher, Heather; Cao, Lauren; Vandergriff, Travis; Dominguez, Arturo R

    2016-05-01

    Recently, isolated reports of pyoderma gangrenosum (PG) secondary to levamisole-contaminated cocaine have been described, with similar serologic findings to the vasculopathic presentation. We sought to describe clinical, histopathological, and serologic findings in 8 patients with PG associated with levamisole-contaminated cocaine. Eight consecutive patients presenting with this disease spanning the period from 2011 to 2015 were included for the cohort. Observed variables included: lesion distribution, morphology, serologic titers, and histopathologic evaluation for vasculitis and vasculopathy. All patients reported cocaine exposure prior to the onset of lesions resembling PG. Lesions appeared primarily on the upper (6 of 8 patients) and lower (all 8 patients) extremities. Most patients demonstrated elevated titers for p-ANCA and antiphospholipid antibodies, and a diffuse dermal infiltrate dominated by neutrophils was seen in all biopsy specimens. Lesions improved or remained stable with conservative management or short courses of steroids, and recurrence was only noted on re-exposure to adulterated cocaine. The study is limited by sample size. PG may occur after exposure to levamisole-adulterated cocaine. Clinical and histopathological findings resemble those seen in conventional forms of PG, whereas serologic findings mirror those seen in other levamisole-associated vasculopathic or vasculitic eruptions. Cocaine avoidance represents a cornerstone of management in these patients. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Novel PSTPIP1 gene mutation in a patient with pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.

    PubMed

    Lindwall, Elvira; Singla, Shikha; Davis, William E; Quinet, Robert J

    2015-08-01

    Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant disease that usually presents in childhood with recurrent sterile arthritis. As the child ages into puberty, cutaneous features develop and arthritis subsides. We report the case of a now 25-year-old male patient with PAPA syndrome with the E250K mutation in PSTPIP1. We also present a systematic literature review of other PAPA cases. We conducted a literature search of PubMed using the following search terms: E250K mutation, PSTPIP1, and PAPA. PAPA syndrome is caused by mutations on chromosome 15q affecting the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene, also known as CD2-binding protein 1 (CD2BP1). The reported cases of PAPA syndrome currently in the literature involve mutations in A230T and E250Q. One case of a novel E250K mutation has been reported, which presented with a different phenotype to previously described cases of PAPA syndrome. With variation present between disease presentations from case to case, it is possible that the spectrum of PAPA syndrome is wider than currently thought. Further research is needed which may uncover an as-yet undiscovered genetic abnormality linking these interrelated diseases together. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) associated with hypogammaglobulinemia and elevated serum tumor necrosis factor-alpha levels.

    PubMed

    Edrees, Amr F; Kaplan, David L; Abdou, Nabih I

    2002-10-01

    Pyogenic aseptic arthritis, pyoderma gangrenosum, and cystic acne (PAPA) syndrome is an unusual triad that was recently mapped to a chromosome 15q mutation. We describe a patient from this kindred in whom hypogammaglobulinemia and elevated tumor necrosis factor-alpha serum levels were detected. The patient responded well to intravenous gammaglobulin and intra-articular corticosteroid therapy. Immune abnormalities can be found in PAPA syndrome and could be the consequence of the chromosomal abnormalities affecting candidate genes on this chromosome with subsequent abnormalities in cytokine or chemokine secretion. Rheumatologists should be alert for this syndrome. Correction of the immune abnormalities may be effective in controlling the disease manifestations.

  6. Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases.

    PubMed

    Marzano, Angelo V; Ceccherini, Isabella; Gattorno, Marco; Fanoni, Daniele; Caroli, Francesco; Rusmini, Marta; Grossi, Alice; De Simone, Clara; Borghi, Orietta M; Meroni, Pier Luigi; Crosti, Carlo; Cugno, Massimo

    2014-12-01

    The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.

  7. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome.

    PubMed

    Ursani, Mohammad A; Appleyard, Joan; Whiteru, Onome

    2016-08-17

    BACKGROUND Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). CASE REPORT A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. CONCLUSIONS Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various auto-inflammatory disorders may share pathogenic commonalities.

  8. Associated factors and comorbidities in patients with pyoderma gangrenosum in Germany: a retrospective multicentric analysis in 259 patients

    PubMed Central

    2013-01-01

    Background Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG. Methods Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany. Results We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8%) patients were female, 117 (45.2%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6% with anemia, 44.8% with endocrine diseases, 12.4% with internal malignancies, 9.3% with chronic inflammatory bowel diseases and 4.3% with elevated creatinine levels. Moreover 25.5% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome. Conclusions Our study describes one of the world’s largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients’ characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients. PMID:24010984

  9. Pyogenic Arthritis, Pyoderma Gangrenosum, Acne, Suppurative Hidradenitis (PA-PASH) Syndrome: An Atypical Presentation of a Rare Syndrome

    PubMed Central

    Ursani, Mohammad A.; Appleyard, Joan; Whiteru, Onome

    2016-01-01

    Patient: Male, 44 Final Diagnosis: PAPASH syndrome Symptoms: Recurrent skin ulcers • diarrhea • inflammatory arthritis Medication: Prednisone • anti-tumor necrosis factor Clinical Procedure: N/A Specialty: Rheumatology Objective: Rare disease Background: Pyogenic arthritis, pyoderma gangrenosum (PG), acne, and suppurative hidradenitis (PA-PASH) syndrome has been linked to an auto-inflammatory pathway. We report a case that is an atypical presentation of a rare syndrome, which supports literature suggesting that different phenotypes of PG-related syndromes may be a variation of the same pathogenic spectrum. Interestingly, our patient displayed a positive proteinase-3 antibody (PR-3). The clinical relevance of this is unclear. In recent literature, antineutrophil cytoplasmic autoantibodies (ANCA) positivity has been reported in various inflammatory conditions other than ANCA-associated vasculitis (AAV). Case Report: A 44-year-old African American male with history of pyogenic arthritis, acne, suppurative hidradenitis, and chronic diarrhea presented for evaluation of painful ulcers located on the bilateral lower extremities, bilateral proximal interphalangeal joints, buttocks, and scrotum, and chronic diarrhea. Infectious etiologies for the ulcers were ruled out. Biopsy of an ulcer revealed PG. Colonoscopy revealed inflammation and ulceration with biopsy consistent with ulcerative colitis (UC). After treatment with prednisone, the ulcers healed within 4 weeks, and the chronic diarrhea resolved. Conclusions: Our patient displayed a variation of PA-PASH syndrome and UC. Previously reported cases of similar phenotypes of PG-related syndromes have not presented in this fashion. Furthermore, the literature does not report cases of PG-related syndromes with an elevation in PR-3 antibody. Elevation in PR-3 has been reported in various inflammatory disorders aside from AAV. The relevance of this is currently unclear. It may be possible that the milieus of these various

  10. Association of Pyoderma Gangrenosum, Acne, and Suppurative Hidradenitis (PASH) Shares Genetic and Cytokine Profiles With Other Autoinflammatory Diseases

    PubMed Central

    Marzano, Angelo V.; Ceccherini, Isabella; Gattorno, Marco; Fanoni, Daniele; Caroli, Francesco; Rusmini, Marta; Grossi, Alice; De Simone, Clara; Borghi, Orietta M.; Meroni, Pier Luigi; Crosti, Carlo; Cugno, Massimo

    2014-01-01

    Abstract The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin. PMID:25501066

  11. Clinical, serologic, and genetic factors associated with pyoderma gangrenosum and erythema nodosum in inflammatory bowel disease patients

    PubMed Central

    Weizman, Adam; Huang, Brian; Berel, Dror; Targan, Stephan R.; Dubinsky, Marla; Fleshner, Phillip; Ippoliti, Andrew; Kaur, Manreet; Panikkath, Deepa; Brant, Steve; Oikonomou, Ioannis; Duerr, Rick; Rioux, John; Silverberg, Mark; Rotter, Jerome I; Vasiliauskas, Eric; Haritunians, Talin; Shih, David; Li, Dalin; Melmed, Gil Y.; McGovern, Dermot P.B.

    2014-01-01

    Objective Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis. Design We performed a case control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG-) and EN (EN-). Data on clinical features were obtained by chart review. IBD related serology was determined using ELISA and genome-wide data generated using Illumina technology. Standard statistical tests for association were used. Results We identified a total 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN were available for serological analyses. Fewer male subjects were identified in the PG(+) (OR 0.6, p=0.009) and EN(+) groups (OR 0.31, p=0<0.0001). Colonic disease, previous IBD related surgery, and non-cutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared to controls. PG(+) was associated with ANCA seropositivity (p=0.03) and higher ANCA level (p=0.02) in CD. Genetic associations with PG included known IBD loci (IL8RA (p=0.00003), and PRDM1 (0.03)) as well as with USP15 (4.8×10−6) and TIMP3 (5.6 ×10−7). Genetic associations with EN included known IBD susceptibility genes (PTGER4 (p=8.8×10−4), ITGAL (0.03)) as well as SOCS5 (9.64×10−6), CD207 3.14×10−6), ITGB3 (7.56×10−6) and rs6828740 (4q26)(p <5.0 × 10−8). Multivariable models using clinical, serologic, and genetic parameters predicted PG (AUC 0.8) and EN (AUC 0.97). Conclusion Cutaneous manifestations in IBD are associated with distinctive genetic characteristics as well as with the similar clinical characteristics including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies. PMID:24487271

  12. Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet's syndrome

    PubMed Central

    Marzano, A V; Fanoni, D; Antiga, E; Quaglino, P; Caproni, M; Crosti, C; Meroni, P L; Cugno, M

    2014-01-01

    Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are two inflammatory skin diseases presenting with painful ulcers and erythematous plaques, respectively; both disorders have a debilitating clinical behaviour and PG is potentially life-threatening. Recently, PG and SS have been included among the autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. However, an autoinflammatory pattern clearly supporting this inclusion has never been demonstrated. We studied 16 patients with PG, six with SS and six controls, evaluating, using a sandwich-based protein antibody array method, the expression profile of inflammatory effector molecules in PG, SS and normal skin. The expressions of interleukin (IL)-1 beta and its receptor I were significantly higher in PG (P = 0·0001 for both) and SS (P = 0·004–0·040) than in controls. In PG, chemokines such as IL-8 (P = 0·0001), chemokine (C-X-C motif) ligand (CXCL) 1/2/3 (P = 0·002), CXCL 16 (P = 0·003) and regulated upon activation normal T cell expressed and secreted (RANTES) (P = 0·005) were over-expressed. In SS, IL-8 (P = 0·018), CXCL 1/2/3 (P = 0·006) and CXCL 16 (P = 0·036) but not RANTES were over-expressed, suggesting that chemokine-mediated signals are lower than in PG. Fas/Fas ligand and CD40/CD40 ligand systems were over-expressed in PG (P = 0·0001 for Fas, P = 0·009 for Fas ligand, P = 0·012 for CD40, P = 0·0001 for CD40 ligand), contributing to tissue damage and inflammation, while their role seems to be less significant in SS. Over-expression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that PG and SS are autoinflammatory diseases. The differences in expression profile of inflammatory effectors between these two disorders may explain the stronger local aggressiveness in PG than SS. PMID:24903614

  13. Atypical severe combined immunodeficiency caused by a novel homozygous mutation in Rag1 gene in a girl who presented with pyoderma gangrenosum: a case report and literature review.

    PubMed

    Patiroglu, Turkan; Akar, H Haluk; Gilmour, Kimberly; Ozdemir, M Akif; Bibi, Shahnaz; Henriquez, Frances; Burns, Siobhan O; Unal, Ekrem

    2014-10-01

    Severe combined immunodeficiency (SCID) is a heterogeneous group of inherited defects involving the development of T- and/or B-lymphocytes. We report a female with atypical severe combined immunodeficiency caused by a novel homozygous mutation at cDNA position 2290 (c.2290C > T) in exon 2 of the RAG1 gene. The patient presented with bronchopneumonia, pyoderma gangrenosum (PG), pancytopenia and splenomegaly. She presented to us with pancytopenia and splenomegaly at the age of 11. Her condition was complicated by PG on left lower ankle at the age of 12. She experienced bronchopneumonia at the age of 15. She was diagnosed with RAG1 deficiency at the age of 16. Her immunological presentation included leucopenia and diminished number of B cells.

  14. Inflammation in mice ectopically expressing human Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome-associated PSTPIP1 A230T mutant proteins.

    PubMed

    Wang, Donghai; Höing, Susanne; Patterson, Heide Christine; Ahmad, Umtul M; Rathinam, Vijay A K; Rajewsky, Klaus; Fitzgerald, Katherine A; Golenbock, Douglas T

    2013-02-15

    Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA syndrome) is an autoinflammatory disease caused by aberrant production of the proinflammatory cytokine interleukin-1. Mutations in the gene encoding proline serine threonine phosphatase-interacting protein-1 (PSTPIP1) have been linked to PAPA syndrome. PSTPIP1 is an adaptor protein that interacts with PYRIN, the protein encoded by the Mediterranean Fever (MEFV) gene whose mutations cause Familial Mediterranean Fever (FMF). However, the pathophysiological function of PSTPIP1 remains to be elucidated. We have generated mouse strains that either are PSTPIP1 deficient or ectopically express mutant PSTPIP1. Results from analyzing these mice suggested that PSTPIP1 is not an essential regulator of the Nlrp3, Aim2, or Nlrc4 inflammasomes. Although common features of human PAPA syndrome such as pyogenic arthritis and skin inflammation were not recapitulated in the mouse model, ectopic expression of the mutant but not the wild type PSTPIP1 in mice lead to partial embryonic lethality, growth retardation, and elevated level of circulating proinflammatory cytokines.

  15. UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

    PubMed Central

    2012-01-01

    Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by

  16. UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

    PubMed

    Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

    2012-04-28

    Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and

  17. Pyoderma Gangranosum of the Penis

    PubMed Central

    Kim, Tae Heung; Oh, Seung Young

    2009-01-01

    We report a patient who developed pyoderma gangrenosum in the penis with invasion of the distal urethra. The patient was treated with prednisolone and thalidomide, followed by a reconstructive surgical repair using a scrotal island flap. We report this case with a brief review of the literature. PMID:19949683

  18. [Pathogenesis and prognosis of pyoderma gangrenosum (dermatitis ulcerosa) (author's transl)].

    PubMed

    Odeh, F

    1981-12-15

    The diagnosis of p. g. is based on clinical appearance. P. g. is frequently associated with systemic disease. This paper presents 23 cases of p. g. associated with other sufferings and a review of the Literature in which pathogenesis, prognosis, age and sex of this cutaneous disorder are standing in foreground for a discussion.

  19. Pyoderma Gangrenosum or Necrotising Fasciitis? Diagnostic and Therapeutic Wanderings.

    PubMed

    Vaysse-Vic, Mathieu; Mathieu, Pierre-Alain; AurélieCharissoux; Charissoux, Jean-Louis; Marcheix, Pierre-Sylvain

    2017-03-09

    A case of post-traumatic lower-limb pyodermagangrenosum (PG) in a 77-year-old female is reported. The diagnosis of PG is frequently one of exclusion, and it is therefore unsurprising that the condition was initially mistaken for necrotising fasciitis then for necrotising bacterial dermo-hypodermitis. Medical and surgical treatment for those conditionsproved ineffective. This fact, together with the atypical presentation, promoted a re-evaluation of the diagnosis. The clinical findings and investigation results converged to suggest PG, and a therapeutic trial was initiated. The good treatment response and negative findings from tests for other conditions established the diagnosis of post-traumatic PG.

  20. Diving with pre-existing medical conditions.

    PubMed

    Lippmann, John; McD Taylor, David; Stevenson, Christopher; Williams, Jo; Mitchell, Simon J

    2017-09-01

    This is the second report based on a survey of Divers Alert Network Asia-Pacific (DAN AP) members who dive with cardiovascular and respiratory conditions and diabetes. It examines the medical management of the divers' conditions, any diving modifications used to mitigate the risk and outcomes. An online cross-sectional survey was sent to 833 divers who had declared a targeted medical condition when applying for DAN AP membership between July 2009 and August 2013. Two-hundred-and-sixty-eight respondents (32%) provided sufficient information on their conditions to be included in the analyses. These included ischaemic heart disease (31), arrhythmias (20), cardiac septal defects (31), other cardiac conditions (10), hypertension (127), diabetes (25), asthma (40) and pneumothorax (5). Forty-nine per cent had sought specialist diving medical advice about their condition and 23% reported modifying their diving practices to mitigate their risk. The cohort had completed 183,069 career dives, 57,822 of these since being diagnosed with their medical condition. There were 27 individuals who reported having decompression illness (25 of whom were subsequently diagnosed with a persistent foramen ovale), and two individuals who experienced an arrhythmia during diving. Some DAN AP members are diving with medical conditions which could potentially impact the safety of their diving. A minority modified their diving practices to mitigate the risk of their condition and approximately half sought specialist diving medical advice. The incidence of diving-related problems precipitated by known and managed pre-existing health conditions seems low but further studies of larger cohorts and incorporating fatality data would be necessary to confirm this. These results are limited by the 32% response rate and potential for bias towards selection of those most careful with their health.

  1. 77 FR 52614 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... HUMAN SERVICES 45 CFR Part 152 RIN 0938-AQ70 Pre-Existing Condition Insurance Plan Program AGENCY... regarding program eligibility to the interim final regulation implementing the Pre- Existing Condition Plan... provide immediate access to coverage for eligible uninsured Americans with pre-existing...

  2. 5 CFR 2634.409 - Pre-existing trusts.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Pre-existing trusts. 2634.409 Section... FINANCIAL DISCLOSURE, QUALIFIED TRUSTS, AND CERTIFICATES OF DIVESTITURE Qualified Trusts § 2634.409 Pre-existing trusts. An interested party may place a pre-existing irrevocable trust into a qualified...

  3. 78 FR 30218 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... HUMAN SERVICES 45 CFR Part 152 RIN 0938-AQ70 Pre-Existing Condition Insurance Plan Program AGENCY... payment rates for covered services furnished to individuals enrolled in the Pre-Existing Condition... to eligible uninsured individuals with pre- existing conditions. A number of states elected...

  4. 17 CFR 151.9 - Pre-existing positions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Pre-existing positions. 151.9... FUTURES AND SWAPS § 151.9 Pre-existing positions. (a) Non-spot-month position limits. The position limits.... Notwithstanding the pre-existing exemption in non-spot months, a person must comply with spot month limits....

  5. Feline pyoderma therapy.

    PubMed

    Wildermuth, Brett E; Griffin, Craig E; Rosenkrantz, Wayne S

    2006-08-01

    Feline pyoderma is a disease entity more prevalent than previously described. Diagnosis is made by finding bacteria in the presence of inflammatory cells or bacterial phagocytosis on routine cytological examination. Diseases leading to secondary bacterial pyoderma include allergic and inflammatory skin diseases, parasitosis, feline chin acne, and others. Lesions of feline pyoderma are variable and include crusted and eroded papules, pustules, furuncles, eroded to ulcerated plaques with variable exudation and crusting, and linear to nodular ulcerative granulomatous lesions. Three cases of feline pyoderma responsive to antimicrobial therapy are discussed: case 1, a 10.5-year-old male neutered domestic short hair with eosinophilic lip ulcer, case 2, a 7-year-old male neutered domestic short hair with multiple cutaneous eosinophilic plaques, and case 3, an 8-month-old male neutered domestic short hair cat with Pseudomonas dermatitis, vasculitis, and panniculitis. Antibiotic selection for treatment of feline pyoderma should be based on cytological examination, and culture and sensitivity in unresponsive cases.

  6. Osteitis in the Course of Pyodema Gangrenosum. Case Raport.

    PubMed

    Kaźmierczak-Koćwin, Andrzej; Pieczyrak, Robert; Kusz, Damian; Kucharz, Eugeniusz; Kusz, Marcin

    2016-11-30

    We present the case of a male patient admitted to the Department of Orthopaedics and Musculoskeletal Traumatology, Medical University of Silesia (MUS) in Katowice, due to a right hindfoot abscess with calcaneal infiltration and pain in the forehead and the back, with evidence of local inflammation. The patient had a history of ulcerative colitis and sclerosing cholangitis was suspected. During the hospital stay, the patient underwent calcaneal CT, surgery (resection of an inflammatory focus) and MRI of the thoracic and lumbosacral spine, which revealed inflamed spinous processes of the Th10, Th11 and Th12 vertebrae. Numerous cultures and histo-pathological examinations were performed. Specialist consultations were obtained. The differential diagnosis included myeloproliferative and lymphoproliferative processes as well as skin and soft tissue neoplasms. The clinical presentation and examination results led to a diagnosis of pyoderma gangrenosum and the patient was referred to the Department of Internal Medicine and Rheumatology of the MUS to undergo further treatment.

  7. Increased Susceptibility to Chemical Toxicity with (Pre-existing ...

    EPA Pesticide Factsheets

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identified the type of information needed to evaluate the relationships of interest. This is for presentation at the 54th Society of Toxicology Annual Meeting and ToxExpo 2015.

  8. 43 CFR 3427.4 - Pre-existing consents.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Pre-existing consents. 3427.4 Section 3427.4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) COMPETITIVE LEASING Split Estate Leasing § 3427.4...

  9. 43 CFR 3427.4 - Pre-existing consents.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Pre-existing consents. 3427.4 Section 3427.4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) COMPETITIVE LEASING Split Estate Leasing § 3427.4...

  10. 43 CFR 3427.4 - Pre-existing consents.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Pre-existing consents. 3427.4 Section 3427.4 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) COMPETITIVE LEASING Split Estate Leasing § 3427.4...

  11. Increased Susceptibility to Chemical Toxicity with Pre-existing ...

    EPA Pesticide Factsheets

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identify the type of information needed to evaluate the relationships of interest. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which is also modulated by a particular chemical of interest. This biomarker may be a physiological, biochemical, or genetic indicator that corresponds to a phase of the disease process and may be an indicator of where an individual is on the continuum of disease or health status. The relationship between chemical exposure and a biomarker may then be used to predict how preexisting conditions may modify health risks of chemical exposures. Several case studies are explored to describe the toxic chemical, the clinical biomarker, the impacted disease and the evidence that the chemical enhances disease risk: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration ate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; Trichloroethylene/increased anti-nuclear antibody/autoimmunit

  12. Recognizing pyoderma: more difficult than it may seem.

    PubMed

    Gortel, Kinga

    2013-01-01

    Although bacterial pyoderma is among the most commonly encountered dermatologic conditions in dogs, some cases present diagnostic challenges even to experienced clinicians. This article presents several unusual manifestations of pyoderma, including bullous impetigo, superficial spreading pyoderma, mucocutaneous pyoderma, and post-grooming furunculosis. Conditions mimicking pyoderma, including juvenile cellulitis, immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis, and pemphigus foliaceus are also described. Diagnostic techniques used for diagnosing and characterizing pyoderma are also discussed.

  13. Travel to high altitude with pre-existing lung disease.

    PubMed

    Luks, A M; Swenson, E R

    2007-04-01

    The pathophysiology of high-altitude illnesses has been well studied in normal individuals, but little is known about the risks of high-altitude travel in patients with pre-existing lung disease. Although it would seem self-evident that any patient with lung disease might not do well at high altitude, the type and severity of disease will determine the likelihood of difficulty in a high-altitude environment. The present review examines whether these individuals are at risk of developing one of the main forms of acute or chronic high-altitude illness and whether the underlying lung disease itself will get worse at high elevations. Several groups of pulmonary disorders are considered, including obstructive, restrictive, vascular, control of ventilation, pleural and neuromuscular diseases. Attempts will be made to classify the risks faced by each of these groups at high altitude and to provide recommendations regarding evaluation prior to high-altitude travel, advice for or against taking such excursions, and effective prophylactic measures.

  14. Cutaneous microangiopathic thrombosis complicated by pyoderma gangrenosum in post-cardiac surgery heparin-induced thrombocytopaenia.

    PubMed

    Luthra, Suvitesh; Theodore, Sanjay; Liava'a, Matthew; Atkinson, Victoria; Tatoulis, James

    2009-08-01

    Thrombotic cutaneous gangrene is a rare complication of heparin-induced thrombocytopaenia after cardiac surgery. We report a case and discuss management issues with cardiopulmonary bypass for cardiac surgery in this condition.

  15. A case of perineal ecthyma gangrenosum

    PubMed Central

    Akkurt, Zeynep Meltem; Fidan, Veysi; Uçmak, Derya; Dal, Tuba; Kelekçi, Selvi; Uçak, Haydar

    2016-01-01

    Ecthyma gangrenosum is a skin lesion associated with Pseudomonas aeruginosa. A previously healthy one-year-old boy who had been diagnosed with varicella 10 days ago was admitted to our hospital with complaints of diarrhea, green ear discharge and new lesions in the diaper area. Intravenous meropenem and amikacin had been previously initiated. Physical examination revealed greenish, well bordered necrotic ulcers on both gluteal areas and the perianal area. Pseudomonas aeruginosa grew in wound culture. A colostomy was opened due to recalcitrant diarrhea and ulcers. The patient remitted in one month and was discharged. T lymphocyte subgroups and immunoglobulins were found to be normal on immunologic evaluation. We presented this case to draw attention to the fact that ecthyma gangrenosum due to Pseudomonas aeruginosa may occur in the diaper area and that sepsis due to Pseudomonas should be investigated. PMID:27103864

  16. [Ecthyma gangrenosum of the eyelid after chickenpox].

    PubMed

    Ouédraogo, M-S; Korsaga Somé, N; Tapsoba, G-P; Ouédraogo, A-N; Sondo, K-A; Inouss, I-A; Sanou, M-L; Konsem, T; Sakandé, J; Barro Traoré, F; Niamba, P; Traoré, A

    2016-10-01

    Ecthyma gangrenosum is an acute ulcer necrotic skin infection frequently caused by Pseudomonas aeruginosa. It is characterised by necrotic ulcerations circumscribed by an inflammatory halo. Lesions are normally found in the anal, genital and axillary regions. Ecthyma gangrenosum is most commonly seen in immunodepressed patients (cytotoxic chemotherapy, HIV infection, neutropenia or functional neutrophil deficiency, agammaglobulinemia). It is a rarely described complication in chicken pox. Herein we report the case of a girl aged 2 ½ years presenting in our dermatology department with ecthyma gangrenosum on the right upper eyelid secondary to varicella. The disease course was marked by fibrous scarring of the inner canthus with ptosis of the right upper eyelid. The retractile scarring caused disability. There have been previous reports of the contribution of non-steroidal anti- inflammatory drugs (NSAIDs) to the appearance of necrotic cutaneous super infections during the course of chickenpox. The occurrence of such complications on an eyelid may be harmful not only for the function of the eye but it can also cause extensive aesthetic impairment. Subsequent aesthetic and functional impairment may be improved by corrective surgery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Pyoderma Vegetans Misdiagnosed as Verrucous Carcinoma.

    PubMed

    Aksu Çerman, Aslı; Aktaş, Ezgi; Kıvanç Altunay, İlknur; Demirkesen, Cuyan

    2016-02-01

    Pyoderma vegetans, a rare disorder of the skin, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. It is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. Here, the authors report the case of a 33-year-old man who was misdiagnosed as having verrucous carcinoma for 4 years.

  18. A Double Whammy: Health Promotion Among Cancer Survivors with Pre-Existing Functional Limitations

    PubMed Central

    Volker, Deborah L.; Becker, Heather; Kang, Sook Jung; Kullberg, Vicki

    2012-01-01

    Purpose/Objectives To explore the experience of living with a cancer diagnosis within the context of a pre-existing functional disability and to identify strategies to promote health in this growing population of cancer survivors. Research Approach Qualitative descriptive Setting Four sites in the United States Participants 19 female cancer survivors with pre-existing disabling conditions Methodologic Approach Four focus groups were conducted. The audiotapes were transcribed and analyzed using content analysis techniques. Main Research Variables cancer survivor, disability, health promotion Findings Analytic categories included living with a cancer diagnosis, health promotion strategies, and wellness program development for survivors with pre-existing functional limitations. Participants described many challenges associated with managing a cancer diagnosis on top of living with a chronic disabling functional limitation. They identified strategies they used to maintain their health and topics to be included in health promotion programs tailored for this unique group of cancer survivors. Conclusions The “double whammy” of a cancer diagnosis for persons with pre-existing functional limitations requires modification of health promotion strategies and programs to promote wellness in this group of cancer survivors. Interpretation Nurses and other health care providers must attend to patients’ pre-existing conditions as well as the challenges of the physical, emotional, social, and economic sequelae of a cancer diagnosis. PMID:23269771

  19. Pre-existence and emergence of drug resistance in HIV-1 infection.

    PubMed Central

    Bonhoeffer, S; Nowak, M A

    1997-01-01

    Antiviral treatment of HIV-1 infection often fails because of the rapid emergence of resistant virus within weeks of the start of therapy. This raises the question of whether resistant viruses pre-exist in drug-naive patients or whether it is produced after the start of therapy. Here we compare the likelihood of pre-existence with the likelihood of production of resistant virus during therapy. We show that provided resistant virus pre-exists, then a stronger therapy may lead to a greater initial reduction of virus load, but will also cause a faster rise of resistant virus. In this case the total benefit of treatment is independent of the degree of inhibition of sensitive virus. If, on the other hand, resistant mutants do not pre-exist, then the emergence of resistance during treatment depends on the efficacy of the drug. If the drug is sufficiently potent to eradicate sensitive virus, then the probability that resistant mutants first appear during therapy is smaller than the probability that they existed before therapy. If the drug cannot eradicate the sensitive virus, then after sufficiently long time resistant mutants will appear. However, mutants that are unlikely to pre-exist may taken long time to appear. PMID:9178534

  20. Ecthyma gangrenosum in a patient with toxic epidermal necrolysis.

    PubMed

    Downey, Douglas M; O'Bryan, Meghan C; Burdette, Steve D; Michael, Johnson R; Saxe, Jonathan M

    2007-01-01

    Toxic epidermal necrolysis and Stevens-Johnson syndrome are a spectrum of disease characterized by a delayed hypersensitivity reaction that involves the skin and mucous membranes and typically is associated with either recent upper respiratory infection or with certain medications. Ecthyma gangrenosum is a rare necrotizing vasculitis that most commonly affects immunocompromised and burn patients and is often a sequela of Pseudomonas aeruginosa bacteremia. The cutaneous lesions of ecthyma gangrenosum are characterized by an erythematous halo surrounding a dark gray or black nodule. P. aeruginosa preferentially invades the venules, resulting in secondary thrombosis of the arterioles, tissue edema, and separation of the epidermis. Management of ecthyma gangrenosum includes systemic treatment with antipseudomonal antibiotics and débridment of the lesions, as well as improving the patient's immune status if possible. We present a case of a patient admitted to the burn unit for toxic epidermal necrolysis who developed pseudomonal bacteremia with ecthyma gangrenosum.

  1. Pre-existing biotherapeutic-reactive antibodies: survey results within the American Association of Pharmaceutical Scientists.

    PubMed

    Xue, Li; Fiscella, Michele; Rajadhyaksha, Manoj; Goyal, Jaya; Holland, Claire; Gorovits, Boris; Morimoto, Alyssa

    2013-07-01

    The immunogenicity profile of a biotherapeutic is determined by a multitude of product and patient-related risk factors that can influence the observed incidence and clinical consequences of immunogenicity. Pre-existing antibodies, i.e., biotherapeutic-reactive antibodies present in samples from treatment-naïve subjects, have been commonly observed during immunogenicity assessments; however their relevance in terms of the safety and efficacy of a biotherapeutic is poorly understood. An American Association of Pharmaceutical Scientists-sponsored survey was conducted to gather information about the prevalence, nature, and consequences of pre-existing antibodies in clinical and nonclinical studies. The survey results indicate that pre-existing antibodies against a variety of biotherapeutics (e.g., mAbs, fusion proteins) are frequently encountered, especially in the context of autoimmune diseases, but that the methods and approaches used to detect, characterize, and report these antibodies vary. In most cases, pre-existing antibodies did not appear to have clinical consequences; however, a few of the respondents reported having observed an effect on pharmacokinetic, pharmacodynamic, safety, and/or efficacy parameters. The findings from this survey are an important first step in evaluating the potential risks associated with the presence of pre-existing antibodies and highlight the importance of standardizing the approaches for detection and characterization of these antibodies. Cross-industry sharing of case studies and relevant data collection will help better inform biotherapeutic risk/benefit profiles and provide deeper understanding of the biological consequences of pre-existing antibodies.

  2. Pediatric blood sample collection from a pre-existing peripheral intravenous (PIV) catheter.

    PubMed

    Braniff, Heather; DeCarlo, Ann; Haskamp, Amy Corey; Broome, Marion E

    2014-01-01

    Aiming to minimize pain in a hospitalized child, the purpose of this observational study was to describe characteristics of blood samples collected from pre-existing peripheral intravenous (PIV) catheters in pediatric patients. One hundred and fifty blood samples were reviewed for number of unusable samples requiring a specimen to be re-drawn. Success of the blood draw and prevalence of the loss of the PIV following blood collection was also measured. Findings included one clotted specimen, success rate of 91.3%, and 1.3% of PIVs becoming non-functional after collection. Obtaining blood specimens from a pre-existing PIV should be considered in a pediatric patient.

  3. TDE fallback cut-off due to a pre-existing accretion disc

    NASA Astrophysics Data System (ADS)

    Kathirgamaraju, Adithan; Barniol Duran, Rodolfo; Giannios, Dimitrios

    2017-07-01

    Numerous tidal disruption event (TDE) candidates originating from galactic centres have been detected (e.g. by Swift and ASASSN). Some of their host galaxies show typical characteristics of a weak active galactic nucleus (AGN), indicative of a pre-existing accretion disc around the supermassive black hole (SMBH). In this work, we develop an analytic model to study how a pre-existing accretion disc affects a TDE. We assume the density of the disc ρ ∝ R-λ, R being the radial distance from the SMBH and λ varying between 0.5 and 1.5. Interactions between the pre-existing accretion disc and the stream of the tidally disrupted star can stall the stream far from the SMBH, causing a sudden drop in the rate of fallback of gas into the SMBH. These interactions could explain the steep cut-off observed in the light curve of some TDE candidates (e.g. Swift J1644 and Swift J2058). With our model, it is possible to use the time of this cut-off to constrain some properties pertaining to the pre-existing accretion disc, such as λ and the disc viscosity parameter α. We demonstrate this by applying our theory to the TDE candidates Swift J1644, Swift J2058 and ASASSN-14li. Our analysis favours a disc profile with λ ˜ 1 for viscosity parameters α ˜ 0.01-0.1.

  4. Are There Pre-Existing Neural, Cognitive, or Motoric Markers for Musical Ability?

    ERIC Educational Resources Information Center

    Norton, Andrea; Winner, Ellen; Cronin, Karl; Overy, Katie; Lee, Dennis J.; Schlaug, Gottfried

    2005-01-01

    Adult musician's brains show structural enlargements, but it is not known whether these are inborn or a consequence of long-term training. In addition, music training in childhood has been shown to have positive effects on visual-spatial and verbal outcomes. However, it is not known whether pre-existing advantages in these skills are found in…

  5. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross Estate...

  6. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross Estate...

  7. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross Estate...

  8. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross Estate...

  9. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross Estate...

  10. Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting.

    PubMed

    Velazquez, Victoria M; Meadows, Aaron S; Pineda, Ricardo J; Camboni, Marybeth; McCarty, Douglas M; Fu, Haiyan

    2017-03-17

    Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment. The rapamycin plus prednisolone treatment resulted in significant decreases in the frequency of B cells, plasma cells, and IgG-secreting and AAV9-specific Ab-producing plasma cells in bone marrow. The rapamycin plus prednisolone treatment also significantly reduced frequencies of IgD(-)IgG(+) class-switched/FAS(+)CL7(+) germinal center B cells, and of activated CD4(+) T cells expressing PD1 and GL7, in spleen. These data suggest that rapamycin plus prednisolone has selective inhibitory effects on both T helper type 2 support of B cell activation in spleen and on bone marrow plasma cell survival, leading to effective AAV9 Abs depletion. This promising immunomodulation approach is highly translatable, and it poses minimal risk in the context of therapeutic benefits promised by gene therapy for severe monogenetic diseases, with a single or possibly a few treatments over a lifetime.

  11. Contributions Made by a Strengths-Oriented Intervention to Trusting Relationships within Pre-Existing Teams

    ERIC Educational Resources Information Center

    King, W. Bernt

    2012-01-01

    This qualitative study spotlighted a grounded theory regarding contributions to affect- and cognition-based trust by a strengths-oriented intervention in pre-existing teams. Using purposeful and convenience sampling, 18 participants in a strengths-oriented intervention from 2 different regions of the Pacific Northwest were selected. A…

  12. Overcoming pre-existing adenovirus immunity by genetic engineering of adenovirus-based vectors.

    PubMed

    Seregin, Sergey S; Amalfitano, Andrea

    2009-12-01

    Adenovirus (Ad)-based vectors offer several benefits showing their potential for use in a variety of vaccine applications. Recombinant Ad-based vaccines possess potent immunogenic potential, capable of generating humoral and cellular immune responses to a variety of pathogen-specific antigens expressed by the vectors. Ad5 vectors can be readily produced, allowing for usage in thousands of clinical trial subjects. This is now coupled with a history of safe clinical use in the vaccine setting. However, traditional Ad5-based vaccines may not be generating optimal antigen-specific immune responses, and generate diminished antigen-specific immune responses when pre-existing Ad5 immunity is present. These limitations have driven initiation of several approaches to improve the efficacy of Ad-based vaccines, and/or allow modified vaccines to overcome pre-existing Ad immunity. These include: generation of chemically modified Ad5 capsids; generation of chimeric Ads; complete replacement of Ad5-based vaccine platforms with alternative (human and non-human origin) Ad serotypes, and Ad5 genome modification approaches that attempt to retain the native Ad5 capsid, while simultaneously improving the efficacy of the platform as well as minimizing the effect of pre-existing Ad immunity. Here we discuss recent advances in- and limitations of each of these approaches, relative to their abilities to overcome pre-existing Ad immunity.

  13. Are There Pre-Existing Neural, Cognitive, or Motoric Markers for Musical Ability?

    ERIC Educational Resources Information Center

    Norton, Andrea; Winner, Ellen; Cronin, Karl; Overy, Katie; Lee, Dennis J.; Schlaug, Gottfried

    2005-01-01

    Adult musician's brains show structural enlargements, but it is not known whether these are inborn or a consequence of long-term training. In addition, music training in childhood has been shown to have positive effects on visual-spatial and verbal outcomes. However, it is not known whether pre-existing advantages in these skills are found in…

  14. An Exploratory Examination of Students' Pre-Existing Beliefs about Leadership

    ERIC Educational Resources Information Center

    Caza, Arran; Rosch, David M.

    2014-01-01

    Preparing future leaders is a long-standing priority in higher education, but doubts have been raised about whether this goal is being achieved. Pedagogical research suggests that leadership development can be improved by taking account of students' pre-existing beliefs about leadership; however, little is currently known about those beliefs. To…

  15. Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

    ERIC Educational Resources Information Center

    Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

    2011-01-01

    The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

  16. Pyoderma vegetans developed on chronic leg ulcer.

    PubMed

    Molodoi, Andreea Dana; Dimitriu, Andreea; Andronic, Cătălina Diana; Stoleriu, Gabriela; Bădescu, Aida; Boda, D; Brănisteanu, Daciana Elena

    2015-01-01

    Pyoderma vegetans is a rare disorder that more commonly affects middle-aged persons, with a male predilection. It is characterized by vegetating lesions that coalescence into a plaque with eroded surface, covered by purulent discharge and crusts. The etiology of this disease is not known with certainty, but it is often associated with bacterial infections in immunocompromised patients. We report the case of a 73-year-old men who presented to the Iasi Dermatology Clinic with a large, irregular, relatively well-defined dermohypodermic ulcer, with infiltrated sclerosing borders, accompanied by pain, with the floor covered in the Northern part by a proliferative, vegetative bleeding area, and the rest by a yellowish secretion and cellular debris, located on the left leg. Bacteriological examination of ulcer secretion identified Pseudomonas aeruginosa. Anatomopathological examination confirmed the development of Pyoderma vegetans on chronic leg ulcer. Under specific treatment for chronic leg ulcer and eradication of infectious focus the outcome was favorable both in terms of trophic ulcer scar- ring and Pyoderma vegetans healing.

  17. An unusual presentation of blastomycosislike pyoderma (pyoderma vegetans) and a review of the literature.

    PubMed

    Cerullo, Lauren; Zussman, Jamie; Young, Lorraine

    2009-10-01

    We report a case of blastomycosislike pyoderma (BLP), also known as pyoderma vegetans, in a 75-year-old woman. The patient initially presented with multiple lesions, some classic and others with highly uncharacteristic morphology. The appearance of unusual purulent hornlike lesions on both cheeks delayed recognition of the disease. The diagnosis of BLP is contingent on the fulfillment of 6 diagnostic criteria and the disease is highly refractory to current treatment strategies. We review the present understanding of disease pathology and available therapeutic modalities.

  18. Interaction of ascending magma with pre-existing crustal structures: Insights from analogue modeling

    NASA Astrophysics Data System (ADS)

    Le Corvec, N.; Menand, T.; Rowland, J. V.

    2010-12-01

    Magma transport through dikes is a major component of the development of basaltic volcanic fields. Basaltic volcanic fields occur in many different tectonic setting, from tensile (e.g., Camargo Volcanic Field, Mexico) to compressive (e.g., Abu Monogenetic Volcano Group, Japan). However, an important observation is that, independently of their tectonic setting, volcanic fields are characterized by numerous volcanic centers showing clustering and lineaments, each volcanic center typically resulting from a single main eruption. Analyses from Auckland Volcanic Field reveal that, for each eruption, magma was transported from its source and reached the surface at different places within the same field, which raises the important question of the relative importance of 1) the self-propagation of magma through pristine rock, as opposed to 2) the control exerted by pre-existing structures. These two mechanisms have different implications for the alignment of volcanic centers in a field as these may reflect either 1) the state of crustal stress dikes would have experienced (with a tendency to propagate perpendicular to the least compressive stress) or 2) the interaction of propagating dikes with pre-existing crustal faults. In the latter case, lineaments might not be related to the syn-emplacement state of stress of the crust. To address this issue, we have carried out a series of analogue experiments in order to constrain the interaction of a propagating magma-filled dike with superficial pre-existing structures (e.g., fracture, fault, joint system). The experiments involved the injection of air (a buoyant magma analogue) into elastic gelatine solids (crustal rock analogues). Cracks were cut into the upper part of the gelatine solids prior to the injection of air to simulate the presence of pre-existing fractures. The volume of the propagating dikes, their distance from pre-existing fractures and the ambient stress field were systematically varied to assess their influence

  19. Normal fault growth above pre-existing structures: insights from discrete element modelling

    NASA Astrophysics Data System (ADS)

    Wrona, Thilo; Finch, Emma; Bell, Rebecca; Jackson, Christopher; Gawthorpe, Robert; Phillips, Thomas

    2016-04-01

    In extensional systems, pre-existing structures such as shear zones may affect the growth, geometry and location of normal faults. Recent seismic reflection-based observations from the North Sea suggest that shear zones not only localise deformation in the host rock, but also in the overlying sedimentary succession. While pre-existing weaknesses are known to localise deformation in the host rock, their effect on deformation in the overlying succession is less well understood. Here, we use 3-D discrete element modelling to determine if and how kilometre-scale shear zones affect normal fault growth in the overlying succession. Discrete element models use a large number of interacting particles to describe the dynamic evolution of complex systems. The technique has therefore been applied to describe fault and fracture growth in a variety of geological settings. We model normal faulting by extending a 60×60×30 km crustal rift-basin model including brittle and ductile interactions and gravitation and isostatic forces by 30%. An inclined plane of weakness which represents a pre-existing shear zone is introduced in the lower section of the upper brittle layer at the start of the experiment. The length, width, orientation and dip of the weak zone are systematically varied between experiments to test how these parameters control the geometric and kinematic development of overlying normal fault systems. Consistent with our seismic reflection-based observations, our results show that strain is indeed localised in and above these weak zones. In the lower brittle layer, normal faults nucleate, as expected, within the zone of weakness and control the initiation and propagation of neighbouring faults. Above this, normal faults nucleate throughout the overlying strata where their orientations are strongly influenced by the underlying zone of weakness. These results challenge the notion that overburden normal faults simply form due to reactivation and upwards propagation of pre-existing

  20. Pre-existing immunity against vaccine vectors – friend or foe?

    PubMed Central

    Saxena, Manvendra; Van, Thi Thu Hao; Baird, Fiona J.; Coloe, Peter J.

    2013-01-01

    Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses. PMID:23175507

  1. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis.

    PubMed

    Maeda, Osamu; Yokota, Kenji; Atsuta, Naoki; Katsuno, Masahisa; Akiyama, Masashi; Ando, Yuichi

    2016-02-01

    A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase elevation appeared after two doses of nivolumab, and the treatment was postponed until it improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial muscle weakness which were consistent with an acute exacerbation of MG, and the symptoms relieved without additional treatment for MG. He achieved shrinkage of metastasis after ten doses of nivolumab. Although a case who died due to MG after administration of nivolumab was reported recently, pre-existing MG is considered not to be always a contraindication of nivolumab.

  2. Are there pre-existing neural, cognitive, or motoric markers for musical ability?

    PubMed

    Norton, Andrea; Winner, Ellen; Cronin, Karl; Overy, Katie; Lee, Dennis J; Schlaug, Gottfried

    2005-11-01

    Adult musician's brains show structural enlargements, but it is not known whether these are inborn or a consequence of long-term training. In addition, music training in childhood has been shown to have positive effects on visual-spatial and verbal outcomes. However, it is not known whether pre-existing advantages in these skills are found in children who choose to study a musical instrument nor is it known whether there are pre-existing associations between music and any of these outcome measures that could help explain the training effects. To answer these questions, we compared 5- to 7-year-olds beginning piano or string lessons (n=39) with 5- to 7-year-olds not beginning instrumental training (n=31). All children received a series of tests (visual-spatial, non-verbal reasoning, verbal, motor, and musical) and underwent magnetic resonance imaging. We found no pre-existing neural, cognitive, motor, or musical differences between groups and no correlations (after correction for multiple analyses) between music perceptual skills and any brain or visual-spatial measures. However, correlations were found between music perceptual skills and both non-verbal reasoning and phonemic awareness. Such pre-existing correlations suggest similarities in auditory and visual pattern recognition as well a sharing of the neural substrates for language and music processing, most likely due to innate abilities or implicit learning during early development. This baseline study lays the groundwork for an ongoing longitudinal study addressing the effects of intensive musical training on brain and cognitive development, and making it possible to look retroactively at the brain and cognitive development of those children who emerge showing exceptional musical talent.

  3. Discrete modeling of hydraulic fracturing processes in a complex pre-existing fracture network

    NASA Astrophysics Data System (ADS)

    Kim, K.; Rutqvist, J.; Nakagawa, S.; Houseworth, J. E.; Birkholzer, J. T.

    2015-12-01

    Hydraulic fracturing and stimulation of fracture networks are widely used by the energy industry (e.g., shale gas extraction, enhanced geothermal systems) to increase permeability of geological formations. Numerous analytical and numerical models have been developed to help understand and predict the behavior of hydraulically induced fractures. However, many existing models assume simple fracturing scenarios with highly idealized fracture geometries (e.g., propagation of a single fracture with assumed shapes in a homogeneous medium). Modeling hydraulic fracture propagation in the presence of natural fractures and homogeneities can be very challenging because of the complex interactions between fluid, rock matrix, and rock interfaces, as well as the interactions between propagating fractures and pre-existing natural fractures. In this study, the TOUGH-RBSN code for coupled hydro-mechanical modeling is utilized to simulate hydraulic fracture propagation and its interaction with pre-existing fracture networks. The simulation tool combines TOUGH2, a simulator of subsurface multiphase flow and mass transport based on the finite volume approach, with the implementation of a lattice modeling approach for geomechanical and fracture-damage behavior, named Rigid-Body-Spring Network (RBSN). The discrete fracture network (DFN) approach is facilitated in the Voronoi discretization via a fully automated modeling procedure. The numerical program is verified through a simple simulation for single fracture propagation, in which the resulting fracture geometry is compared to an analytical solution for given fracture length and aperture. Subsequently, predictive simulations are conducted for planned laboratory experiments using rock-analogue (soda-lime glass) samples containing a designed, pre-existing fracture network. The results of a preliminary simulation demonstrate selective fracturing and fluid infiltration along the pre-existing fractures, with additional fracturing in part

  4. Numerical Modelling of Extended Leak-Off Test with a Pre-Existing Fracture

    NASA Astrophysics Data System (ADS)

    Lavrov, A.; Larsen, I.; Bauer, A.

    2016-04-01

    Extended leak-off test (XLOT) is one of the few techniques available for stress measurements in oil and gas wells. Interpretation of the test is often difficult since the results depend on a multitude of factors, including the presence of natural or drilling-induced fractures in the near-well area. Coupled numerical modelling of XLOT has been performed to investigate the pressure behaviour during the flowback phase as well as the effect of a pre-existing fracture on the test results in a low-permeability formation. Essential features of XLOT known from field measurements are captured by the model, including the saw-tooth shape of the pressure vs injected volume curve, and the change of slope in the pressure vs time curve during flowback used by operators as an indicator of the bottomhole pressure reaching the minimum in situ stress. Simulations with a pre-existing fracture running from the borehole wall in the radial direction have revealed that the results of XLOT are quite sensitive to the orientation of the pre-existing fracture. In particular, the fracture initiation pressure and the formation breakdown pressure increase steadily with decreasing angle between the fracture and the minimum in situ stress. Our findings seem to invalidate the use of the fracture initiation pressure and the formation breakdown pressure for stress measurements or rock strength evaluation purposes.

  5. TheQ1 Influence of Innate and Pre-Existing Immunity on Adenovirus Therapy

    PubMed Central

    Zaiss, Anne K.; Machado, Hidevaldo B.; Herschman, Harvey R.

    2010-01-01

    Recombinant adenovirus serotype 5 (Ad5) vectors have been studied extensively in preclinical gene therapy models and in a range of clinical trials. However, innate immune responses to adenovirus vectors limit effectiveness of Ad5 based therapies. Moreover, extensive pre-existing Ad5 immunity in human populations will likely limit the clinical utility of adenovirus vectors, unless methods to circumvent neutralizing antibodies that bind virus and block target cell transduction can be developed; Furthermore, memory T cell and humoral responses to Ad5 are associated with increased toxicity, raising safety concerns for therapeutic adenovirus vectors in immunized hosts. Most preclinical studies have been performed in naïve animals; although pre-existing immunity is among the greatest hurdles for adenovirus therapies, it is also one of the most neglected experimentally. Here we summarize findings using adenovirus vectors in naïve animals, in Ad-immunized animals and in clinical trials, and review strategies proposed to overcome innate immune responses and pre-existing immunity. PMID:19711370

  6. Pregnant women with pre-existing diabetes: family support in managing the pregnancy process.

    PubMed

    Letherby, Gayle; Stephen, Nicole; Stenhouse, Elizabeth

    2012-12-01

    In this paper, we report on findings from a Diabetes UK funded qualitative research project concerned to explore daughter/mother relationships during pregnancy and the transition to motherhood of women with pre-existing diabetes. In-depth qualitative interviews took place with 12 pregnant women with pre-existing diabetes and four of their mothers, three (male) partners and one father. The study was exploratory in nature and aimed to consider what support pregnant women felt they needed and what support they received from their mothers and other family members to discover policy and practice needs and identify further research concerns. Here, we focus on one theme from the data: management of the pregnancy process from planning for pregnancy and through pregnancy with specific reference to relationships with family members. Respondents reflect on the relationship between diabetes and pregnancy planning, on managing pregnancy and on their relationships with healthcare professionals. The data suggest overwhelmingly that pre-existing diabetes is a significant aspect of pregnancy planning and pregnancy for women and that managing the pregnancy process is a more positive experience if they have the support of family members.

  7. Sport climbing with pre-existing cardio-pulmonary medical conditions.

    PubMed

    Kuepper, T; Morrison, A; Gieseler, U; Schoeffl, V

    2009-06-01

    Over the past 25 years sport climbing has developed from an elite extreme sport subculture pursued by few into a mainstream recreational sport enjoyed globally by climbers of all ages, climbing abilities, and with pre-existing health conditions. As the demands and grades of climbing difficulty have increased over this period, most scientific literature on sport climbing focused on acute injuries and overuse syndromes, or performance physiology in healthy adult males. The physiological response to sport climbing is more similar to that of resistance training (i.e., body building) rather than a predominantly aerobic sport (i.e., running, cycling), so that heart rate and blood pressure during a climb will be disproportionately high relative to the 'exercise' of climbing, and breathing may be irregular. Therefore this review sought evidence-based recommendations for recreational sport climbing participation by those individuals with pre-existing cardiopulmonary medical conditions including coronary heart disease, chronic heart failure, cardiac dysrhythmia, pulmonary diseases (i.e., asthma) or hypertension. This review defines the criteria that must be fulfilled for safe sport climbing by those with pre-existing cardiopulmonary conditions or those with hypertension.

  8. Pre-existing lumbar spine diagnosis as a predictor of outcomes in National Football League athletes.

    PubMed

    Schroeder, Gregory D; Lynch, T Sean; Gibbs, Daniel B; Chow, Ian; LaBelle, Mark; Patel, Alpesh A; Savage, Jason W; Hsu, Wellington K; Nuber, Gordon W

    2015-04-01

    It is currently unknown how pre-existing lumbar spine conditions may affect the medical evaluation, draft status, and subsequent career performance of National Football League (NFL) players. To determine if a pre-existing lumbar diagnosis affects a player's draft status or his performance and longevity in the NFL. Cohort study; Level 3. The investigators evaluated the written medical evaluations and imaging reports of prospective NFL players from a single franchise during the NFL Scouting Combine from 2003 to 2011. Players with a reported lumbar spine diagnosis and with appropriate imaging were included in this study. Athletes were then matched to control draftees without a lumbar spine diagnosis by age, position, year, and round drafted. Career statistics and performance scores were calculated. Of a total of 2965 athletes evaluated, 414 were identified as having a pre-existing lumbar spine diagnosis. Players without a lumbar spine diagnosis were more likely to be drafted than were those with a diagnosis (80.2% vs. 61.1%, respectively, P < .001). Drafted athletes with pre-existing lumbar spine injuries had a decrease in the number of years played compared with the matched control group (4.0 vs. 4.3 years, respectively, P = .001), games played (46.5 vs. 50.8, respectively, P = .0001), and games started (28.1 vs. 30.6, respectively, P = .02) but not performance score (1.4 vs. 1.8, respectively, P = .13). Compared with controls, players were less likely to be drafted if they had been diagnosed with spondylosis (62.37% vs. 78.55%), a lumbar herniated disc (60.27% vs. 78.43%), or spondylolysis with or without spondylolisthesis (64.44% vs. 78.15%) (P < .001 for all), but there was no appreciable effect on career performance; however, the diagnosis of spondylolysis was associated with a decrease in career longevity (P < .05). Notably, 2 athletes who had undergone posterior lateral lumbar fusion were drafted. One played in 125 games, and the other is still active and has

  9. Fadeout in an Early Mathematics Intervention: Constraining Content or Pre-existing Differences?

    PubMed Central

    Bailey, Drew H.; Nguyen, Tutrang; Jenkins, Jade Marcus; Domina, Thurston; Clements, Douglas H.; Sarama, Julie S.

    2016-01-01

    A robust finding across research on early childhood educational interventions is that the treatment effect diminishes over time, with children not receiving the intervention eventually catching up to children who did. One popular explanation for fadeout of early mathematics interventions is that elementary school teachers may not teach the kind of advanced content that children are prepared for after receiving the intervention, so lower-achieving children in the control groups of early mathematics interventions catch up to the higher-achieving children in the treatment groups. An alternative explanation is that persistent individual differences in children’s long-term mathematical development result more from relatively stable pre-existing differences in their skills and environments than from the direct effects of previous knowledge on later knowledge. We tested these two hypotheses using data from an effective preschool mathematics intervention previously known to show a diminishing treatment effect over time. We compared the intervention group to a matched subset of the control group with a similar mean and variance of scores at the end of treatment. We then tested the relative contributions of factors that similarly constrain learning in children from treatment and control groups with the same level of post-treatment achievement and pre-existing differences between these two groups to the fadeout of the treatment effect over time. We found approximately 72% of the fadeout effect to be attributable to pre-existing differences between children in treatment and control groups with the same level of achievement at post-test. These differences were fully statistically attenuated by children’s prior academic achievement. PMID:27505700

  10. Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques.

    PubMed

    Greig, Jenny A; Calcedo, Roberto; Grant, Rebecca L; Peng, Hui; Medina-Jaszek, C Angelica; Ahonkhai, Omua; Qin, Qiuyue; Roy, Soumitra; Tretiakova, Anna P; Wilson, James M

    2016-12-07

    The seroprevalence of neutralizing antibodies (NAbs) to adeno-associated viral (AAV) vector capsids may preclude a percentage of the population from receiving gene therapy, particularly following systemic vector administration. We hypothesized that the use of intramuscular (IM) administration of AAV vectors might circumvent this issue. IM injections were used to administer AAV8 vectors expressing either secreted or non-secreted transgenes into mice and the influence of NAbs supplied by pre-administration of pooled human IgG on transgene expression was evaluated. We then studied the impact of naturally occurring pre-existing AAV8 NAbs on expression of a secreted transgene following IM vector delivery in rhesus macaques. Finally, we evaluated the ability to readminister AAV vectors via IM injections in rhesus macaques. In mice, the presence of AAV8 NAbs had no effect on gene expression in the injected skeletal muscle. However, liver transgene expression following hepatic distribution of the vector was ablated. In rhesus macaques, naturally occurring pre-existing AAV8 NAb titers of ⩽1:160 had no effect on expression levels of a secreted transgene after IM delivery of the vector. Additionally, readministration of AAV vectors was possible by IM injection into the previously injected muscle groups, with no effect on transgene expression by the original vector. Therefore, the presence of pre-existing NAbs in the human population should not preclude subjects from receiving gene therapy by IM administration of the vector so long as sufficient levels of secreted transgene expression can be produced without the involvement of liver.

  11. Effects of Injected Fluids on Pre-existing Faults observed from Surface and Downhole Seismic Arrays

    NASA Astrophysics Data System (ADS)

    Tang, Y.; Niu, F.; Chen, H.; Zuo, Q.

    2016-12-01

    Hydraulic fracturing is the key stimulation technology to improve unconventional hydrocarbon recovery. It involves pumping high-pressure fluid into reservoir rocks to force the opening of cracks, which could allow oil and gas to flow freely. The effects of injected fluids and associated stress changes on pre-existing faults must be monitored carefully to avoid undesirable ruptures. We deployed a small-scale seismic array consisting of 22 broadband seismographs at the surface and 20 downhole seismographs to study the dynamic processes involved in hydraulic fracturing. The simultaneous monitoring of surface and downhole seismic array could increase the detectability of microseismic events and enhance location accuracy. The downhole seismic array detected a total of 7270 microseismic events and 961 events were recorded by surface seismic array with high signal-to-noise ratios (SNRs). We found that induced seismicity occurred during and after the fluid injection with large spatial variations. This is also true to the inverted focal mechanisms. We noticed that several clusters of events are located >1 km away from the perforation shots such that their occurrence seems to have no direct involvement of the inject fluid. More likely they seem to be triggered slips on pre-existing faults. The pre-existing faults were reactivated by the injection of the early stages, and the triggered seismicity continued during the later operation regardless whether there is inflow of the fluid injected by the later stages. Overall, the "dry" triggered remote seismicity seems to have a higher average magnitude and a lower b-value in comparison with the "wet" inducted seismicity around the perforation shots.

  12. Tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension.

    PubMed

    Nabhan, Ashraf F; Elsedawy, Maged M

    2011-07-06

    The question of the target blood pressure in pregnant women with mild-moderate hypertension continues to be an area of debate. To compare tight versus very tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension for improving outcomes We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), CENTRAL (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to March 2011), and the metaRegister of Controlled Trials (31 March 2011). We handsearched citation lists of relevant publications, review articles, and included studies. Randomized controlled trials of tight versus very tight control in pregnant women with mild or moderate pre-existing or non-proteinuric gestational hypertension. Two authors independently assessed trial quality and extracted data. We expressed results as risk ratio (RR) or mean differences, together with their 95% confidence intervals (CI). We included two studies (256 participants) with mild-moderate pre-existing or non-proteinuric gestational hypertension. There was no evidence of a difference between tight and very tight control groups regarding severe pre-eclampsia (risk ratio (RR) 1.28, 95% CI 0.97 to 1.70; two trials, 256 participants). More women in the tight group were hospitalized during their pregnancy (RR 2.53, 95% CI 1.14 to 5.63; one trial, 125 participants). There was no evidence of a difference in other outcome measures including fetal distress, IUGR, neonatal admission to a NICU, perinatal deaths, induction of labor and cesarean delivery between the tight and the very tight control groups. Gestational age at delivery had a non-significant mean difference (MD) of -0.15 weeks between the tight and very tight control groups (MD -0.15, 95% CI -1.52 to 1.21, random-effects, T² = 0.75, I² = 77%; two trials, 256 participants). The MD in birthweight between the tight and the very tight control group was not significant (MD -100.00 grams, 95% CI -363.69 to 163.69; one

  13. Exacerbation of pre-existing diabetes insipidus during pregnancy, mechanisms and management.

    PubMed

    Tack, Lloyd J W; T'Sjoen, Guy; Lapauw, Bruno

    2017-06-01

    During pregnancy, physiological changes in osmotic homeostasis cause water retention. If excessive, this can cause gestational diabetes insipidus (DI), particularly in patients with already impaired vasopressin secretion. We present the case of a 34-year-old patient with pre-existing hypopituitarism who experienced a transient exacerbation of her DI during a twin pregnancy. In contrast to typical gestational DI, polyuria and polydipsia occurred during the first trimester and remained stable thereafter. This case highlights a challenging clinical entity of which pathophysiology, diagnostic approach and treatment will be discussed.

  14. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of.... B Appendix B to Part 434—Baseline Determination and Compliance Monitoring for Pre-existing... monthly (single-observation) procedure and an annual procedure shall be applied, as described below. b....

  15. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or vision...

  16. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or vision...

  17. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or vision...

  18. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or vision...

  19. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or...

  20. Ionization-induced annealing of pre-existing defects in silicon carbide

    NASA Astrophysics Data System (ADS)

    Zhang, Yanwen; Sachan, Ritesh; Pakarinen, Olli H.; Chisholm, Matthew F.; Liu, Peng; Xue, Haizhou; Weber, William J.

    2015-08-01

    A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments.

  1. Ionization-induced annealing of pre-existing defects in silicon carbide

    PubMed Central

    Zhang, Yanwen; Sachan, Ritesh; Pakarinen, Olli H.; Chisholm, Matthew F.; Liu, Peng; Xue, Haizhou; Weber, William J.

    2015-01-01

    A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments. PMID:26264864

  2. Deterioration of pre-existing hemiparesis due to injury of the ipsilateral anterior corticospinal tract.

    PubMed

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2013-05-29

    The anterior corticospinal tract (CST) has been suggested as one of the ipsilateral motor pathways, which contribute to motor recovery following stroke. In this study, we report on a patient who showed deterioration of pre-existing hemiparesis due to an injury of the ipsilateral anterior CST following a pontine infarct, as evaluated by diffusion tensor tractography (DTT). A 55-year-old male patient showed quadriparesis after the onset of an infarct in the right pontine basis. He had history of an infarct in the left middle cerebral artery territory 7 years ago. Consequently, he showed right hemiparesis before onset of the right pontine infarct. Following this, his right hemiparesis deteriorated whereas his left hemiparesis newly developed. The DTTs for whole CST of the right hemisphere in the patient and both hemispheres in control subjects descended through the known CST pathway. By contrast, the DTT for the left whole CST of the patient showed a complete injury finding. The DTTs for the anterior CST of control subjects passed through the known pathway of the CST from cerebral cortex to medulla and terminated in the anterior funiculus of the upper cervical cord. However, the DTT for right anterior CST in the patient showed discontinuation below the right pontine infarct. It appeared that the deterioration of the pre-existing right hemiparesis was ascribed to an injury of the right anterior CST due to the right pontine infarct.

  3. Pre-existing antidepressants and the outcome of group cognitive behaviour therapy for social phobia.

    PubMed

    Rosser, Stephanie; Erskine, Alicia; Crino, Rocco

    2004-04-01

    This is a naturalistic treatment outcome study investigating the impact of pre-existing antidepressant use on the effectiveness of group cognitive behaviour therapy (CBT) for social phobia. Of the 133 participants who completed the CBT program, 49 reported taking antidepressants (CBT + AD group), while 84 reported not taking antidepressants (CBT group). The treatment program involves 40 h of structured, group-based CBT over 7 weeks. The dependent measures included the Social Phobia Scale and Social Interaction Anxiety Scale, the Fear of Negative Evaluation Scale, the Depression, Anxiety and Stress Scale and the Short Form-12. Both the CBT + AD group and the CBT group improved significantly across treatment on all dependent measures. There were no significant differences between the groups on any outcome measure and the rate of improvement from pre- to post-treatment for both groups did not differ. Pre-existing antidepressants did not significantly enhance or detract from the positive treatment outcome of a structured, group-based CBT program for social phobia.

  4. The evolution of floral scent and olfactory preferences in pollinators: coevolution or pre-existing bias?

    PubMed

    Schiestl, Florian P; Dötterl, Stefan

    2012-07-01

    Coevolution is thought to be a major factor in shaping plant-pollinator interactions. Alternatively, plants may have evolved traits that fitted pre-existing preferences or morphologies in the pollinators. Here, we test these two scenarios in the plant family of Araceae and scarab beetles (Coleoptera, Scarabaeidae) as pollinators. We focused on floral volatile organic compounds (VOCs) and production/detection of VOCs by scarab beetles. We found phylogenetic structure in the production/detection of methoxylated aromatics in scarabs, but not plants. Within the plants, most of the compounds showed a well-supported pattern of correlated evolution with scarab-beetle pollination. In contrast, the scarabs showed no correlation between VOC production/detection and visitation to Araceae flowers, with the exception of the VOC skatole. Moreover, many VOCs were found in nonpollinating beetle groups (e.g., Melolonthinae) that are ancestors of pollinating scarabs. Importantly, none of the tested VOCs were found to have originated in pollinating taxa. Our analysis indicates a Jurassic origin of VOC production/detection in scarabs, but a Cretaceous/Paleocene origin of floral VOCs in plants. Therefore, we argue against coevolution, instead supporting the scenario of sequential evolution of floral VOCs in Araceae driven by pre-existing bias of pollinators. © 2012 The Author(s).

  5. Unmasking of undiagnosed pre-existing central diabetes insipidus after renal transplantation.

    PubMed

    Kim, David D W; Holdaway, Ian M

    2012-03-01

    Acquired central diabetes insipidus (CDI) often occurs abruptly after a cranial event causing hypothalamic or pituitary damage. We present a case of a patient with pre-existing and clinically unapparent CDI which was unmasked after renal transplantation. A 60 year old woman with end-stage renal failure due to autosomal dominant polycystic kidney disease (ADPKD) underwent renal transplantation. She was noted to be markedly polyuric and polydipsic after the transplant. A fluid deprivation test was unequivocally positive for CDI, and desmopressin treatment resulted in immediate symptom relief. Neuroimaging revealed a midline defect in the region of the hypothalamus. She had a history of an intracerebral aneurysm that had ruptured, requiring extensive neurosurgery many years previously. This case demonstrates a rare instance of pre-existing but clinically unapparent CDI unmasked by renal transplantation. It is likely that renal failure due to ADPKD disguised her CDI prior to transplantation. A previous intracerebral insult from an aneurysmal bleed is the likely cause of her vasopressin deficiency.

  6. Pre-existing sensory biases in the spectral domain in frogs: empirical results and methodological considerations.

    PubMed

    Gerhardt, H C; Humfeld, Sarah C

    2013-02-01

    In many species of anurans, advertisement calls excite only one of the two inner-ear organs. One prediction of the pre-existing bias hypothesis is that signal innovations that additionally excite the "untapped" organ will be more behaviorally effective than normal calls. However, recent studies have shown that females of three species with single-peaked calls that stimulate only the basilar papilla (BP) preferred single-peaked synthetic calls with a frequency typical of conspecific calls to two-peaked calls that also stimulated the amphibian papilla (AP). We report that in spring peepers (Pseudacris crucifer) that also produce single-peaked calls, females did not show a preference in choices between single-peaked and two-peaked synthetic calls. Thus, the addition of energy exciting the AP had a neutral effect on signal attractiveness. Together, these results are unsupportive of the pre-existing bias hypothesis. An alternative hypothesis is that positive fitness consequences of responding to sounds providing extraordinary spectral stimulation are required for a novel call to become established as a mate-attracting signal. Testing these ideas requires a taxonomically broader examination of responses to sounds with novel spectral complexity, and attention to some methodological details will improve the comparability of such studies.

  7. Receptor Signaling Directs Global Recruitment of Pre-existing Transcription Factors to Inducible Elements

    PubMed Central

    Cockerill, Peter N.

    2016-01-01

    Gene expression programs are largely regulated by the tissue-specific expression of lineage-defining transcription factors or by the inducible expression of transcription factors in response to specific stimuli. Here I will review our own work over the last 20 years to show how specific activation signals also lead to the wide-spread re-distribution of pre-existing constitutive transcription factors to sites undergoing chromatin reorganization. I will summarize studies showing that activation of kinase signaling pathways creates open chromatin regions that recruit pre-existing factors which were previously unable to bind to closed chromatin. As models I will draw upon genes activated or primed by receptor signaling in memory T cells, and genes activated by cytokine receptor mutations in acute myeloid leukemia. I also summarize a hit-and-run model of stable epigenetic reprograming in memory T cells, mediated by transient Activator Protein 1 (AP-1) binding, which enables the accelerated activation of inducible enhancers. PMID:28018147

  8. Kinetic Dissection of the Pre-existing Conformational Equilibrium in the Trypsin Fold*

    PubMed Central

    Vogt, Austin D.; Chakraborty, Pradipta; Di Cera, Enrico

    2015-01-01

    Structural biology has recently documented the conformational plasticity of the trypsin fold for both the protease and zymogen in terms of a pre-existing equilibrium between closed (E*) and open (E) forms of the active site region. How such plasticity is manifested in solution and affects ligand recognition by the protease and zymogen is poorly understood in quantitative terms. Here we dissect the E*-E equilibrium with stopped-flow kinetics in the presence of excess ligand or macromolecule. Using the clotting protease thrombin and its zymogen precursor prethrombin-2 as relevant models we resolve the relative distribution of the E* and E forms and the underlying kinetic rates for their interconversion. In the case of thrombin, the E* and E forms are distributed in a 1:4 ratio and interconvert on a time scale of 45 ms. In the case of prethrombin-2, the equilibrium is shifted strongly (10:1 ratio) in favor of the closed E* form and unfolds over a faster time scale of 4.5 ms. The distribution of E* and E forms observed for thrombin and prethrombin-2 indicates that zymogen activation is linked to a significant shift in the pre-existing equilibrium between closed and open conformations that facilitates ligand binding to the active site. These findings broaden our mechanistic understanding of how conformational transitions control ligand recognition by thrombin and its zymogen precursor prethrombin-2 and have direct relevance to other members of the trypsin fold. PMID:26216877

  9. Conducting qualitative research in the context of pre-existing peer and collegial relationships.

    PubMed

    McDermid, Fiona; Peters, Kath; Jackson, Debra; Daly, John

    2014-05-01

    To highlight issues and challenges faced in recruitment and interviewing during a study that sought to explore the transition of nurses into academic life and the associated ethical implications. This paper explores the challenges faced in conducting research where the potential participants are peers and workplace colleagues. There are advantages when conducting research with those among whom a pre-existing relationship is shared. However, difficulties can also arise. A methodological review was undertaken. Key database searches included CINAHL, MEDLINE, PubMed, Scopus and Google Scholar using the keywords as search terms. Studies were included if they described in detail issues surrounding qualitative interviewing of peers and colleagues. Management of the issues involved is discussed, with emphasis on boundaries, trust and rapport, the use of self-disclosure and maintaining confidentiality. Research involving peers and colleagues has received relatively little consideration in the literature. There are difficulties associated with interviewing participants with whom the researcher has a pre-existing and ongoing relationship in the same organisation. To ensure ethical conduct, strategies can be used to mitigate negative situations such as issues surrounding dual roles, practising reflexivity, trust and rapport, self-disclosure and confidentiality. It is imperative that dual roles are declared and acknowledged. Researchers need to be mindful of the difficulties that may occur and prioritise participants' confidentiality and privacy.

  10. Recruitment of pre-existing networks during the evolution of C4 photosynthesis.

    PubMed

    Reyna-Llorens, Ivan; Hibberd, Julian M

    2017-09-26

    During C4 photosynthesis, CO2 is concentrated around the enzyme RuBisCO. The net effect is to reduce photorespiration while increasing water and nitrogen use efficiencies. Species that use C4 photosynthesis have evolved independently from their C3 ancestors on more than 60 occasions. Along with mimicry and the camera-like eye, the C4 pathway therefore represents a remarkable example of the repeated evolution of a highly complex trait. In this review, we provide evidence that the polyphyletic evolution of C4 photosynthesis is built upon pre-existing metabolic and genetic networks. For example, cells around veins of C3 species show similarities to those of the C4 bundle sheath in terms of C4 acid decarboxylase activity and also the photosynthetic electron transport chain. Enzymes of C4 photosynthesis function together in gluconeogenesis during early seedling growth of C3Arabidopsis thaliana Furthermore, multiple C4 genes appear to be under control of both light and chloroplast signals in the ancestral C3 state. We, therefore, hypothesize that relatively minor rewiring of pre-existing genetic and metabolic networks has facilitated the recurrent evolution of this trait. Understanding how these changes are likely to have occurred could inform attempts to install C4 traits into C3 crops.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Author(s).

  11. Prevalence of staphylococcal enterotoxins in Staphylococcus pseudintermedius isolates from dogs with pyoderma and healthy dogs.

    PubMed

    Tanabe, Taishi; Toyoguchi, Midori; Hirano, Fumitaka; Chiba, Mei; Onuma, Kenta; Sato, Hisaaki

    2013-09-01

    To investigate the role of staphylococcal enterotoxins (SEs) produced by Staphylococcus pseudintermedius in the pathogenesis of pyoderma, isolates from dogs with pyoderma and healthy dogs were analyzed. According to reverse passive latex agglutination, 14/184 isolates (7.6%) from dogs with pyoderma and 9/87 (10.3%) from healthy dogs produced SEs (SEA, SEC or SED). According to multiplex PCR, 99 isolates (53.7%) from dogs with pyoderma and 97 (90.8%) from healthy dogs possessed one or more se genes. There was no significant difference regarding ses between dogs with pyoderma and healthy dogs. Therefore, SEs may not be a direct virulence factor in pyoderma.

  12. Blastomycosis-like pyoderma: response to systemic retinoid therapy.

    PubMed

    Kobraei, Kathy B; Wesson, Stanton K

    2010-11-01

    Blastomycosis-like pyoderma is a proliferative tissue response with multifactorial etiologies that may mimic other inflammatory and neoplastic skin disorders. It often occurs on sun damaged skin of immunocompromised patients. We report a case of blastomycosis-like pyoderma in a patient with underlying metastatic medullary carcinoma of the thyroid receiving treatment with sorafenib (a multikinase inhibitor). Prior treatments were unsuccessful. Our treatment with oral acitretin resulted in significant improvement. © 2010 The International Society of Dermatology.

  13. Pre-existing Pulmonary Diseases and Survival in Patients With Stage-dependent Lung Adenocarcinoma

    PubMed Central

    Jian, Zhi-Hong; Huang, Jing-Yang; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    Abstract Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival. Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan–Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma. A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10–2.58), 1.48 (95% CI, 1.14–1.93), and 1.27 (95% CI, 1.08–1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00–1.99) in women with stage I + II and 1.14 (95% CI, 1.04–1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12–1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12–1.63) for COPD + TB, 1.28 (95% CI, 1.01–1.63) for TB, and 1.15 (95%CI, 1.04–1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72–17.71) for asthma + COPD + TB. Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality. PMID:26962806

  14. Techniques of monitoring blood glucose during pregnancy for women with pre-existing diabetes.

    PubMed

    Moy, Foong Ming; Ray, Amita; Buckley, Brian S

    2014-04-30

    Self-monitoring of blood glucose is recommended as a key component of the management plan for diabetes therapy during pregnancy. No existing systematic reviews consider the benefits/effectiveness of various techniques of blood glucose monitoring on maternal and infant outcomes among pregnant women with pre-existing diabetes. The effectiveness of the various monitoring techniques is unclear. To compare techniques of blood glucose monitoring and their impact on maternal and infant outcomes among pregnant women with pre-existing diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 August 2013), searched reference lists of retrieved studies and contacted trial authors. Randomised controlled trials (RCTs) comparing techniques of blood glucose monitoring including self blood glucose monitoring, continuous glucose monitoring (CGM) or clinic monitoring among pregnant women with pre-existing diabetes mellitus (Type 1 or Type 2). Trials investigating timing and frequency of monitoring were also included. Quasi-RCTs and RCTs using a cluster-randomised design were eligible for inclusion but none were identified. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. The search of the Pregnancy and Childbirth Group's Trials Register identified 21 trial reports. Following application of eligibility criteria, nine trials were included in this review. The included trials involved a total of 506 women (436 women with Type 1 diabetes and 70 women with Type 2 diabetes). All trials originated from European countries and the USA. None of the studies included women with gestational diabetes. Five of the nine included studies were at moderate risk of bias and four studies were at low to moderate risk of bias. Primary outcomes were maternal glycaemic control (fasting blood glucose and HbA1c) and infant birthweight or macrosomia.Various methods of

  15. Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy.

    PubMed

    Louis Jeune, Vedell; Joergensen, Jakob A; Hajjar, Roger J; Weber, Thomas

    2013-04-01

    Adeno-associated virus (AAV)-based vectors are promising tools for gene therapeutic applications, in part because AAVs are nonpathogenic viruses, and vectors derived from them can drive long-term transgene expression without integration of the vector DNA into the host genome. AAVs are not strongly immunogenic, but they can, nonetheless, give rise to both a cellular and humoral immune response. As a result, a significant fraction of potential patients for AAV-based gene therapy harbors pre-existing antibodies against AAV. Because even very low levels of antibodies can prevent successful transduction, antecedent anti-AAV antibodies pose a serious obstacle to the universal application of AAV gene therapy. In this review, we discuss the current knowledge of the role of anti-AAV antibodies in AAV-based gene therapy with a particular emphasis on approaches to overcome the hurdle that they pose.

  16. Hypermagnesemia induced by massive cathartic ingestion in an elderly woman without pre-existing renal dysfunction.

    PubMed

    Kontani, Makoto; Hara, Akinori; Ohta, Shinji; Ikeda, Takayuki

    2005-05-01

    A 76-year-old woman was referred to our hospital for unresponsiveness and hypotension. She had developed constipation that had led to ileus and had received 34 g of magnesium citrate (Magcolol P) orally the day before. She was lethargic, her blood pressure was less than 50 mmHg, and electrocardiogram (ECG) revealed sinus arrest with junctional escape rhythm. Her serum concentration of magnesium (Mg) was markedly elevated (16.6 mg/dl =13.7 mEq/l). Emergency colonoscopy revealed ischemic colitis. As her condition ameliorated, her renal function returned to normal. Hence, the present case suggests that severe hypermagnesemia can occur in the absence of pre-existing renal dysfunction in elderly patients with gastrointestinal diseases.

  17. Sodium valproate induced gingival enlargement with pre-existing chronic periodontitis

    PubMed Central

    Joshipura, Vaibhavi

    2012-01-01

    Gingival enlargement is a common clinical feature of gingival and periodontal diseases. Currently, more than 20 prescription medications are associated with gingival enlargement. Although the mechanisms of action may be different, the clinical and microscopic appearance of drug-induced gingival enlargement is similar with any drug. Gingival enlargement produces esthetic changes, and clinical symptoms including pain, tenderness, bleeding, speech disturbances, abnormal tooth movement, dental occlusion problems, enhancement of caries development and periodontal disorders. Sodium valproate is considered to produce gingival enlargement, but very rarely. This case report features sodium valproate induced gingival enlargement in a patient with pre-existing chronic periodontitis, who came to the Dental Department, Chinmaya Mission Hospital, Bangalore. The case is special as the patient did not develop the enlargement in spite of taking phenytoin for 1 year and developed enlargement with sodium valproate within 6 months. PMID:23055600

  18. Pre-existing arterial pathologic changes affecting arteriovenous fistula patency and cardiovascular mortality in hemodialysis patients.

    PubMed

    Lee, Ja Young; Kim, Young Ok

    2017-09-01

    The radiocephalic arteriovenous fistula (AVF) provides optimal vascular access for hemodialysis; it has a higher long-term patency rate and fewer complications than other vascular access methods. However, the AVF has a high primary failure rate. The presence of small-diameter vessels at anastomosis sites is an important risk factor for AVF failure. However, in a recent study, despite selecting an adequate artery and vein for creating an AVF by routine preoperative vascular mapping, AVF maturation and primary failure occurred. Thus, pre-existing arteriosclerosis at AVF anastomosis sites likely contributes to AVF failure. In this review, we discuss the relationship between pathologic changes and AVF patency in hemodialysis patients. Because arteriosclerosis of the major arteries such as the coronary and carotid arteries is associated with cardiovascular mortality, we also review the impact of arteriosclerosis of upper arm arteries at AVF anastomosis sites on cardiovascular mortality in hemodialysis patients.

  19. Effect of pre-existing immobile dislocations on the evolution of geometrically necessary dislocations during fatigue

    NASA Astrophysics Data System (ADS)

    Irastorza-Landa, Ainara; Grilli, Nicolò; Van Swygenhoven, Helena

    2017-07-01

    The role of pre-existing mobile and immobile dislocation densities on the evolution of geometrical necessary dislocation densities (GNDs) during cyclic fatigue in shear is studied using a continuum dislocation-based model incorporated in a crystal plasticity finite element scheme. Clusters with different immobile dislocation densities are implemented in a homogeneous medium containing a certain mobile dislocation density. It is found that whether GND walls are formed around the initial immobile cluster (or not) strongly depends on the absolute values of initial mobile dislocation density and on the ratio between mobile and immobile densities. The results are discussed in terms of the apparent GND densities experimentally obtained using Laue micro-diffraction.

  20. From Pre-Existing Renal Failure to Perioperative Renal Protection: The Anesthesiologist’s Dilemmas

    PubMed Central

    Domi, Rudin; Huti, Gentian; Sula, Hektor; Baftiu, Nehat; Kaci, Myzafer; Bodeci, Artan; Pesha, Albert

    2016-01-01

    Context Pre-existing renal dysfunction presents specific features that anesthesiologists must deal with. Anesthesia and renal function are connected and can interfere with each other. Induced hypotension anesthesia and the toxic effects of anesthetic drugs can further deteriorate renal function. Evidence Acquisition Decreased renal function can prolong anesthetic drug effects by decreased elimination of these drugs. Anesthesia can deteriorate renal function and decreased renal function can interfere with drug elimination leading to their prolonged effect. The anesthesiologist must understand all the physiological aspects of the patient, renal protection, and the relationships between anesthetic drugs and renal function. This review article aims to summarize these aspects. Results Perioperative renal failure and renal protection is a crucial moment in clinical practice of every anesthesiologist. Conclusions Good knowledges for renal function remain a hallmark of daily practice of the anesthesiologist, considering renal function as an important determinant factor in anesthesia practice. PMID:27642570

  1. Numerical Study on Coalescence of Pre-Existing Flaw Pairs in Rock-Like Material

    NASA Astrophysics Data System (ADS)

    Li, Huan-Qiang; Wong, Louis Ngai Yuen

    2014-11-01

    The present numerical study, which is an extension of our previous numerical analysis on cracking processes of a single pre-existing flaw, focuses on the coalescence of two pre-existing parallel open flaws in rock subjected to a uniaxial compressive loading. To facilitate a systematic investigation, the arrangements of the flaw pair are classified into 11 categories. Simulations engaging AUTODYN are conducted on each category. The numerical results are compared with some published physical experimental test results. Eleven typical coalescence patterns are obtained, which are in good agreement with the experimental results, which include two coalescence patterns obtained in flaw pair arrangements (II) and (VIII″) not being reported in previous studies. The information gathered in the simulations helps identify the type (tensile/shear) of each crack segment involved in the coalescence. Most of the coalescence cracks initiate at or around the flaw tips, except those in flaw pair arrangements (II) and (IX') with a very short ligament length, in which the coalescence cracks initiate on the flaw surfaces away from the flaw tip regions. Based on the numerical simulation results, the properties of the 11 coalescence patterns are obtained. Except those in flaw pair arrangements (II) and (IX'), the other coalescence patterns can be interpreted with respect to the basic crack types—tensile wing crack, horsetail crack and anti-wing crack. In addition, based on the type of crack segments involved in coalescence, namely tensile and shear, the coalescence can be classified into T mode (tensile mode), S mode (shear mode) and TS mode (mixed tensile-shear mode).

  2. Malignant Precursor Cells Pre-Exist in Human Breast DCIS and Require Autophagy for Survival

    PubMed Central

    Espina, Virginia; Mariani, Brian D.; Gallagher, Rosa I.; Tran, Khoa; Banks, Stacey; Wiedemann, Joy; Huryk, Heather; Mueller, Claudius; Adamo, Luana; Deng, Jianghong; Petricoin, Emanuel F.; Pastore, Lucia; Zaman, Syed; Menezes, Geetha; Mize, James; Johal, Jasbir; Edmiston, Kirsten; Liotta, Lance A.

    2010-01-01

    Background While it is accepted that a majority of invasive breast cancer progresses from a ductal carcinoma in situ (DCIS) precursor stage, very little is known about the factors that promote survival of DCIS neoplastic cells within the hypoxic, nutrient deprived intraductal microenvironment. Methodology and Principal Findings We examined the hypothesis that fresh human DCIS lesions contain pre-existing carcinoma precursor cells. We characterized these cells by full genome molecular cytogenetics (Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray, 59 endpoints), and demonstrated that autophagy is required for survival and anchorage independent growth of the cytogenetically abnormal tumorigenic DCIS cells. Ex vivo organoid culture of fresh human DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct-like 3-D structures in culture within 2–4 weeks; b) tumorigenicity in NOD/SCID mice; c) cytogenetically abnormal (copy number loss or gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue; d) in vitro migration and invasion of autologous breast stroma; and e) up-regulation of signal pathways linked to, and components of, cellular autophagy. Multiple autophagy markers were present in the patient's original DCIS lesion and the mouse xenograft. We tested whether autophagy was necessary for survival of cytogenetically abnormal DCIS cells. The lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed ex vivo invasion of autologous stroma, induced apoptosis, suppressed autophagy associated proteins including Atg5, AKT/PI3 Kinase and mTOR, eliminated cytogenetically abnormal spheroid forming cells from

  3. Severity of pre-existing psychiatric illness and response to the Great East Japan Earthquake.

    PubMed

    Funayama, Michitaka; Mizushima, Jin

    2013-10-01

    Reports have described how psychiatric patients respond to disasters. However, previous reports on the response depending on diagnostic categories have provided no clear consensus. Here we analyzed response to the Great East Japan Earthquake of March 11, 2011, among psychiatric patients in light of severity of pre-existing psychiatric illness. We studied psychiatric change among a population of psychiatric outpatients in Tochigi prefecture, located ~160 km (~100 miles) southeast of the Fukushima nuclear power plant, in an area that suffered moderate damage from the earthquake and radiation. A total of 294 psychiatric outpatients was assessed using the Global Assessment of Functioning (GAF-F). A change of ≥10 points in the GAF-F score was counted as a change in symptoms. The data were stratified by disease category, gender, and GAF-F score and analyzed using the Fisher's exact test. In the 2 months after the earthquake, 5.4% of patients showed evidence of a change in symptoms, with 4.1% worsening and 1.4% improving. Compared with patients having a GAF-F score ≤50, significantly more patients with a score >50 showed evidence of worsening symptoms. No significant difference was found with respect to gender or diagnostic category for patients with worsened or improved symptoms. Our findings reveal that a relatively small percent of patients with pre-existing psychiatric diseases showed evidence of a change in symptoms and that patients with mild-to-moderate psychiatric illness are potentially vulnerable to the impacts of a natural disaster. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector.

    PubMed

    Knuchel, Marlyse C; Marty, René R; Morin, Teldja Neige Azzouz; Ilter, Orhan; Zuniga, Armando; Naim, Hussein Y

    2013-03-01

    Measles virus (MV) vectors are promising candidates for designing new recombinant vaccines since the parental live vaccines have a well-known safety and efficacy record. Like all viral vectors, the MV vector efficacy in inducing a protecting immune answer could be affected by the pre-existing immunity among the human population. In order to determine the optimal immunization route and regimen, we mimicked a MV pre-immunity by passively administrating MV neutralizing antibodies (MV-nAb) prior intramuscular (i.m.) and/or intranasal (i.n.) immunization with recombinant MV expressing the SIV-gag antigen (rMV-SIVgag). Our results revealed that 500 mIU of MV-nAb allowed the induction of a humoral and cellular immune response against the vector and the transgene, while higher titers of the MV-nAb were significantly inhibitory. In a prime-boost regimen, in the presence of MV-nAb, the intranasal-intramuscular (i.n.-i.m.) or intramuscular-intramuscular (i.m.-i.m.) routes induced higher humoral immune responses against the vector and the transgene (SIV-gag). In naive animals, cellular immune response was significantly higher by i.m. immunization; however, MV pre-immunity did not seem to affect the cellular immune response after an i.n. immunization.   In summary, we show that a pre-existing immunity of up to 500 mIU anti-MV neutralizing antibodies had little effect on the replication of rMV and did not inhibit the induction of significant humoral and cellular immune responses in immune-competent mice.

  5. A framework for the merging of pre-existing and correspondenceless 3D statistical shape models.

    PubMed

    Pereañez, Marco; Lekadir, Karim; Butakoff, Constantine; Hoogendoorn, Corné; Frangi, Alejandro F

    2014-10-01

    The construction of statistical shape models (SSMs) that are rich, i.e., that represent well the natural and complex variability of anatomical structures, is an important research topic in medical imaging. To this end, existing works have addressed the limited availability of training data by decomposing the shape variability hierarchically or by combining statistical and synthetic models built using artificially created modes of variation. In this paper, we present instead a method that merges multiple statistical models of 3D shapes into a single integrated model, thus effectively encoding extra variability that is anatomically meaningful, without the need for the original or new real datasets. The proposed framework has great flexibility due to its ability to merge multiple statistical models with unknown point correspondences. The approach is beneficial in order to re-use and complement pre-existing SSMs when the original raw data cannot be exchanged due to ethical, legal, or practical reasons. To this end, this paper describes two main stages, i.e., (1) statistical model normalization and (2) statistical model integration. The normalization algorithm uses surface-based registration to bring the input models into a common shape parameterization with point correspondence established across eigenspaces. This allows the model fusion algorithm to be applied in a coherent manner across models, with the aim to obtain a single unified statistical model of shape with improved generalization ability. The framework is validated with statistical models of the left and right cardiac ventricles, the L1 vertebra, and the caudate nucleus, constructed at distinct research centers based on different imaging modalities (CT and MRI) and point correspondences. The results demonstrate that the model integration is statistically and anatomically meaningful, with potential value for merging pre-existing multi-modality statistical models of 3D shapes. Copyright © 2014 Elsevier B

  6. Effects of Pre-Existing Target Structure on the Formation of Large Craters

    NASA Technical Reports Server (NTRS)

    Barnouin-Jha, O. S.; Cintala, M. J.; Crawford, D. A.

    2003-01-01

    The shapes of large-scale craters and the mechanics responsible for melt generation are influenced by broad and small-scale structures present in a target prior to impact. For example, well-developed systems of fractures often create craters that appear square in outline, good examples being Meteor Crater, AZ and the square craters of 433 Eros. Pre-broken target material also affects melt generation. Kieffer has shown how the shock wave generated in Coconino sandstone at Meteor crater created reverberations which, in combination with the natural target heterogeneity present, created peaks and troughs in pressure and compressed density as individual grains collided to produce a range of shock mineralogies and melts within neighboring samples. In this study, we further explore how pre-existing target structure influences various aspects of the cratering process. We combine experimental and numerical techniques to explore the connection between the scales of the impact generated shock wave and the pre-existing target structure. We focus on the propagation of shock waves in coarse, granular media, emphasizing its consequences on excavation, crater growth, ejecta production, cratering efficiency, melt generation, and crater shape. As a baseline, we present a first series of results for idealized targets where the particles are all identical in size and possess the same shock impedance. We will also present a few results, whereby we increase the complexities of the target properties by varying the grain size, strength, impedance and frictional properties. In addition, we investigate the origin and implications of reverberations that are created by the presence of physical and chemical heterogeneity in a target.

  7. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COAL MINING POINT... establishing effluent limitations for pre-existing discharges at coal remining operations, in accordance with the requirements set forth in subpart G; Coal Remining. The requirements specify that...

  8. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COAL MINING POINT... establishing effluent limitations for pre-existing discharges at coal remining operations, in accordance with the requirements set forth in Subpart G; Coal Remining. The requirements specify that...

  9. I know I've seen you before: Distinguishing recent-single-exposure-based familiarity from pre-existing familiarity.

    PubMed

    Gimbel, Sarah I; Brewer, James B; Maril, Anat

    2017-03-01

    This study examines how individuals differentiate recent-single-exposure-based familiarity from pre-existing familiarity. If these are two distinct cognitive processes, are they supported by the same neural bases? This study examines how recent-single-exposure-based familiarity and multiple-previous-exposure-based familiarity are supported and represented in the brain using functional MRI. In a novel approach, we first behaviorally show that subjects can divide retrieval of items in pre-existing memory into judgments of recollection and familiarity. Then, using functional magnetic resonance imaging, we examine the differences in blood oxygen level dependent activity and regional connectivity during judgments of recent-single-exposure-based and pre-existing familiarity. Judgments of these two types of familiarity showed distinct regions of activation in a whole-brain analysis, in medial temporal lobe (MTL) substructures, and in MTL substructure functional-correlations with other brain regions. Specifically, within the MTL, perirhinal cortex showed increased activation during recent-single-exposure-based familiarity while parahippocampal cortex showed increased activation during judgments of pre-existing familiarity. We find that recent-single-exposure-based and pre-existing familiarity are represented as distinct neural processes in the brain; this is supported by differing patterns of brain activation and regional correlations. This spatially distinct regional brain involvement suggests that the two separate experiences of familiarity, recent-exposure-based familiarity and pre-existing familiarity, may be cognitively distinct.

  10. EVIDENCE FOR PRE-EXISTING DUST IN THE BRIGHT TYPE IIn SN 2010jl

    SciTech Connect

    Andrews, J. E.; Clayton, Geoffrey C.; Clem, J.; Landolt, A. E-mail: landolt@phys.lsu.edu E-mail: jclem@phys.lsu.edu

    2011-08-15

    SN 2010jl was an extremely bright, Type IIn supernova (SN) which showed a significant infrared (IR) excess no later than 90 days after explosion. We have obtained Spitzer 3.6 and 4.5 {mu}m and JHK observations of SN 2010jl {approx}90 days post-explosion. Little to no reddening in the host galaxy indicated that the circumstellar material lost from the progenitor must lie in a torus inclined out of the plane of the sky. The likely cause of the high mid-IR flux is the reprocessing of the initial flash of the SN by pre-existing circumstellar dust. Using a three-dimensional Monte Carlo radiative-transfer code, we have estimated that between 0.03 and 0.35 M{sub sun} of dust exists in a circumstellar torus around the SN located 6 x 10{sup 17} cm away from the SN and inclined between 60 deg. and 80 deg. to the plane of the sky. On day 90, we are only seeing the illumination of approximately 5% of this torus, and expect to see an elevated IR flux from this material up until day {approx} 450. It is likely this dust was created in a luminous blue variable (LBV) like mass-loss event of more than 3 M{sub sun}, which is large but consistent with other LBV progenitors such as {eta} Carinae.

  11. Pre-existent expectancy effects in the relationship between caffeine and performance.

    PubMed

    Elliman, Nicola A; Ash, Jennifer; Green, Michael W

    2010-10-01

    The present study investigated the impact of pre-existent expectancy regarding the effects of the caffeine load of a drink and the perception of the caffeine content on subjective mood and vigilance performance. Caffeine deprived participants (N=25) were tested in four conditions (within subjects design), using a 2×2 design, with caffeine load and information regarding the caffeine content of the drink. In two sessions, they were given caffeinated coffee and in two were given decaffeinated coffee. Within these two conditions, on one occasion they were given accurate information about the drink and on the other they were given inaccurate information about the drink. Mood and vigilance performance were assessed post ingestion. Caffeine was found to enhance performance, but only when participants were accurately told they were receiving it. When decaffeinated coffee was given, performance was poorer, irrespective of expectancy. However, when caffeine was given, but participants were told it was decaffeinated coffee, performance was as poor as when no caffeine had been administered. There were no easily interpretable effects on mood. The pharmacological effects of caffeine appear to act synergistically with expectancy.

  12. Experimental study on crack coalescence mechanisms of pre-existing flaws under blast loading

    NASA Astrophysics Data System (ADS)

    Yue, Zhong-wen; Yang, Ren-shu; Ma, Xin-min; Guo, Dong-ming

    2008-11-01

    The PMMA model transmission-type experiment of dynamic caustics was carried out to simulate the fracture blasting process of material containing pre-existing flaws using the dynamic caustic-test system. The mechanism of the fracture coalescence among four prefabricated flaws with echelon geometry distribution was studied under blast loading. The experiment results show that two wing cracks respectively coalescing with the flaw F2 and flaw F3 appear at both tips of the flaw F1 closest to the blasthole. Whereas the flaw F4 doesn't produce wing cracks, the flaw F2 and flaw F3 also respectively generate two wing cracks which don't link up the flaw F4. Crack propagation is greatly affected by preexisting flaws. During the whole fracture process, the wing crack velocity oscillates with the increase of crack propagating time. The value of dynamic stress intensity factor reaches the maximum in a moment and then gradually decreases. The changes of dynamic stress intensity factor also oscillate in the whole time. Furthermore, the value of dynamic stress intensity factor KdII is smaller than that of dynamic stress intensity factor KdI. The results of the present research can provide the theoretical basis for the study on blasting of rock containing flaws.

  13. Psychological distress in an earthquake-devastated area with pre-existing high rate of suicide.

    PubMed

    Tachibana, Akira; Kitamura, Hideaki; Shindo, Masanobu; Honma, Hiroko; Someya, Toshiyuki

    2014-10-30

    On 12 March 2011 an earthquake devastated the Matsunoyama and Matsudai districts of Tōkamachi City, Niigata, Japan. These areas had high pre-existing suicide rates, especially among the elderly. We investigated whether mental health status became worse among the sufferers 5 months after the earthquake, and what kind of factors were implicated in any changes. A 15-item questionnaire that tapped earthquake-related variables and the Kessler 10 Psychological Distress Scale to measure psychological distress were distributed to 1923 residents aged over 40 years. The mean age (S.D.) of the total 1731 respondents (male, 805; female, 926) was 68.2 (13.1) years. Of these, we assessed K10 scores from 1346 respondents. The mean scores (S.D.) for K10 and K6 (six selected items from the K10) were 5.8 (6.3) and 3.4 (3.9), respectively. Among the respondents, 9.1% and 3.2% obtained a score of K10 ≥15 and K6 ≥13, respectively. These scores showed slightly higher psychological distress, especially among the elderly, in comparison with existing community-based data. Categorical regression analysis revealed significant and relatively strong effects of initial psychological impact, decrease in sleep hours, advanced age, and decrease in interpersonal relationships within the community on the K10 score. The last item suggests the importance of socio-environmental factors in post-disaster mental health.

  14. Plasticity induced by pre-existing defects during high strain-rate loading

    NASA Astrophysics Data System (ADS)

    Bringa, Eduardo

    2014-03-01

    High strain-rate deformation of metals has been typically studied for perfect monocrystals. Computational advances now allow more realistic simulations of materials including defects, which lower the Hugoniot Elastic Limit, and lead to microstructures differing from the ones from perfect monocrystals. As pre-existing defects one can consider vacancy clusters, dislocation loops, grain boundaries, etc. New analysis tools allow analysis of dislocation densities and twin fractions, for both f.c.c. and b.c.c. metals. Recent results for defective single crystal Ta [Tramontina et al.., High Energy Den. Phys. 10, 9 (2014), and Ruestes et al., Scripta Mat. 68, 818 (2013)], and for polycrystalline b.c.c metals [Tang et al., Mat. Sci. Eng. A 580, 414 (2013), and Gunkelmann et al., Phys. Rev. B 86, 144111 (2012)] will be highlighted, alongside new results for nanocrystalline Cu, Ta, Fe, and Zr [Ruestes et al., Scripta Mat. 71, 9 (2014)]. This work has been carried out in collaboration with D. Tramontina, C. Ruestes, E. Millan, J. Rodriguez-Nieva, M.A. Meyers, Y. Tang, H. Urbassek, N. Gunkelmann, A. Stukowski, M. Ruda, G. Bertolino, D. Farkas, A. Caro, J. Hawreliak, B. Remington, R. Rudd, P. Erhart, R. Ravelo, T. Germann, N. Park, M. Suggit, S. Michalik, A. Higginbotham and J. Wark. Funding by PICT2008-1325 and SeCTyP U.N. Cuyo.

  15. Successful resuscitation of serious bupivacaine intoxication in a patient with pre-existing heart failure.

    PubMed

    Favier, Jean-Christophe; Da Conceiçao, Manuel; Fassassi, Mikaïla; Allanic, Laurent; Steiner, Thierry; Pitti, Raphaël

    2003-01-01

    In dogs intoxicated with bupivacaine, clonidine is effective to treat conduction disturbances and dobutamine corrects myocardial depression. We report the case of a patient who experienced severe bupivacaine cardiotoxicity and who was treated successfully using these medications. In a patient with pre-existing heart failure a surgical procedure to fix a humeral fracture was necessary. Preoperatively, heart failure was controlled with transcutaneous nitroglycerin and iv deslanoside. A bupivacaine bolus was administered iv accidentally (a mixture of bupivacaine 75 mg, 15 micro g clonidine). The patient developed nodal rhythm with extreme bradycardia, severe shock and convulsions. Seizures were controlled with thiopentone/succinylcholine. Epinephrine iv boluses (0.1 mg x 3) restored blood pressure (BP) to 50/30 mmHg and heart rate (HR) to 60 (nodal rhythm). Following 75 micro g clonidine iv, BP rose to 90/70 and HR to 90 min. Cardiac rhythm reverted to sinus rhythm with first degree atrio-ventricular block. Echocardiography showed hyperkinesia and relative hypovolemia that was controlled with iv administration of terlipressin and glucagon. Subsequent dobutamine infusion stabilized hemodynamic conditions. It was decided to proceed with surgery using a midazolam/sufentanil based general anesthetic. In the intensive care unit, recovery, extubation and weaning from the dobutamine infusion were realized within 16 hr of the event. In this patient with preoperative heart failure, clonidine was effective to treat bupivacaine induced conduction disturbances. Epinephrine and dobutamine were effective to treat myocardial depression and terlipressin effectively controlled vasodilatation.

  16. Exacerbation of pre-existing epilepsy by mild head injury: a five patient series.

    PubMed

    Tai, P C; Gross, D W

    2004-08-01

    While the risk of developing seizures following a mild head injury has been reported and is thought to be low, the effect of mild head injury on patients with a pre-existing seizure disorder has not been reported. We present a series of cases where a strong temporal relationship between mild head injury and worsening of seizure frequency was observed. Five cases were identified and reviewed in detail. Information was derived from clinic and hospital charts with attention to the degree of injury, pre- and postinjury seizure patterns and frequency. One patient has primary generalized epilepsy and four have localization related epilepsy. Prior to the head injury, three of the patients were seizure free (range: two to 24 years). The patients suffered from mild head injuries with no or transient loss of consciousness and no focal neurological deficits. In all cases, the patients experienced a worsening of seizure control within days of the injury. In one case, the patient's seizure pattern returned to baseline one year after the accident, while in the remaining four cases, the patients continue to have medically refractory seizures. A close temporal relationship between mild head injury and a worsening of seizure control was observed in five patients with epilepsy. Although further study is required, this observation suggests that a head injury that would be considered benign in the general population can have serious consequences such as recurrence of seizures and medical intractability in patients with epilepsy.

  17. No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

    PubMed

    Heller, Monika K; Chapman, Sarah C E; Horne, Rob

    2017-04-01

    Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (rCorrect Recall = -.273), were less able to differentiate between listed and unlisted side effects (rRecognition Sensitivity = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (rside effect attribution = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

  18. Solid particle impingement erosion characteristics of cylindrical surfaces, pre-existing holes and slits

    NASA Technical Reports Server (NTRS)

    Rao, P. V.; Buckley, D. H.

    1983-01-01

    The erosion characteristics of aluminum cylinders sand-blasted with both spherical and angular erodent particles were studied and compared with results from previously studied flat surfaces. The cylindrical results are discussed with respect to impact conditions. The relationship between erosion rate and pit morphology (width, depth, and width to depth ratio) is established. The aspects of (1) erosion rate versus time curves on cylindrical surfaces; (2) long-term exposures; and (3) erosion rate versus time curves with spherical and angular particles are presented. The erosion morphology and characteristics of aluminum surfaces with pre-existing circular cylindrical and conical holes of different sizes were examined using weight loss measurements, scanning electron microscopy, a profilometer, and a depth gage. The morphological features (radial and concentric rings) are discussed with reference to flat surfaces, and the erosion features with spherical microglass beads. The similarities and differences of erosion and morphological features are highlighted. The erosion versus time curves of various shapes of holes are discussed and are compared with those of a flat surface. The erosion process at slits is considered.

  19. Endoscopic skull base training using 3D printed models with pre-existing pathology.

    PubMed

    Narayanan, Vairavan; Narayanan, Prepageran; Rajagopalan, Raman; Karuppiah, Ravindran; Rahman, Zainal Ariff Abdul; Wormald, Peter-John; Van Hasselt, Charles Andrew; Waran, Vicknes

    2015-03-01

    Endoscopic base of skull surgery has been growing in acceptance in the recent past due to improvements in visualisation and micro instrumentation as well as the surgical maturing of early endoscopic skull base practitioners. Unfortunately, these demanding procedures have a steep learning curve. A physical simulation that is able to reproduce the complex anatomy of the anterior skull base provides very useful means of learning the necessary skills in a safe and effective environment. This paper aims to assess the ease of learning endoscopic skull base exposure and drilling techniques using an anatomically accurate physical model with a pre-existing pathology (i.e., basilar invagination) created from actual patient data. Five models of a patient with platy-basia and basilar invagination were created from the original MRI and CT imaging data of a patient. The models were used as part of a training workshop for ENT surgeons with varying degrees of experience in endoscopic base of skull surgery, from trainees to experienced consultants. The surgeons were given a list of key steps to achieve in exposing and drilling the skull base using the simulation model. They were then asked to list the level of difficulty of learning these steps using the model. The participants found the models suitable for learning registration, navigation and skull base drilling techniques. All participants also found the deep structures to be accurately represented spatially as confirmed by the navigation system. These models allow structured simulation to be conducted in a workshop environment where surgeons and trainees can practice to perform complex procedures in a controlled fashion under the supervision of experts.

  20. Different insulin types and regimens for pregnant women with pre-existing diabetes.

    PubMed

    O'Neill, Sinéad M; Kenny, Louise C; Khashan, Ali S; West, Helen M; Smyth, Rebecca Md; Kearney, Patricia M

    2017-02-03

    Insulin requirements may change during pregnancy, and the optimal treatment for pre-existing diabetes is unclear. There are several insulin regimens (e.g. via syringe, pen) and types of insulin (e.g. fast-acting insulin, human insulin). To assess the effects of different insulin types and different insulin regimens in pregnant women with pre-existing type 1 or type 2 diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 October 2016), ClinicalTrials.gov (17 October 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 17 October 2016), and the reference lists of retrieved studies. We included randomised controlled trials (RCTs) that compared different insulin types and regimens in pregnant women with pre-existing diabetes.We had planned to include cluster-RCTs, but none were identified. We excluded quasi-randomised controlled trials and cross-over trials. We included studies published in abstract form and contacted the authors for further details when applicable. Conference abstracts were superseded by full publications. Two review authors independently assessed trials for inclusion, conducted data extraction, assessed risk of bias, and checked for accuracy. We assessed the quality of the evidence using the GRADE approach. The findings in this review were based on very low-quality evidence, from single, small sample sized trial estimates, with wide confidence intervals (CI), some of which crossed the line of no effect; many of the prespecified outcomes were not reported. Therefore, they should be interpreted with caution. We included five trials that included 554 women and babies (four open-label, multi-centre, two-arm trials; one single centre, four-arm RCT). All five trials were at a high or unclear risk of bias due to lack of blinding, unclear methods of randomisation, and selective reporting of outcomes. Pooling of data from the trials was not possible, as each trial looked at a different comparison.1. One

  1. Diagnosis and treatment delays among elderly breast cancer patients with pre-existing mental illness.

    PubMed

    Iglay, Kristy; Santorelli, Melissa L; Hirshfield, Kim M; Williams, Jill M; Rhoads, George G; Lin, Yong; Demissie, Kitaw

    2017-07-19

    This study aimed to compare diagnosis and treatment delays in elderly breast cancer patients with and without pre-existing mental illness. A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results-Medicare data including 16,636 women 68+ years, who were diagnosed with stage I-IIIa breast cancer in the United States from 2005 to 2007. Mental illness was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes recorded on inpatient and outpatient claims during the 3 years prior to breast cancer diagnosis. Patients were classified as having no mental illness, anxiety, depression, anxiety and depression, or severe mental illness (bipolar disorder, schizophrenia, and other psychotic disorder). Multivariable binomial regression was used to assess the association between mental illness and delays of ≥60 and ≥90 days after adjustment for confounders. Patients with comorbid anxiety and depression had an increased risk for diagnosis delay of ≥90 days from symptom recognition (RR 1.11; 95% CI 1.00, 1.23), and those with severe mental illness had an increased risk for initial treatment delay of ≥60 days from diagnosis (RR 1.36; 95% CI 1.06, 1.74). Patients with any mental illness experienced an increased risk for adjuvant chemotherapy delay of ≥90 days from last operation (RR 1.13; 95% CI 1.01, 1.26) and each category of mental illness, except depression, showed a non-significant trend for this association. Breast cancer patients with mental illness should be closely managed by a cross-functional care team, including a psychiatrist, a primary care physician, and an oncologist, to ensure adequate care is received within an appropriate timeframe.

  2. Techniques of monitoring blood glucose during pregnancy for women with pre-existing diabetes.

    PubMed

    Moy, Foong Ming; Ray, Amita; Buckley, Brian S; West, Helen M

    2017-06-11

    Self-monitoring of blood glucose (SMBG) is recommended as a key component of the management plan for diabetes therapy during pregnancy. No existing systematic reviews consider the benefits/effectiveness of various techniques of blood glucose monitoring on maternal and infant outcomes among pregnant women with pre-existing diabetes. The effectiveness of the various monitoring techniques is unclear. To compare techniques of blood glucose monitoring and their impact on maternal and infant outcomes among pregnant women with pre-existing diabetes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016), searched reference lists of retrieved studies and contacted trial authors. Randomised controlled trials (RCTs) and quasi-RCTs comparing techniques of blood glucose monitoring including SMBG, continuous glucose monitoring (CGM) or clinic monitoring among pregnant women with pre-existing diabetes mellitus (type 1 or type 2). Trials investigating timing and frequency of monitoring were also included. RCTs using a cluster-randomised design were eligible for inclusion but none were identified. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. This review update includes at total of 10 trials (538) women (468 women with type 1 diabetes and 70 women with type 2 diabetes). The trials took place in Europe and the USA. Five of the 10 included studies were at moderate risk of bias, four studies were at low to moderate risk of bias, and one study was at high risk of bias. The trials are too small to show differences in important outcomes such as macrosomia, preterm birth, miscarriage or death of baby. Almost all the reported GRADE outcomes were assessed as being very low-quality evidence. This was due to design limitations in the studies, wide confidence intervals, small

  3. Modulation of a pre-existing conformational equilibrium tunes adenylate kinase activity.

    PubMed

    Ådén, Jörgen; Verma, Abhinav; Schug, Alexander; Wolf-Watz, Magnus

    2012-10-10

    Structural plasticity is often required for distinct microscopic steps during enzymatic reaction cycles. Adenylate kinase from Escherichia coli (AK(eco)) populates two major conformations in solution; the open (inactive) and closed (active) state, and the overall turnover rate is inversely proportional to the lifetime of the active conformation. Therefore, structural plasticity is intimately coupled to enzymatic turnover in AK(eco). Here, we probe the open to closed conformational equilibrium in the absence of bound substrate with NMR spectroscopy and molecular dynamics simulations. The conformational equilibrium in absence of substrate and, in turn, the turnover number can be modulated with mutational- and osmolyte-driven perturbations. Removal of one hydrogen bond between the ATP and AMP binding subdomains results in a population shift toward the open conformation and a resulting increase of k(cat). Addition of the osmolyte TMAO to AK(eco) results in population shift toward the closed conformation and a significant reduction of k(cat). The Michaelis constants (K(M)) scale with the change in k(cat), which follows from the influence of the population of the closed conformation for substrate binding affinity. Hence, k(cat) and K(M) are mutually dependent, and in the case of AK(eco), any perturbation that modulates k(cat) is mirrored with a proportional response in K(M). Thus, our results demonstrate that the equilibrium constant of a pre-existing conformational equilibrium directly affects enzymatic catalysis. From an evolutionary perspective, our findings suggest that, for AK(eco), there exists ample flexibility to obtain a specificity constant (k(cat)/K(M)) that commensurate with the exerted cellular selective pressure.

  4. Effect of everolimus on pre-existing atherosclerosis in LDL-receptor deficient mice.

    PubMed

    Beutner, Frank; Brendel, Désiré; Teupser, Daniel; Sass, Kristina; Baber, Ronny; Mueller, Marc; Ceglarek, Uta; Thiery, Joachim

    2012-06-01

    Proliferation signal inhibitors/mTOR-inhibitors have been shown to reduce de novo development of hypercholesterolemic atherosclerosis in animal models. However, their effect on pre-existing atherosclerosis has not yet been studied. Feeding LDL-R-KO mice a high cholesterol diet for 12 weeks resulted in formation of moderate fibroatheroma (induction phase). Sixty mice received either everolimus (1 or 5 mg/kg) or no everolimus for further 12 weeks (treatment phase). Everolimus significantly enhanced hypercholesterolemia (plasma cholesterol +45%, p<0.001). Atherosclerosis progressed obstructively in treated and non-treated mice. Everolimus (5 mg/kg) tended to reduced progression in aortic root lesions (0.28±0.02 vs. 0.33±0.03 mm(2), p=ns) and brachiocephalic lesions (0.044±0.006 vs. 0.066±0.012 mm(2), p=ns) but without significance. Everolimus (5mg/kg) resulted in an arrest of CD68 positive plaque area (p=0.03) and nearly halved CD68 fraction (p=0.05) in aortic root lesions but not in brachiocephalic lesions. Taken together, despite a trend to reduced progression and inflammatory cell content there was less conclusive net effect of everolimus treatment than expected. A higher potential of everolimus in the treatment of atherosclerosis might be obscured by its concomitant hypercholesterolemia. Considering stronger effects in previous studies we suggest that everolimus might exert more potent anti-atherogenic properties in earlier stages of atherogenesis than in advanced atherosclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Belatacept-versus Cyclosporine-Based Immunosuppression in Renal Transplant Recipients with Pre-existing Diabetes

    PubMed Central

    Neumayer, Hans H.; Reyes-Acevedo, Rafael; Bresnahan, Barbara; Florman, Sander; Vitko, Stefan; Heifets, Michael; Xing, Jun; Thomas, Dolca; Vincenti, Flavio

    2011-01-01

    Summary Background and objectives Renal transplant recipients with pre-existing diabetes (PD) have reduced graft survival and increased risk of mortality and ischemic heart disease compared with nondiabetic transplant recipients. To assess the effect of belatacept in this high-risk group, we evaluated outcomes of the subpopulation with PD from previously published BENEFIT and BENEFIT-EXT trials. Design, setting, participants, & measurements A post hoc analysis evaluated pooled data from BENEFIT (living donors or standard criteria donors) and BENEFIT-EXT (extended criteria donors). Patients were randomized to receive cyclosporine or a more intensive (MI) or less intensive (LI) belatacept regimen. Results Of 1209 intent-to-treat patients, 336 had PD. At 12 months, the belatacept LI arm demonstrated a numerically higher rate of patients surviving with a functioning graft (90.4% MI [103 of 114], 92.8% LI [90 of 97], and 80.8% cyclosporine [101 of 125]), and fewer serious adverse events than cyclosporine or MI patients. Three cases of posttransplant lymphoproliferative disorder were reported in LI patients, one involving the central nervous system. Higher rates (% [95% confidence interval]: 22.8% MI [15.1 to 30.5]; 20.6% LI [12.6 to 28.7]; 14.4% cyclosporine (8.2 to 20.6]) and grades of acute rejection were observed with belatacept. Measured GFR (ml/min per 1.73 m2, 59.8 MI; 62.5 LI; 45.4 cyclosporine), and cardiovascular risk profile were better for belatacept versus cyclosporine. Conclusions In post hoc analysis of patients with PD, patient/graft survival and renal function at 12 months were numerically higher with belatacept versus cyclosporine, but not statistically significant. Further study is necessary to confirm the benefits belatacept may provide in these patients. PMID:21921152

  6. Streptococcus constellatus-associated pyoderma in a dog.

    PubMed

    De Martino, Luisa; Nizza, Sandra; de Martinis, Claudio; Foglia Manzillo, Valentina; Iovane, Valentina; Paciello, Orlando; Pagnini, Ugo

    2012-03-01

    This report describes a case of chronic and deep pyodermitis in a 4-year-old male dog with a 3-month skin problems history that had been treated unsuccessfully with fluoroquinolone therapy, prescribed by a private medical veterinary practice, without an early diagnosis. Microbiological examination and antimicrobial susceptibility testing were performed in our laboratory (Faculty of Veterinary Medicine) and a diagnosis of Streptococcus constellatus-associated pyoderma in the dog was made. A new antimicrobial treatment, with tetracyclines, was designed after the definitive diagnosis and antimicrobial susceptibility testing performed by the Kirby-Bauer disc diffusion method. The dog remained free of clinical illness at completion of therapy. To our knowledge, this is the first case of a canine pyoderma caused by S. constellatus, a commensal organism which may also cause pyogenic infections. Furthermore, this study confirms that a fluoroquinolone represents a poor empirical choice for initial therapy of canine pyoderma.

  7. Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis

    PubMed Central

    Lim, Sharon; Hosaka, Kayoko; Nakamura, Masaki; Cao, Yihai

    2016-01-01

    Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth. PMID:27203675

  8. 3D Numerical Modeling of the Propagation of Hydraulic Fracture at Its Intersection with Natural (Pre-existing) Fracture

    NASA Astrophysics Data System (ADS)

    Dehghan, Ali Naghi; Goshtasbi, Kamran; Ahangari, Kaveh; Jin, Yan; Bahmani, Aram

    2017-02-01

    A variety of 3D numerical models were developed based on hydraulic fracture experiments to simulate the propagation of hydraulic fracture at its intersection with natural (pre-existing) fracture. Since the interaction between hydraulic and pre-existing fractures is a key condition that causes complex fracture patterns, the extended finite element method was employed in ABAQUS software to simulate the problem. The propagation of hydraulic fracture in a fractured medium was modeled in two horizontal differential stresses (Δ σ) of 5e6 and 10e6 Pa considering different strike and dip angles of pre-existing fracture. The rate of energy release was calculated in the directions of hydraulic and pre-existing fractures (G_{{frac}} /G_{{rock}}) at their intersection point to determine the fracture behavior. Opening and crossing were two dominant fracture behaviors during the hydraulic and pre-existing fracture interaction at low and high differential stress conditions, respectively. The results of numerical studies were compared with those of experimental models, showing a good agreement between the two to validate the accuracy of the models. Besides the horizontal differential stress, strike and dip angles of the natural (pre-existing) fracture, the key finding of this research was the significant effect of the energy release rate on the propagation behavior of the hydraulic fracture. This effect was more prominent under the influence of strike and dip angles, as well as differential stress. The obtained results can be used to predict and interpret the generation of complex hydraulic fracture patterns in field conditions.

  9. Does pre-existing L5-S1 degeneration affect outcomes after isolated L4-5 fusion for spondylolisthesis?

    PubMed

    Choi, Kyung-Chul; Shim, Hyeong-Ki; Kim, Jin-Sung; Lee, Sang-Ho

    2015-03-26

    Concerns have been raised regarding residual symptoms of caudal segment (L5-S1) degeneration that may affect clinical outcomes or require additional surgery after isolated L4-5 fusion, especially if there is pre-existing L5-S1 degeneration. This study aimed to evaluate the L5-S1 segment after minimally invasive lumbar interbody fusion at the L4-5 segment, as well as the influence of pre-existing L5-S1 degeneration on radiologic and clinical outcomes. This retrospective study evaluated patients with isthmic spondylolisthesis and degenerative spondylolisthesis who underwent mini-open anterior lumbar interbody fusion with percutaneous pedicle screw fixation (PSF) or minimally invasive transforaminal interbody fusion with PSF at the L4-5 segment. The minimum follow-up period was 7 years, and radiographic evaluations were conducted via magnetic resonance imaging, computed tomography, and plain radiography at the 5-year follow-up. Clinical outcomes were assessed using the Visual Analog Score, Oswestry Disability Index, and surgical satisfaction rate. Patients were divided into two groups, those with and without pre-existing L5-S1 degeneration, and their final outcomes and incidence of radiographic and clinical adjacent segment disease (ASD) were compared. Among 70 patients who underwent the procedures at our institution, 12 (17.1%) were lost to follow-up. Therefore, this study evaluated 58 patients, with a mean follow-up period of 9.4 ± 2.1 years. Among these patients, 22 patients had pre-existing L5-S1 degeneration, while 36 patients did not have pre-existing L5-S1 segmental degeneration. There were no significant differences in the clinical outcomes at the final follow-up when the two groups were compared. However, radiographic ASD at L5-S1 occurred in seven patients (12.1%), clinical ASD at L5-S1 occurred in three patients (5.2%), and one patient (1.7%) required surgery. In the group with pre-existing degeneration, L5-S1 degeneration was radiographically

  10. A new Glacier Inventory of the Antarctic Peninsula as compiled from pre-existing Datasets

    NASA Astrophysics Data System (ADS)

    Huber, J.; Cook, A. J.; Paul, F.; Zemp, M.

    2016-12-01

    The glaciers on the Antarctic Peninsula (AP) potentially make a large contribution to sea level rise. However, this contribution was difficult to estimate, as no complete glacier inventory (outlines, attributes, separation from the ice sheet) was available so far. This work fills the gap and presents a new glacier inventory of the AP north of 70° S based on digitally combining pre-existing datasets with GIS techniques. Rock outcrops are removed from the glacier basin outlines of Cook et al. (2014) by digital intersection with the latest layer of the Antarctic Digital Database (Burton-Johnson et al. 2016). Glacier-specific topographic parameters (e.g. mean elevation, slope and aspect) as well as hypsometry have been calculated from the DEM of Cook et al. (2012). We also assigned connectivity levels to all glaciers following the concept by Rastner et al. (2012). Moreover, the bedrock dataset of Huss and Farinotti (2014) enabled us to add ice thickness and volume for each glacier. The new inventory is available from the GLIMS database and consists of 1589 glaciers covering an area of 95273 km2, slightly more than the 90000 km2 covered by glaciers surrounding the Greenland Ice Sheet. The total ice volume is 34590 km3 of which 1/3 is below sea level. The hypsometric curve has a bimodal shape due to the special topography of the AP consisting mainly of ice caps with outlet glaciers. Most of the glacierized area is located at 200-500 m a.s.l. with a secondary maximum at 1500-1900 m. About 63% of the area is drained by marine-terminating glaciers and ice shelf tributary glaciers cover 35% of the area. This combination results in a high sensitivity of the glaciers to climate change for several reasons: (1) only slightly rising equilibrium line altitudes would expose huge additional areas to ablation, (2) rising ocean temperatures increase melting of marine terminating glaciers, and (3) ice shelves have a buttressing effect on their feeding glaciers and their collapse would

  11. Identification and Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to Castration-Resistant Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    propagation. Lgr5+ intestinal stem cells can initiate and maintain murine intestinal adenomas (6, 7). In mouse models of skin cancer, hair follicle bulge...AWARD NUMBER: W81XWH-13-1-0470 TITLE: Identification and Targeting of Candidate Pre... Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to 5a. CONTRACT NUMBER Castration-Resistant Prostate Cancer 5b

  12. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Coordination with Medicaid, CHIP, the Basic Health....345 Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition..., CHIP, and the BHP, if a BHP is operating in the service area of the Exchange, as are necessary to...

  13. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Coordination with Medicaid, CHIP, the Basic Health....345 Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition..., CHIP, and the BHP as are necessary to fulfill the requirements of this subpart and provide copies of...

  14. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Coordination with Medicaid, CHIP, the Basic Health....345 Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition..., CHIP, and the BHP, if a BHP is operating in the service area of the Exchange, as are necessary to...

  15. Parasitic folds with wrong vergence: How pre-existing geometrical asymmetries can be inherited during multilayer buckle folding

    NASA Astrophysics Data System (ADS)

    Frehner, Marcel; Schmid, Timothy

    2016-06-01

    Parasitic folds are typical structures in geological multilayer folds; they are characterized by a small wavelength and are situated within folds with larger wavelength. Parasitic folds exhibit a characteristic asymmetry (or vergence) reflecting their structural relationship to the larger-scale fold. Here we investigate if a pre-existing geometrical asymmetry (e.g., from sedimentary structures or folds from a previous tectonic event) can be inherited during buckle folding to form parasitic folds with wrong vergence. We conduct 2D finite-element simulations of multilayer folding using Newtonian materials. The applied model setup comprises a thin layer exhibiting the pre-existing geometrical asymmetry sandwiched between two thicker layers, all intercalated with a lower-viscosity matrix and subjected to layer-parallel shortening. When the two outer thick layers buckle and amplify, two processes work against the asymmetry: layer-perpendicular flattening between the two thick layers and the rotational component of flexural flow folding. Both processes promote de-amplification and unfolding of the pre-existing asymmetry. We discuss how the efficiency of de-amplification is controlled by the larger-scale fold amplification and conclude that pre-existing asymmetries that are open and/or exhibit low amplitude are prone to de-amplification and may disappear during buckling of the multilayer system. Large-amplitude and/or tight to isoclinal folds may be inherited and develop type 3 fold interference patterns.

  16. The epidemiology of post-traumatic stress disorder in Norway: trauma characteristics and pre-existing psychiatric disorders.

    PubMed

    Lassemo, Eva; Sandanger, Inger; Nygård, Jan F; Sørgaard, Knut W

    2017-01-01

    The prevalence of PTSD differs by gender. Pre-existing psychiatric disorders and different traumas experienced by men and women may explain this. The aims of this study were to assess (1) incidence and prevalence of exposure to traumatic events and PTSD, (2) the effect of pre-existing psychiatric disorders prior to trauma on the risk for PTSD, and (3) the effect the characteristics of trauma have on the risk for PTSD. All stratified by gender. CIDI was used to obtain diagnoses at the interview stage and retrospectively for the general population N = 1634. The incidence for trauma was 466 and 641 per 100,000 PYs for women and men, respectively. The incidence of PTSD was 88 and 31 per 100,000 PYs. Twelve month and lifetime prevalence of PTSD was 1.7 and 4.3 %, respectively, for women, and 1.0 and 1.4 %, respectively, for men. Pre-existing psychiatric disorders were risk factors for PTSD, but only in women. Premeditated traumas were more harmful. Gender differences were observed regarding traumatic exposure and in the nature of traumas experienced and incidences of PTSD. Men experienced more traumas and less PTSD. Pre-existing psychiatric disorders were found to be risk factors for subsequent PTSD in women. However, while trauma happens to most, it only rarely leads to PTSD, and the most harmful traumas were premeditated ones. Primary prevention of PTSD is thus feasible, although secondary preventive efforts should be gender-specific.

  17. Is pre-existing dementia an independent predictor of outcome after stroke? A propensity score-matched analysis.

    PubMed

    Saposnik, Gustavo; Kapral, Moira K; Cote, Robert; Rochon, Paula A; Wang, Julie; Raptis, Stavroula; Mamdani, Muhammad; Black, Sandra E

    2012-11-01

    With an aging population, patients are increasingly likely to present with stroke and pre-existing dementia, which may lead to greater death and disability. The aim of this work was to assess the risk of all-cause mortality and poor functional outcomes after ischemic stroke in patients with and without pre-existing dementia. We conducted a multicenter cohort study of all patients presenting to 12 tertiary care institutions participating in the Registry of the Canadian Stroke Network (RCSN) with a first ischemic stroke between 2003 and 2008. Individuals with pre-existing dementia were matched using propensity-score methods with patients without dementia during their index hospitalization based on the following characteristics: age (within 3 years), sex, stroke severity, stroke subtype (lacunar vs. non-lacunar), level of consciousness, vascular risk factors, dysphagia, glucose and creatinine on admission, Charlson index, residence prior to hospitalization (home vs. other), pre-admission dependency, hospital arrival via ambulance, admission to stroke unit, thrombolysis, and palliative care. A propensity score for all-cause mortality and clinical outcomes was developed. Registry of the Canadian Stroke Network (RCSN) and Registered Persons Database (RPDB). The primary outcome was all-cause mortality at 30 days. Secondary outcomes included mortality at discharge and at 1 year, disability at discharge (modified Rankin scale ≥ 3), medical complications (pneumonia), and discharge disposition. A subgroup analysis assessing the risk of intracerebral hemorrhage among those receiving thrombolysis was also conducted. We matched 877 patients with an acute ischemic stroke and pre-existing dementia to 877 stroke patients without dementia. Patients were well matched. The mean age was 82 years and 58 % were women. Mortality at discharge, 30 days, and 1 year after stroke was similar in patients with and without dementia [for mortality at discharge RR 0.88 [95 % confidence interval

  18. High blood glucose independent of pre-existing diabetic status predicts mortality in patients initiating peritoneal dialysis therapy.

    PubMed

    Chung, Sung Hee; Han, Dong Cheol; Noh, Hyunjin; Jeon, Jin Seok; Kwon, Soon Hyo; Lindholm, Bengt; Lee, Hi Bahl

    2015-06-01

    Poor glycemic control associates with increased mortality in diabetic (DM) dialysis patients, but it is less well established whether high blood glucose (BG) independent of pre-existing diabetic status associates with mortality in dialysis patients. We assessed factors affecting BG at the start of peritoneal dialysis (PD) and its mortality-predictive impact in Korean PD patients. In 174 PD patients (55 % males, 56 % DM), BG, nutritional status, comorbidity (CMD), and residual renal function (RRF) were assessed in conjunction with dialysis initiation. Determinants of BG and its association with mortality after a mean follow-up period of 30 ± 24 months were analyzed. On Cox proportional hazards analysis comprising all patients, old age, high CMD score, presence of protein energy wasting, and low serum albumin (Salb) concentration were independent predictors of mortality but not a high-BG level, while in patients without pre-existing diabetic status, high BG, together with old age and high CMD score, was an independent predictor of mortality. After adjustment for age, CMD score, and Salb, the risk ratio for mortality increased by 12 % per 1 mg/dL increase in BG in the non-DM patients. Patient survival in patients without pre-existing diabetic status with high BG did not differ from DM patients, but the survival of patients with high BG was significantly lower than in patients with low BG. In patients without pre-existing diabetic status, in multiple regression analysis, high BG at initiation of PD associated with high age, high body mass index, and low RRF. High blood glucose at initiation of PD associated with an increased mortality risk in PD patients without pre-existing diabetic status suggesting that blood glucose monitoring and surveillance of factors contributing to poor glycemic control are warranted in patients initiating PD therapy.

  19. Evaluation of the clinical efficacy of pradofloxacin tablets for the treatment of canine pyoderma.

    PubMed

    Restrepo, Christina; Ihrke, Peter J; White, Stephen D; Spiegel, Ian B; Affolter, Verena K

    2010-01-01

    A third-generation fluoroquinolone, pradofloxacin (PRA), is currently being developed to treat bacterial infections in dogs. The purpose of this study was to assess the clinical efficacy in 20 dogs affected with superficial and deep pyoderma. An initial aerobic skin culture was performed in dogs with superficial pyoderma; aerobic/anaerobic tissue culture was performed in dogs with deep pyoderma; and skin cytology and biopsies were obtained from all dogs. Pradofloxacin (approximately 3 mg/kg per os [PO]) was administered daily to all dogs. Clinical efficacy was recorded at 4 weeks for dogs with superficial pyoderma and at 3 and 6 weeks for dogs with deep pyoderma. At a mean dosage of 3.7 mg/kg PO once daily, PRA treatment resulted in an excellent to good clinical response within 3 to 6 weeks for all 20 dogs with superficial and deep pyoderma.

  20. Three-dimensional numerical analysis of magma transport through a pre-existing fracture in the crust

    NASA Astrophysics Data System (ADS)

    Chen, Zuan; Cheng, Xu; Huang, Xiaoge; Bai, Wuming; Jin, Zhi-He

    2014-05-01

    Magmas are transported through pre-existing fractures in many repeatedly erupting volcanoes. The study of this special process of magma transport is fundamentally important to understand the mechanisms and conditions of volcanic eruptions. In this paper, we numerically simulate the magma propagation process through a pre-existing vertical fracture in the crust by using the combined finite difference method (FDM), finite element method (FEM) and discontinuous deformation analysis (DDA) approach. FDM is used to analyze magma flow in the pre-existing fracture, FEM is used to calculate the opening of the fracture during magma intrusion, and DDA is used to deal with the contact of the closed fracture surfaces. Both two-dimensional (2D) and three-dimensional (3D) examples are presented. Parametric studies are carried out to investigate the influence of various physical and geometric parameters on the magma transport in the pre-existing fracture. We have considered magma chamber depth ranging from 7 km to 10 km under the crust surface, magma viscosity ranging from 2 × 10-2 to 2 × 10-7 MPa s, and the density difference between the magma and host rock ranging from 300 to 700 kg/m3. The numerical results indicate that (1) the fluid pressure p varies gradually along the depth, (2) the shape of the magma body during propagation is like a torch bar and its width ranges from 2 m to 4 m approximately in the 3D case and 10 m to 50 m in the 2D case for the same physical parameters used, (3) the crust surface around the pre-existing fracture begins to increase on both sides of the fracture, forms a trough between them, then gradually uplifts during the transport of the magma, and finally takes the shape of a crater when the magma reaches the surface. We have also examined the influence of physical and geometric parameters on the minimum overpressure for magma transport in the 3D case. The numerical results show that our numerical technique presented in this paper is an effective

  1. Avoiding the requirement for pre-existing optical contact during picosecond laser glass-to-glass welding.

    PubMed

    Chen, Jianyong; Carter, Richard M; Thomson, Robert R; Hand, Duncan P

    2015-07-13

    Previous reports of ultrafast laser welding of glass-to-glass have indicated that a pre-existing optical contact (or very close to) between the parts to be joined is essential. In this paper, the capability of picosecond laser welding to bridge micron-scale gaps is investigated, and successful welding, without cracking, of two glasses with a pre-existing gap of 3 µm is demonstrated. It is shown that the maximum gap that can be welded is not significantly affected by welding speeds, but is strongly dependent on the laser power and focal position relative to the interface between the materials. Five distinct types of material modification were observed over a range of different powers and surface separations, and a mechanism is proposed to explain the observations.

  2. The experience of altered states of consciousness in shamanic ritual: the role of pre-existing beliefs and affective factors.

    PubMed

    Polito, Vince; Langdon, Robyn; Brown, Jac

    2010-12-01

    Much attention has been paid recently to the role of anomalous experiences in the aetiology of certain types of psychopathology, e.g. in the formation of delusions. We examine, instead, the top-down influence of pre-existing beliefs and affective factors in shaping an individual's characterisation of anomalous sensory experiences. Specifically we investigated the effects of paranormal beliefs and alexithymia in determining the intensity and quality of an altered state of consciousness (ASC). Fifty five participants took part in a sweat lodge ceremony, a traditional shamanic ritual which was unfamiliar to them. Participants reported significant alterations in their state of consciousness, quantified using the 'APZ' questionnaire, a standardized measure of ASC experience. Participants endorsing paranormal beliefs compatible with shamanic mythology, and those showing difficulty identifying feelings scored higher on positive dimensions of ASC experience. Our findings demonstrate that variation in an individual's characterisation of anomalous experiences is nuanced by pre-existing beliefs and affective factors.

  3. The pre-existing population of 5S rRNA effects p53 stabilization during ribosome biogenesis inhibition

    PubMed Central

    Onofrillo, Carmine; Galbiati, Alice; Montanaro, Lorenzo; Derenzini, Massimo

    2017-01-01

    Pre-ribosomal complex RPL5/RPL11/5S rRNA (5S RNP) is considered the central MDM2 inhibitory complex that control p53 stabilization during ribosome biogenesis inhibition. Despite its role is well defined, the dynamic of 5S RNP assembly still requires further characterization. In the present work, we report that MDM2 inhibition is dependent by a pre-existing population of 5S rRNA. PMID:28032591

  4. The pre-existing population of 5S rRNA effects p53 stabilization during ribosome biogenesis inhibition.

    PubMed

    Onofrillo, Carmine; Galbiati, Alice; Montanaro, Lorenzo; Derenzini, Massimo

    2017-01-17

    Pre-ribosomal complex RPL5/RPL11/5S rRNA (5S RNP) is considered the central MDM2 inhibitory complex that control p53 stabilization during ribosome biogenesis inhibition. Despite its role is well defined, the dynamic of 5S RNP assembly still requires further characterization. In the present work, we report that MDM2 inhibition is dependent by a pre-existing population of 5S rRNA.

  5. Impact of acute malaria on pre-existing antibodies to viral and vaccine antigens in mice and humans.

    PubMed

    Banga, Simran; Coursen, Jill D; Portugal, Silvia; Tran, Tuan M; Hancox, Lisa; Ongoiba, Aissata; Traore, Boubacar; Doumbo, Ogobara K; Huang, Chiung-Yu; Harty, John T; Crompton, Peter D

    2015-01-01

    Vaccine-induced immunity depends on long-lived plasma cells (LLPCs) that maintain antibody levels. A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies--raising concerns that malaria may compromise pre-existing vaccine responses. We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge. We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B) before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season. On average, vaccine-specific IgG did not decrease following acute malaria. However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies.

  6. Pre-existing tolerance shapes the outcome of mucosal allergen sensitization in a murine model of asthma.

    PubMed

    Chapman, Timothy J; Emo, Jason A; Knowlden, Sara A; Rezaee, Fariba; Georas, Steve N

    2013-10-15

    Recent published studies have highlighted the complexity of the immune response to allergens, and the various asthma phenotypes that arise as a result. Although the interplay of regulatory and effector immune cells responding to allergen would seem to dictate the nature of the asthmatic response, little is known regarding how tolerance versus reactivity to allergen occurs in the lung. The vast majority of mouse models study allergen encounter in naive animals, and therefore exclude the possibility that previous encounters with allergen may influence future sensitization. To address this, we studied sensitization to the model allergen OVA in mice in the context of pre-existing tolerance to OVA. Allergen sensitization by either systemic administration of OVA with aluminum hydroxide or mucosal administration of OVA with low-dose LPS was suppressed in tolerized animals. However, higher doses of LPS induced a mixed Th2 and Th17 response to OVA in both naive and tolerized mice. Of interest, tolerized mice had more pronounced Th17-type inflammation than did naive mice receiving the same sensitization, suggesting pre-existing tolerance altered the inflammatory phenotype. These data show that a pre-existing tolerogenic immune response to allergen can affect subsequent sensitization in the lung. These findings have potential significance for understanding late-onset disease in individuals with severe asthma.

  7. Pre-existing Tolerance Shapes the Outcome of Mucosal Allergen Sensitization in a Murine Model of Asthma

    PubMed Central

    Chapman, Timothy J; Emo, Jason A; Knowlden, Sara A; Rezaee, Fariba; Georas, Steve N

    2013-01-01

    Recent published studies have highlighted the complexity of the immune response to allergens, and the various asthma phenotypes that arise as a result. While the interplay of regulatory and effector immune cells responding to allergen would seem to dictate the nature of the asthmatic response, little is known as to how tolerance versus reactivity to allergen occurs in the lung. The vast majority of mouse models study allergen encounter in naïve animals, and therefore exclude the possibility that previous encounters with allergen may influence future sensitization. To address this, we studied sensitization to the model allergen OVA in mice in the context of pre-existing tolerance to OVA. Allergen sensitization by either systemic administration of OVA with aluminum hydroxide or mucosal administration of OVA with low-dose lipopolysaccharide (LPS) was suppressed in tolerized animals. However, higher doses of LPS induced a mixed Th2 and Th17 response to OVA in both naïve and tolerized mice. Interestingly, tolerized mice had more pronounced Th17 type inflammation than naïve mice receiving the same sensitization, suggesting pre-existing tolerance altered the inflammatory phenotype. These data show that a pre-existing tolerogenic immune response to allergen can impact subsequent sensitization in the lung. These findings have potential significance in understanding late-onset disease in severe asthmatics. PMID:24038084

  8. Modelling of structural complexity in sedimentary basins: The role of pre-existing faults in thrust tectonics

    NASA Astrophysics Data System (ADS)

    Sassi, W.; Colletta, B.; Balé, P.; Paquereau, T.

    1993-11-01

    Analogue and numerical models have been used to study the role of pre-existing faults in compressive regimes. From a theoretical point of view, reactivation is mainly controlled by fault attitude, stress regime and frictional properties of fault planes. In scaled-down sandbox experiments, precut faults are introduced in the homogeneous granular media with a nylon wire which is forced through the sand cake producing a thin planar disturbed zone. Systematic experiments of thrust inversion with various dips and strikes of such planar discontinuities have been modelled. Comparison of experimental results with theoretical diagrams indicate that disturbed zones have a friction angle which is 10-20% lower than the homogeneous sand and that the compressive regime in the sandbox has a shape factor close to 0.4. The static analysis of fault reactivation is in accordance with the experimental observations except for pre-existing faults dipping at very low angle. However, numerical modelling using the Udec code shows that low-angle faults can be reactivated as a result of stress concentration in the lower part of the fault. In addition, sandbox experiments indicate that in thrust systems, reactivation of pre-existing faults is not only dependent on their attitude but also on their spacing and location relative to the thrust system.

  9. Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents.

    PubMed

    Attarbaschi, Andishe; Carraro, Elisa; Abla, Oussama; Barzilai-Birenboim, Shlomit; Bomken, Simon; Brugieres, Laurence; Bubanska, Eva; Burkhardt, Birgit; Chiang, Alan K S; Csoka, Monika; Fedorova, Alina; Jazbec, Janez; Kabickova, Edita; Krenova, Zdenka; Lazic, Jelena; Loeffen, Jan; Mann, Georg; Niggli, Felix; Miakova, Natalia; Osumi, Tomoo; Ronceray, Leila; Uyttebroeck, Anne; Williams, Denise; Woessmann, Wilhelm; Wrobel, Grazyna; Pillon, Marta

    2016-12-01

    Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%±4% and 51%±4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%±4% and 24%±4%, respectively. Ten-year incidence of second malignancy was 24%±5% and 7-year overall survival of the 21 patients with a second malignancy was 41%±11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation. Copyright© Ferrata

  10. The effectiveness of systemic antimicrobial treatment in canine superficial and deep pyoderma: a systematic review.

    PubMed

    Summers, Jennifer F; Brodbelt, David C; Forsythe, Peter J; Loeffler, Anette; Hendricks, Anke

    2012-08-01

    To identify and evaluate existing evidence for the effectiveness of systemic antimicrobial treatments for naturally occurring superficial and deep canine pyoderma. Electronic searches of PubMed, MEDLINE and CAB Direct were carried out (25 May 2011) without date or language restrictions. Proceedings of ESVD/ECVD, AAVD/ACVD, NAVDF and WCVD annual congresses were searched. Unpublished studies were sought via the Veterinary Dermatology discussion list and Veterinary Information Network. Seventeen full-length, peer-reviewed controlled trials reporting clinical outcomes of systemic antimicrobial treatment for canine pyoderma were identified. Outcomes specific to superficial or deep pyoderma were reported in nine and five studies, respectively. Five studies reported outcomes only for nondifferentiated pyoderma depth. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. A good level of evidence was identified supporting the high efficacy of subcutaneously injected cefovecin in superficial pyoderma and for oral amoxicillin-clavulanic acid in deep pyoderma. A fair level of evidence was identified for moderate to high efficacy of oral amoxicillin-clavulanic acid, clindamycin, cefadroxil, trimethoprim-sulphamethoxazole and sulfadimethoxine-ormetoprim in superficial pyoderma and oral pradofloxacin, oral cefadroxil and subcutaneously injected cefovecin in deep pyoderma. Eleven trials reported observations of adverse effects in treated pyoderma cases by intervention group; four dogs were withdrawn owing to the severity of adverse effects. There is a need for greater numbers of adequately sized, blinded, randomized controlled trials evaluating systemic antimicrobial interventions for canine pyoderma. Improved differentiation between superficial and deep pyoderma in outcome reporting, outcome measure standardization and association of outcomes with causative bacterial species and their resistance patterns are required. © 2012 The Authors

  11. Prevalence of methicillin-resistant staphylococci in canine pyoderma cases in primary care veterinary practices in Canada: A preliminary study

    PubMed Central

    Joffe, Daniel; Goulding, Fiona; Langelier, Ken; Magyar, Gabor; McCurdy, Les; Milstein, Moe; Nielsen, Kia; Villemaire, Stephanie

    2015-01-01

    Pyoderma in dogs is most commonly caused by Staphylococcus spp., and significant emergence of methicillin resistance in staphylococcal pyoderma has been reported. This preliminary study of the prevalence of methicillin resistance in canine pyoderma cases in Canadian primary care veterinary practices revealed that methicillin-resistant Staphylococcus spp. were present in 12.1% of 149 staphylococcal positive skin culture cases. PMID:26483585

  12. Prevalence of methicillin-resistant staphylococci in canine pyoderma cases in primary care veterinary practices in Canada: A preliminary study.

    PubMed

    Joffe, Daniel; Goulding, Fiona; Langelier, Ken; Magyar, Gabor; McCurdy, Les; Milstein, Moe; Nielsen, Kia; Villemaire, Stephanie

    2015-10-01

    Pyoderma in dogs is most commonly caused by Staphylococcus spp., and significant emergence of methicillin resistance in staphylococcal pyoderma has been reported. This preliminary study of the prevalence of methicillin resistance in canine pyoderma cases in Canadian primary care veterinary practices revealed that methicillin-resistant Staphylococcus spp. were present in 12.1% of 149 staphylococcal positive skin culture cases.

  13. Skin disorders, including pyoderma, scabies, and tinea infections.

    PubMed

    Andrews, Ross M; McCarthy, James; Carapetis, Jonathan R; Currie, Bart J

    2009-12-01

    Pyoderma, scabies, and tinea are common childhood skin disorders too often considered to be merely of nuisance value. More than 111 million children are believed to have pyoderma, with many also co-infected with scabies, tinea, or both. These skin disorders cannot be differentiated by ethnicity or socioeconomic status but, in high-prevalence areas, poverty and overcrowded living conditions are important underlying social determinants. Each is transmitted primarily through direct skin-to-skin contact. For many Indigenous children, these skin conditions are part of everyday life. Although rarely directly resulting in hospitalization or death, there is a high and largely unmet demand for effective management at the primary health-care level, particularly for pyoderma and scabies. Despite particularly high prevalence in some settings, treatment is not sought for many children, and when sought, the clinical benefit from such consultations is variable. The lack of standard, evidence-based recommendations is of much concern. The current evidence base for clinical diagnosis and treatment of these common childhood skin disorders is highlighted.

  14. Dose assessment of 2% chlorhexidine acetate for canine superficial pyoderma.

    PubMed

    Murayama, Nobuo; Terada, Yuri; Okuaki, Mio; Nagata, Masahiko

    2011-10-01

    The dose of 2% chlorhexidine acetate (2CA; Nolvasan(®) Surgical Scrub; Fort Dodge Animal Health, Fort Dodge, IA, USA) for canine superficial pyoderma was evaluated. The first trial compared three doses (group 1, 57 mL/m(2) body surface area; group 2, 29 mL/m(2) body surface area; and group 3, 19 mL/m(2) body surface area) in a randomized, double-blind, controlled fashion. Twenty-seven dogs with superficial pyoderma were treated with 2CA at the allocated doses every 2 days for 1 week. The owners and investigators subjectively evaluated the dogs, and investigators scored skin lesions, including erythema, papules/pustules, alopecia and scales, on a 0-4 scale. There were no significant differences in response between the treatment groups. The second trial established a practical dose-measuring method for 2CA. Sixty-eight owners were asked to apply 2CA on their palm in an amount corresponding to a Japanese ¥500 coin, 26.5 mm in diameter. This yielded an average dose of 0.90±0.40 mL. Mathematically, the doses used in groups 1, 2 and 3 can be represented as one coin per approximately one-, two- and three-hand-sized lesions, respectively. The results therefore suggest that owners instructed to apply one coin of the product per two-hand-sized areas of superficial pyoderma would use the range of doses evaluated in this trial.

  15. Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats.

    PubMed

    Vollbrecht, Peter J; Nobile, Cameron W; Chadderdon, Aaron M; Jutkiewicz, Emily M; Ferrario, Carrie R

    2015-12-01

    Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals.

  16. Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris.

    PubMed

    Zhou, Aifen; Hillesland, Kristina L; He, Zhili; Schackwitz, Wendy; Tu, Qichao; Zane, Grant M; Ma, Qiao; Qu, Yuanyuan; Stahl, David A; Wall, Judy D; Hazen, Terry C; Fields, Matthew W; Arkin, Adam P; Zhou, Jizhong

    2015-11-01

    To investigate the genetic basis of microbial evolutionary adaptation to salt (NaCl) stress, populations of Desulfovibrio vulgaris Hildenborough (DvH), a sulfate-reducing bacterium important for the biogeochemical cycling of sulfur, carbon and nitrogen, and potentially the bioremediation of toxic heavy metals and radionuclides, were propagated under salt stress or non-stress conditions for 1200 generations. Whole-genome sequencing revealed 11 mutations in salt stress-evolved clone ES9-11 and 14 mutations in non-stress-evolved clone EC3-10. Whole-population sequencing data suggested the rapid selective sweep of the pre-existing polymorphisms under salt stress within the first 100 generations and the slow fixation of new mutations. Population genotyping data demonstrated that the rapid selective sweep of pre-existing polymorphisms was common in salt stress-evolved populations. In contrast, the selection of pre-existing polymorphisms was largely random in EC populations. Consistently, at 100 generations, stress-evolved population ES9 showed improved salt tolerance, namely increased growth rate (2.0-fold), higher biomass yield (1.8-fold) and shorter lag phase (0.7-fold) under higher salinity conditions. The beneficial nature of several mutations was confirmed by site-directed mutagenesis. All four tested mutations contributed to the shortened lag phases under higher salinity condition. In particular, compared with the salt tolerance improvement in ES9-11, a mutation in a histidine kinase protein gene lytS contributed 27% of the growth rate increase and 23% of the biomass yield increase while a mutation in hypothetical gene DVU2472 contributed 24% of the biomass yield increase. Our results suggested that a few beneficial mutations could lead to dramatic improvements in salt tolerance.

  17. Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-FVIII immunity

    PubMed Central

    Kuether, E. L.; Schroeder, J. A.; Fahs, S. A.; Cooley, B. C.; Chen, Y.; Montgomery, R. R.; Wilcox, D. A.; Shi, Q.

    2012-01-01

    Summary Background The development of inhibitory antibodies, referred to as inhibitors, against exogenous FVIII in a significant subset of patients with hemophilia A remains a persistent challenge to the efficacy of protein replacement therapy. Our previous studies using the transgenic approach provided proof-of-principle that platelet-specific expression could be successful for treating hemophilia A in the presence of inhibitory antibodies. Objective To investigate a clinically translatable approach for platelet gene therapy of hemophilia A with pre-existing inhibitors. Methods Platelet-FVIII expression in pre-immunized FVIIInull mice was introduced by transplantation of lentivirus-transduced bone marrow or enriched hematopoietic stem cells. FVIII expression was determined by a chromogenic assay. The transgene copy number per cell was quantitated by real time PCR. Inhibitor titer was measured by Bethesda assay. Phenotypic correction was assessed by the tail clipping assay and an electrolytic-induced venous injury model. Integration sites were analyzed by LAM-PCR. Results Therapeutic levels of platelet-FVIII expression were sustained long-term without evoking an anti-FVIII memory response in the transduced pre-immunized recipients. The tail clip survival test and the electrolytic injury model confirmed that hemostasis was improved in the treated animals. Sequential bone marrow transplants showed sustained platelet-FVIII expression resulting in phenotypic correction in pre-immunized secondary and tertiary recipients. Conclusions Lentivirus-mediated platelet-specific gene transfer improves hemostasis in hemophilic A mice with pre-existing inhibitors, indicating that this approach may be a promising strategy for gene therapy of hemophilia A even in the high-risk setting of pre-existing inhibitory antibodies. PMID:22632092

  18. New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

    PubMed

    Méry-Bossard, L; Bagny, K; Chaby, G; Khemis, A; Maccari, F; Marotte, H; Perrot, J L; Reguiai, Z; Sigal, M L; Avenel-Audran, M; Boyé, T; Grasland, A; Gillard, J; Jullien, D; Toussirot, E

    2017-01-01

    The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo. © 2016 European Academy of Dermatology and Venereology.

  19. Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris

    PubMed Central

    Zhou, Aifen; Hillesland, Kristina L; He, Zhili; Schackwitz, Wendy; Tu, Qichao; Zane, Grant M; Ma, Qiao; Qu, Yuanyuan; Stahl, David A; Wall, Judy D; Hazen, Terry C; Fields, Matthew W; Arkin, Adam P; Zhou, Jizhong

    2015-01-01

    To investigate the genetic basis of microbial evolutionary adaptation to salt (NaCl) stress, populations of Desulfovibrio vulgaris Hildenborough (DvH), a sulfate-reducing bacterium important for the biogeochemical cycling of sulfur, carbon and nitrogen, and potentially the bioremediation of toxic heavy metals and radionuclides, were propagated under salt stress or non-stress conditions for 1200 generations. Whole-genome sequencing revealed 11 mutations in salt stress-evolved clone ES9-11 and 14 mutations in non-stress-evolved clone EC3-10. Whole-population sequencing data suggested the rapid selective sweep of the pre-existing polymorphisms under salt stress within the first 100 generations and the slow fixation of new mutations. Population genotyping data demonstrated that the rapid selective sweep of pre-existing polymorphisms was common in salt stress-evolved populations. In contrast, the selection of pre-existing polymorphisms was largely random in EC populations. Consistently, at 100 generations, stress-evolved population ES9 showed improved salt tolerance, namely increased growth rate (2.0-fold), higher biomass yield (1.8-fold) and shorter lag phase (0.7-fold) under higher salinity conditions. The beneficial nature of several mutations was confirmed by site-directed mutagenesis. All four tested mutations contributed to the shortened lag phases under higher salinity condition. In particular, compared with the salt tolerance improvement in ES9-11, a mutation in a histidine kinase protein gene lytS contributed 27% of the growth rate increase and 23% of the biomass yield increase while a mutation in hypothetical gene DVU2472 contributed 24% of the biomass yield increase. Our results suggested that a few beneficial mutations could lead to dramatic improvements in salt tolerance. PMID:25848870

  20. Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats

    PubMed Central

    Vollbrecht, Peter J.; Nobile, Cameron W.; Chadderdon, Aaron M.; Jutkiewicz, Emily M.; Ferrario, Carrie R.

    2015-01-01

    Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel “junk-food” diet on the development of obesity and metabolic dysfunction, 2) over-consumption of “junk-food” in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, “junk-food” diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals. PMID:26423787

  1. Application of a national administrative case definition for the identification of pre-existing diabetes mellitus in pregnancy.

    PubMed

    Allen, V M; Dodds, L; Spencer, A; Cummings, E A; MacDonald, N; Kephart, G

    2012-06-01

    Accurate ascertainment of pregnant women with pre-existing diabetes allows for the comprehensive surveillance of maternal and neonatal outcomes associated with this chronic disease. To determine the accuracy of case definitions for pre-existing diabetes mellitus when applied to a pregnant population, a cohort of women who were pregnant in Nova Scotia, Canada, between 1991 and 2003 was obtained from a population-based provincial perinatal database, the Nova Scotia Atlee Perinatal Database (NSAPD). Person-level data from administrative databases using hospital discharge abstract data and outpatient physician services data were linked to this cohort. Various algorithms for defining diabetes mellitus from the administrative data, including the algorithm suggested by the National Diabetes Surveillance System (NDSS), were compared to a reference standard definition from the NSAPD. Validation of the NDSS case definition applied to this pregnant population demonstrated a sensitivity of 87% and a positive predictive value (PPV) of 66.4%. Use of ICD-9 and ICD-10 diagnostic codes among hospitalizations with diabetes mellitus in pregnancy showed important increases in sensitivity and PPV, especially for those pregnancies delivered in tertiary centres. In this population, pregnancy-related administrative data from the hospitalization database alone appear to be a more accurate data source for identifying pre-existing diabetes than applying the NDSS case definition, particularly when pregnant women are delivered in a tertiary hospital. Although the NDSS definition of diabetes performs reasonably well compared to a reference standard definition of diabetes, using this definition for evaluating maternal and perinatal outcomes associated with diabetes in pregnancy will result in a certain degree of misclassification and, therefore, biased estimates of outcomes.

  2. The role of pre-existing thrust ramps on the evolution of a differently oriented thrust systems

    NASA Astrophysics Data System (ADS)

    Bonini, Lorenzo; Pini, Gian Andrea; Ponton, Maurizio; Del Ben, Anna

    2017-04-01

    In the accretionary wedges, as well as in fold-and-thrust belts, shortening is mostly accommodated by fault-related folding. This kind of structures are sensitive both to internal factors such as the mechanical characteristics of the rocks involved in contractional processes, and to external ones such as erosion or syn-kinematics sedimentation. Notwithstanding such diversity, the resulting geometries are commonly composed by faults with flat and ramp trajectory and their related folds. The above mentioned factors may directly affect both the geometry and the kinematics of a fault-related folding, for instance, the location, the number, and the frictional properties of weak horizons lead the location and the extent of the flat portion of the thrust systems. The mechanical properties of the rocks involved in the contractional phase impacts on the location and geometry of the thrust ramp. Thus, the stratigraphic and tectonic architecture of an area is central to predict or study the evolution of a contractional system. Among different factors, we select to test the role of pre-existing thrust ramp on the subsequent evolution on differently oriented thrust ramp. As a method we use analogue modeling and as an analogue material we use wet clay (kaolin). We reproduce different setups varying the initial orientation of the pre-existing thrust ramp with respect to the new ramp that we force to nucleate in the same region of the experiment box. The tested angles vary from 0°, i.e. the two ramps are parallel, to 90°, i.e. the two ramps are perpendicular. Our results show that the angle between the two systems directly impact on the degree of development of new ramps. When the angle between new and pre-existing thrust ramps is low, e.g. <30°, the reactivation of the pre-existing ramp prevail on the development of a new ramp. Conversely, high angles promote the development of new thrust ramps optimally oriented with respect to the imposed stress field. Our results are

  3. Pharmacokinetics of micafungin in patients with pre-existing liver dysfunction: A safe option for treating invasive fungal infections.

    PubMed

    Luque, Sonia; Campillo, Nuria; Álvarez-Lerma, Francisco; Ferrández, Olivia; Horcajada, Juan Pablo; Grau, Santiago

    2016-12-01

    In this prospective observational study performed in 12 hospitalized patients with proven or suspected invasive fungal infection treated for a mean of 14 days with micafungin (MCF), 8 of whom with pre-existing liver function impairment, plasma levels of MCF at steady state were not correlated with liver function tests at the beginning of treatment. Liver function remained stable or even improved in all patients, except in one in which MCF was discontinued due to liver toxicity. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  4. Survival Patterns in Patients With Hodgkin's Lymphoma With a Pre-Existing Hospital Discharge Diagnosis of Autoimmune Disease

    PubMed Central

    Landgren, Ola; Pfeiffer, Ruth M.; Kristinsson, Sigurdur Y.; Björkholm, Magnus

    2010-01-01

    Purpose Autoimmune diseases (AIs) are associated with elevated risk for Hodgkin's lymphoma (HL); however, information on the interplay of AIs and HL on survival is sparse. Patients and Methods We evaluated survival patterns for 7,414 patients with HL in relation to a pre-existing hospital discharge diagnosis of an AI. We also assessed survival patterns in relation to a prior AI diagnosis among 29,240 population-based matched controls. Results Among female patients with HL with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 46.0% (63.3%) and 41.0% (51.9%); for males, the corresponding numbers were 48.5% (59.2%) and 43.6% (51.5%), respectively (P < .001). Among female controls with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 79.1% (90.2%) and 67.2% (83.3%); for males, the corresponding numbers were 82.5% (90.3%) and 68.6% (81.6%), respectively (P < .001). Female patients with HL with (v those without) a pre-existing AI had a 1.8-fold (range, 1.3- to 2.4-fold) increased relative risk of dying at 5 years of follow-up; for males, the corresponding excess relative risk of dying was 1.7-fold (range, 1.3- to 2.2-fold). Conclusion Patients with HL have an overall excellent outcome from treatment but also pose some of the most complex challenges of cancer survivorship due to many late effects (eg, second malignancies, thyroid disease, cardiovascular disease, and altered reproductive and sexual function). Our finding that patients with HL with a hospital discharge diagnosis of an AI have a substantially higher risk of dying, emphasizes that underlying chronic diseases, such as AIs, should be high of the list of survivorship concerns for clinicians that treat HL. PMID:20940191

  5. A Clinico-Bacteriological Study of Pyodermas at a Tertiary Health Center in Southwest Rajasthan

    PubMed Central

    Singh, Ajit; Gupta, Lalit Kumar; Khare, Ashok Kumar; Mittal, Asit; Kuldeep, CM; Balai, Manisha

    2015-01-01

    Background: The spectrum of pyoderma changes constantly, and so does the antibiotic susceptibility pattern. Aims: This study was done to assess the magnitude and clinical patterns of pyodermas, their causative micro-organisms, and the antibiotic susceptibility patterns. Materials and Methods: Five hundred consecutive, clinically diagnosed and untreated cases of pyoderma, attending the Dermatology OPD of RNT Medical College and MB Government Hospital, Udaipur, from October 2010 to September 2011 were the subjects of this study. A detailed clinical examination, and relevant investigations including bacterial culture and sensitivity, were carried out and recorded. Statistical Analysis: For statistical analysis of data, the software ‘EPI-INFO Version 6’ was used, and Chi-square (χ2) test was applied. Results: Of 19576 cases attending skin OPD during the study period, pyoderma was seen in 500 patients; the incidence being 2.55%. Males outnumbered females. The highest number of cases (109; 21.8%) was observed in 1st decade. Lower extremities were the commonest site of predilection. Primary pyodermas outnumbered secondary pyodermas. Furuncle (136; 27.2%) and infectious eczematoid dermatitis (62; 12.4%) were the commonest entities among primary and secondary pyoderma respectively. Staphylococcus aureus was the commonest causative agent in both primary and secondary pyoderma. It showed high susceptibility to amoxycillin + sulbactam, aminoglycosides and cefoperazone, moderate susceptibility to linezolid, while low susceptibility to fluoroquinolones and cephalexin. Conclusion: Such studies help to assess the changing trend of bacterial infections, their causative organisms and antibiotic susceptibility pattern. PMID:26538696

  6. Efficacy of anti-staphylococcal protein P128 for the treatment of canine pyoderma: potential applications.

    PubMed

    Junjappa, Raghu Patil; Desai, Srividya Narayanamurthy; Roy, Panchali; Narasimhaswamy, Nagalakshmi; Raj, Juliet Roshini Mohan; Durgaiah, Murali; Vipra, Aradhana; Bhat, Udaya Ravi; Satyanarayana, Smitha Komarla; Shankara, Nandini; Basingi, Suneelkumar Muragesh; Bhat, Jagadeesh Janardhan; Hariharan, Sukumar; Sriram, Bharathi; Padmanabhan, Sriram

    2013-09-01

    In this study, we demonstrate the antibacterial activity of P128 on Staphylococcus isolates responsible for canine pyoderma. Eighty seven swabs were collected from dogs suffering from pyoderma and subjected to antibiotic sensitivity test and 46 Staphylococcus strains were isolated and characterized. In-vitro antimicrobial susceptibility testing with P128 was done by Minimum Inhibitory Concentration (MIC) method as per CLSI guidelines. All the Staphylococci isolated from the dogs with pyoderma, although showed resistance to various antibiotics tested, were lysed by P128. Clinical efficacy of P128 was examined in 17 dogs with pyoderma by application of the P128 hydrogel twice daily for 8 days and the results indicated complete healing of all the lesions of all the dogs under treatment. Under the conditions of this study, P128 was found to be a potent convenient proteinaceous drug for the treatment of staphylococcal pyoderma in dogs.

  7. Dermatophyte abscesses caused by Trichophyton rubrum in a patient without pre-existing superficial dermatophytosis: a case report.

    PubMed

    Kim, Si-Hyun; Jo, Ik Hyun; Kang, Jun; Joo, Sun Young; Choi, Jung-Hyun

    2016-06-17

    Trichophyton usually causes a superficial skin infection, affecting the outermost layer of the epidermis, the stratum corneum. In immunocompromised patients, deeper invasion into the dermis and even severe systemic infection with distant organ involvement can occur. Most cases of deeper dermal dermatophytosis described in the literature so far involved pre-existing superficial dermatophytosis. We report a 68-year-old woman presented to our clinic with a 3-month history of palpable nodules on the right ankle without pre-existing superficial dermatophytosis. Magnetic resonance imaging showed multiple, well-demarcated, cystic lesions around the lateral malleolus, located in the subcutaneous or dermal layers. The sizes varied from 0.5 cm to 4 cm in diameter. The patient underwent complete excision of the lesions. Fungal culture yielded Trichophyton rubrum on Sabouraud dextrose agar. Histopathology showed organizing abscesses with degenerated fungal hyphae. After the 12-week oral itraconazole therapy, the lesions were completely resolved. Dermatophytes should be considered as a possible cause of deep soft tissue abscesses in immunocompromised patients, even though there is no superficial dermatophytosis lesion.

  8. Sports Dermatology: Part 1 of 2 Traumatic or Mechanical Injuries, Inflammatory Conditions, and Exacerbations of Pre-existing Conditions

    PubMed Central

    Sivek, Rachel; Marciniak, Brian

    2015-01-01

    Competitive athletes endure extreme bodily stress when participating in sports-related activities. An athlete’s skin is particularly susceptible to a wide array of repetitive physical and environmental stressors that challenge the skin’s protective function. Many unique dermatoses are well-known to the serious athlete due to countless hours of intense physical training, but are frequently unrecognized by many healthcare professionals. Sports dermatology is a distinctive, budding field of dermatology that focuses on dermatoses frequently encountered in athletes. Athletic skin problems are notoriously infectious in nature due to the inherent environment of close-contact physical activity. Nonetheless, other skin conditions can manifest or worsen with recurring mechanical or traumatic injury or exposure to environmental hazards. Additionally, sports-related activities may exacerbate other pre-existing dermatological conditions that may possibly be unknown to the athlete or clinician. The objective of this two-part review is to arm the astute physician with the fundamental knowledge of the range of dermatological conditions distinct to the competitive athlete. Knowledge of these cutaneous conditions in the context of specific sporting events will permit the clinician to manage these unique patients most effectively. Part one will focus on traumatic or mechanical injuries, inflammatory conditions, and exacerbations of pre-existing conditions frequently seen in athletes. PMID:26060516

  9. Sports Dermatology: Part 1 of 2 Traumatic or Mechanical Injuries, Inflammatory Conditions, and Exacerbations of Pre-existing Conditions.

    PubMed

    Emer, Jason; Sivek, Rachel; Marciniak, Brian

    2015-04-01

    Competitive athletes endure extreme bodily stress when participating in sports-related activities. An athlete's skin is particularly susceptible to a wide array of repetitive physical and environmental stressors that challenge the skin's protective function. Many unique dermatoses are well-known to the serious athlete due to countless hours of intense physical training, but are frequently unrecognized by many healthcare professionals. Sports dermatology is a distinctive, budding field of dermatology that focuses on dermatoses frequently encountered in athletes. Athletic skin problems are notoriously infectious in nature due to the inherent environment of close-contact physical activity. Nonetheless, other skin conditions can manifest or worsen with recurring mechanical or traumatic injury or exposure to environmental hazards. Additionally, sports-related activities may exacerbate other pre-existing dermatological conditions that may possibly be unknown to the athlete or clinician. The objective of this two-part review is to arm the astute physician with the fundamental knowledge of the range of dermatological conditions distinct to the competitive athlete. Knowledge of these cutaneous conditions in the context of specific sporting events will permit the clinician to manage these unique patients most effectively. Part one will focus on traumatic or mechanical injuries, inflammatory conditions, and exacerbations of pre-existing conditions frequently seen in athletes.

  10. Pre-existing Renal Disease Promotes Sepsis-induced Acute Kidney Injury and Worsens Sepsis Outcome via Multiple Pathways

    PubMed Central

    Doi, Kent; Leelahavanichkul, Asada; Hu, Xuzhen; Sidransky, Karen L.; Qin, Yan; Eisner, Christoph; Schnermann, Jurgen; Yuen, Peter S. T.; Star, Robert A.

    2008-01-01

    Patients with chronic kidney disease (CKD) are at significantly higher risk of death from sepsis, although the mechanism by which CKD increases mortality has not been investigated. We established a mouse two-stage model of pre-existing renal disease with subsequent sepsis by combining folic acid (FA) injection and sub-lethal cecal ligation and puncture (CLP) surgery. Mice were injected with FA then made septic (FA-CLP) or were injected with vehicle then made septic (Veh-CLP). FA-CLP mice had significantly higher mortality than Veh-CLP mice. Sepsis increased serum creatinine in the FA-CLP but not in the Veh-CLP group. FA-CLP mice had more severe septic shock and significantly increased vascular permeability, plasma vascular endothelial growth factor (VEGF), bacteremia, serum IL-10 and splenocyte apoptosis compared to Veh-CLP. To evaluate the contribution of vascular and immunological dysfunction, we treated FA-CLP mice with soluble Flt-1 and chloroquine. Mice treated with combination therapy showed a significant improvement in kidney injury, hemodynamics, and survival. In conclusion, the sequential FA-CLP model mimics human sepsis that is frequently complicated with pre-existing conditions including CKD. This animal model would be useful to evaluate preventative and therapeutic strategies under conditions more typical of human sepsis. PMID:18633340

  11. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice

    PubMed Central

    Annoni, Andrea; Cantore, Alessio; Della Valle, Patrizia; Goudy, Kevin; Akbarpour, Mahzad; Russo, Fabio; Bartolaccini, Sara; D'Angelo, Armando; Roncarolo, Maria Grazia; Naldini, Luigi

    2013-01-01

    A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50–100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients. PMID:24106222

  12. Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors.

    PubMed

    Wang, Lili; Calcedo, Roberto; Bell, Peter; Lin, Jianping; Grant, Rebecca L; Siegel, Don L; Wilson, James M

    2011-11-01

    Vectors based on the primate-derived adeno-associated virus serotype 8 (AAV8) are being evaluated in preclinical and clinical models. Natural infections with related AAVs activate memory B cells that produce antibodies capable of modulating the efficacy and safety of the vector. We have evaluated the biology of AAV8 gene transfer in macaque liver, with a focus on assessing the impact of pre-existing humoral immunity. Twenty-one macaques with various levels of AAV neutralizing antibody (NAb) were injected intravenously with AAV8 vector expressing green fluorescent protein. Pre-existing antibody titers in excess of 1:10 substantially diminished hepatocyte transduction that, in the absence of NAbs, was highly efficient. Vector-specific NAb diminished liver deposition of genomes and unexpectedly increased genome distribution to the spleen. The majority of animals showed high-level and stable sequestration of vector capsid protein by follicular dendritic cells of splenic germinal centers. These studies illustrate how natural immunity to a virus that is related to a vector can impact the efficacy and potential safety of in vivo gene therapy. We propose to use the in vitro transduction inhibition assay to evaluate research subjects before gene therapy and to preclude from systemic AAV8 trials those that have titers in excess of 1:10.

  13. Effects of pre-existing discontinuities on the residual strength of rock mass - Insight from a discrete element method simulation

    NASA Astrophysics Data System (ADS)

    Gao, F. Q.; Kang, H. P.

    2016-04-01

    When rock failure is unavoidable, the designer of engineering structures must know and account for the residual strength of the rock mass. This is particularly relevant in underground coal mine openings. Pre-existing discontinuities play an important role in the mechanical behavior of rock masses and thus it is important to understand the effects of such pre-existing discontinuities on the residual strength. For this purpose, the present study demonstrates a numerical analysis using a discrete element method simulation. The numerical results indicate that fracture intensity has no significant influence on the residual strength of jointed rock masses, independent of confining conditions. As confining pressures increase, both peak and residual strengths increase, with residual strength increasing at a faster rate. The finding was further demonstrated by analyzing documented laboratory compressive test data from a variety of rocks along with field data from coal pillars. A comprehensive interpretation of the finding was conducted using a cohesion-weakening-friction-strengthening (CWFS) model. The effect of rock bolts on rock mass strength was also evaluated by using a discrete element method model which suggested that rock bolts can significantly increases residual strength but have limited effect on increasing the peak strength of rock masses.

  14. Pre-existing Pulmonary Diseases and Survival in Patients With Stage-dependent Lung Adenocarcinoma: A STROBE-compliant Article.

    PubMed

    Jian, Zhi-Hong; Huang, Jing-Yang; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Wu, Ming-Fang; Liaw, Yung-Po

    2016-03-01

    Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival.Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan-Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma.A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10-2.58), 1.48 (95% CI, 1.14-1.93), and 1.27 (95% CI, 1.08-1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00-1.99) in women with stage I + II and 1.14 (95% CI, 1.04-1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12-1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12-1.63) for COPD + TB, 1.28 (95% CI, 1.01-1.63) for TB, and 1.15 (95%CI, 1.04-1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72-17.71) for asthma + COPD + TB.Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality.

  15. Comparison of maternal morbidity and medical costs during pregnancy and delivery between patients with gestational diabetes and patients with pre-existing diabetes

    PubMed Central

    Son, K H; Lim, N-K; Lee, J-W; Cho, M-C; Park, H-Y

    2015-01-01

    Aims To evaluate the effects of gestational diabetes and pre-existing diabetes on maternal morbidity and medical costs, using data from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Methods Delivery cases in 2010, 2011 and 2012 (459 842, 442 225 and 380 431 deliveries) were extracted from the Health Insurance Review and Assessment Service database. The complications and medical costs were compared among the following three pregnancy groups: normal, gestational diabetes and pre-existing diabetes. Results Although, the rates of pre-existing diabetes did not fluctuate (2.5, 2.4 and 2.7%) throughout the study, the rate of gestational diabetes steadily increased (4.6, 6.2 and 8.0%). Furthermore, the rates of pre-existing diabetes and gestational diabetes increased in conjunction with maternal age, pre-existing hypertension and cases of multiple pregnancy. The risk of pregnancy-induced hypertension, urinary tract infections, premature delivery, liver disease and chronic renal disease were greater in the gestational diabetes and pre-existing diabetes groups than in the normal group. The risk of venous thromboembolism, antepartum haemorrhage, shoulder dystocia and placenta disorder were greater in the pre-existing diabetes group, but not the gestational diabetes group, compared with the normal group. The medical costs associated with delivery, the costs during pregnancy and the number of in-hospital days for the subjects in the pre-existing diabetes group were the highest among the three groups. Conclusions The study showed that the rates of pre-existing diabetes and gestational diabetes increased with maternal age at pregnancy and were associated with increases in medical costs and pregnancy-related complications. PMID:25472691

  16. [Surgical treatment of benign recurrent goiter with pre-existing unilateral recurrent laryngeal nerve paralysis--a report of experiences].

    PubMed

    Wasiak, J; Pohle, T

    1996-01-01

    Operations for recurrent goiter are considered to range among the most difficult procedures in thyroid surgery, because the risk of a permanent recurrent nerve palsy increases to 10 or 30%. In case of pre-existing unilateral lesion of the nerve the danger of bilateral paralysis of the vocal chord will become even larger. The results from 29 patients with an intracapsular resection (nearly total removement of the thyroid tissue without the preparation of the recurrent nerve) are presented and compared with those found in 4 patients with an extracapsular approach. All four patients, where the operation was performed extracapsularly, must be tracheotomized although the palsy did recover within 21 days till 14 months. After an intracapsular resection of the recurrence at the side of an intact nerve (29 patients) a tracheotomy had not been necessary.

  17. The effect of pre-existing islands on disruption mitigation in MHD simulations of DIII-D

    DOE PAGES

    Izzo, V. A.

    2017-02-27

    Locked-modes are the most likely cause of disruptions in ITER, so large islands are expected to be common when the ITER disruption mitigation system is deployed. MHD modeling of disruption mitigation by massive gas injection is carried out for DIII-D plasmas with stationary, pre-existing islands. Results show that the magnetic topology at the q=2 surface can affect the parallel spreading of injected impurities, and that, in particular, the break-up of large 2/1 islands into smaller 4/2 islands chains can favorably affect mitigation metrics. The direct imposition of a 4/2 mode is found to have similar results to the case inmore » which the 4/2 harmonic grows spontaneously.« less

  18. The Challenges and Future Considerations Regarding Pregnancy-related Outcomes in Women with Pre-Existing Diabetes

    PubMed Central

    Singh, Harsimran; Murphy, Helen R.; Hendrieckx, Christel; Ritterband, Lee; Speight, Jane

    2013-01-01

    Ineffective management of blood glucose levels during preconception and pregnancy hasbeen associated with severe maternal and fetal complications in women with pre-existing diabetes. Studies have demonstrated that preconception counseling and pre-pregnancy care can dramatically reduce these risks. However, pregnancy-related outcomes in women with diabetes continue to be less than ideal. This review highlights and discusses a variety of patient, provider, and organizational factors that can contribute to these suboptimal outcomes. Based on the findings of studies reviewed and authors' clinical and research experiences, recommendations have been proposed focusing on various aspects of care provided, including improved accessibility to effective preconception and pregnancy-related care and better organized clinic consultations that are sensitive to women's diabetes and pregnancy needs. PMID:24013963

  19. Aggravation of Pre-Existing Atrioventricular Block, Wenckebach Type, Provoked by Application of X-Ray Contrast Medium

    SciTech Connect

    Brodmann, Marianne Seinost, Gerald; Stark, Gerhard; Pilger, Ernst

    2006-12-15

    Background. Significant bradycardia followed by cardiac arrest related to single bolus administration of X-ray contrast medium into a peripheral artery has not, to our knowledge, been described in the literature. Methods and Results. While performing a percutaneous transluminal angioplasty of the left superficial femoral artery in a 68-year old patient with a pre-existing atrioventricular (AV) block, Wenckebach type, he developed an AV block III after a single bolus injection of intra-arterial X-ray contrast medium. Conclusion. We believe that application of contrast medium causes a transitory ischemia in the obstructed vessel and therefore elevation of endogenous adenosine. In the case of a previously damaged AV node this elevation of endogenous adenosine may be responsible for the development of a short period of third-degree AV block.

  20. The Association between Pre-existing Diabetes Mellitus and Pressure Ulcers in Patients Following Surgery: A Meta-analysis.

    PubMed

    Kang, Zhou-Qing; Zhai, Xiao-Jie

    2015-08-11

    Uncertainty exists about the role of diabetes in the development of surgery-related pressure ulcers. Therefore, we conducted a meta-analysis to explore the association between pre-existing diabetes mellitus and pressure ulcers among patients after surgery. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random effects models. Thirteen eligible studies of 2367 patients in total and 12,053 controls were included in the final analysis. Compared with patients without diabetes, the pooled odds ratio (OR) of the incidence of pressure ulcers in diabetic patients was 1.74 [95% confidence interval (CI) = 1.40-2.15, I(2 )= 51.1%]. Estimates by type of surgery suggested similar results in cardiac surgery [OR = 2.00, 95% CI = 1.42-2.82, I(2 )= 0%], in general surgery [OR = 1.75, 95% CI = 1.42-2.15, I(2 )= 0%], and in major lower limb amputations [OR = 1.65, 95% CI = 1.01-2.68, I(2 )= 0%] for diabetic patients versus non-diabetic controls. We did not find an increased incidence of pressure ulcers in diabetic patients undergoing hip surgery compared with non-diabetic controls [OR = 1.46, 95% CI = 0.62-3.47, I(2 )= 93.1%]. The excess risk of pressure ulcers associated with pre-existing diabetes was significantly higher in patients undergoing surgery, specifically in patients receiving cardiac surgery. Further studies should be conducted to examine these associations in other types of surgery.

  1. Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE.

    PubMed

    Bouchareychas, Laura; Pirault, John; Saint-Charles, Flora; Deswaerte, Virginie; Le Roy, Tiphaine; Jessup, Wendy; Giral, Philippe; Le Goff, Wilfried; Huby, Thierry; Gautier, Emmanuel L; Lesnik, Philippe

    2015-10-01

    Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown. We irradiated then transplanted into Apoe(-/-) or LDLr(-/-) recipient mice harbouring established atherosclerotic lesions, bone marrow cells from mice displaying enhanced macrophage survival through overexpression of the antiapoptotic gene hBcl-2 (Mø-hBcl2 Apoe(-/-) or Mø-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mø-hBcl2 mouse-derived bone marrow cells. In contrast, only LDLr(-/-) recipients showed a reduction in plasma cholesterol levels and in atherosclerotic lesions. The absence of significant reduction of plasma cholesterol levels in the context of apoE deficiency highlighted macrophage-derived apoE as key in both the regulation of plasma and tissue cholesterol levels and the progression of pre-existing lesion. Accordingly, hBcl2 expression in macrophages was associated with larger pools of Kupffer cells and Ly-6C(low) monocytes, both high producers of apoE. Additionally, increased Kupffer cells population was associated with improved clearance of apoptotic cells and modified lipoproteins. Collectively, these data show that promoting macrophage survival provides a supplemental source of apoE, which hinders pre-existing plaque progression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  2. Pre-existing smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions

    PubMed Central

    Yang, Pu; Hong, Michael S.; Fu, Chunhua; Schmit, Bradley M.; Su, Yunchao; Berceli, Scott A.; Jiang, Zhihua

    2015-01-01

    Background With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell-lineage composition across models, but the animal-to-animal difference has not attracted much attention though the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions. Methods The R26R+;Myh11-CreER+ and R26R+;Scl-CreER+ mice were utilized to attach LacZ tags to the pre-existing smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA). Results LacZ-tagged SMCs were physically relocated from media to neointima and changed to a de-differentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5–70% and 0–85%, with an average at low levels of 27% and 29% in CCA (n=15) and FA (n=15) lesions, respectively. Bone marrow cells, while able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Pre-existing ECs were located in the sub-endothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal-transition (EndoMT), however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n=7) and FA (n=7) lesions, respectively. ECs located on the luminal surface exhibited little evidence for EndoMT. Conclusion Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell-lineage composition. PMID:26387788

  3. Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT.

    PubMed

    Zhu, Hua; He, Jun; Cai, Junchao; Yuan, Xiaoni; Jiang, Hua; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Pan, Zhijuan; Terasaki, Paul I; Ding, Lixia; Chen, Jing

    2014-11-01

    Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse five-yr survival (78.6% vs. 100%, p = 0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT.

  4. Ecthyma gangrenosum: A manifestation of community-acquired Pseudomonas aeruginosa septicemia in three infants.

    PubMed

    Gargouri, L; Maaloul, I; Kamoun, T; Maalej, B; Safi, F; Majdoub, I; Hachicha, M; Mahfoudh, A

    2015-06-01

    Pseudomonas aeruginosa sepsis usually carries a high mortality rate in immunocompromised children. Ecthyma gangrenosum is a known cutaneous manifestation due mainly to Pseudomonas infection with or without septicemia. We describe clinical, biological, and therapeutic data. Of those children admitted to the pediatric intensive care unit, three pediatric cases of community-acquired P. aeruginosa septicemia associated with ecthyma gangrenosum were retrospectively reviewed. The three patients were aged 5 months, 9 months, and 1 year. Underlying hypogammaglobulinemia was detected in the oldest patient. Pseudomonas aeruginosa was isolated in all patients in blood and once in cultures of skin lesions and endotracheal aspirate. Two deaths occurred due to septic shock and multisystem organ failure despite numerous aggressive resuscitation attempts. P. aeruginosa sepsis should be treated as early as possible. Recognition of ecthyma gangrenosum allows early diagnosis and prescription of adequate antibiotic therapy without awaiting blood culture reports. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Nasal carriage of Staphylococcus schleiferi from healthy dogs and dogs with otitis, pyoderma or both.

    PubMed

    May, Elizabeth R; Kinyon, Joann M; Noxon, James O

    2012-12-07

    In veterinary medicine, Staphylococcus schleiferi was previously assumed to be an inhabitant of carnivore skin, however, more recently, it has been repeatedly documented in the literature as both an inhabitant and as a pathogen. In order to determine the frequency of nasal carriage, and the methicillin susceptibility pattern of S. schleiferi from healthy dogs as well as dogs with otitis and/or pyoderma, a prospective study including 24 dogs with healthy ears and skin, 27 dogs with healthy ears and pyoderma, 15 dogs with otitis without pyoderma and 20 dogs with both otitis and pyoderma was performed. Specimens were obtained and cultured and isolates were identified as S. schleiferi based on growth and biochemical characteristics. S. schleiferi was isolated from the nares of 1 healthy dog, 3 dogs with recurrent pyoderma, 2 dogs with recurrent otitis, and 1 dog with both recurrent otitis and pyoderma. One of the S. schleiferi isolates was methicillin resistant. Nasal carriage of S. schleiferi does occur in healthy dogs as well as dogs with otitis and pyoderma. Methicillin resistant and sensitive S. schleiferi can be found in the nares of dogs with diseased ears and skin. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. In vitro antimicrobial susceptibility of staphylococci isolated from canine pyoderma in Rio de Janeiro, Brazil

    PubMed Central

    Penna, B.; Varges, R.; Martins, G.M.; Martins, R.R.; Lilenbaum, W.

    2009-01-01

    The study aimed to determine the etiology and antimicrobial resistance of staphylococci isolated from canine pyoderma. Samples were obtained from dogs with pyoderma and isolates were identified by biochemical reactions and tested for susceptibility to 15 antimicrobials. Thirty nine staphylococci isolates were obtained, and S. pseudintermedius was the most frequent (47.4%). All isolates showed resistance to at least one drug and 77.1% were multiresistant. The most effective drug was oxacillin. The study reports the alarming antimicrobial resistance of Staphylococcus isolated from canine pyoderma samples. PMID:24031392

  7. Ecthyma gangrenosum and ecthyma-like lesions: review article.

    PubMed

    Vaiman, M; Lazarovitch, T; Heller, L; Lotan, G

    2015-04-01

    The generally accepted definition of ecthyma gangrenosum (EG) states that this condition is pathognomonic of Pseudomonas septicemia (Pseudomonas aeruginosa) and that it should usually be seen in immunocompromised patients, particularly those with underlying malignant disease. The cases described in the literature present a somewhat different picture. Our objective was to analyze this controversy. The review analyzes 167 cases of EG that were described in the literature from 1975 to 2014. All articles on EG cases with EG-specific tissue defect that had signs of general and/or local infection and skin necrosis were included and analyzed, whatever the etiology detected. Necrotic lesions of the skin diagnosed as EG have various microbiological etiology, can occur in immunocompetent or even healthy persons, and are not necessarily connected with septicemia. In published cases, P. aeruginosa was detected in 123 cases (73.65%); of them, there were only 72 cases (58.5%) with sepsis. Other bacterial etiology was detected in 29 cases (17.35%) and fungi were detected in 15 cases (9%). While the clinical picture of the disease and the treatment strategy remain the same, there is no need to invent two separate definitions for Pseudomonas and non-Pseudomonas cases. We suggest accepting a broader definition of EG.

  8. Evaluation of pre-existing antibody presence as a risk factor for posttreatment anti-drug antibody induction: analysis of human clinical study data for multiple biotherapeutics.

    PubMed

    Xue, Li; Rup, Bonita

    2013-07-01

    Biotherapeutic-reactive antibodies in treatment-naïve subjects (i.e., pre-existing antibodies) have been commonly detected during clinical immunogenicity assessments; however information on pre-existing antibody prevalence, physiological effects, and impact on posttreatment anti-drug antibody (ADA) induction remains limited. In this analysis, pre-existing antibody prevalence and impact on posttreatment ADA induction were determined using ADA data from 12 biotherapeutics analyzed in 32 clinical studies. Approximately half (58%) of the biotherapeutics were associated with some level of pre-existing antibodies and 67% of those were associated with posttreatment ADA induction. Across all studies, 5.6% of study subjects demonstrated presence of pre-existing antibodies, among which, 17% of the individual subjects had posttreatment increases in their ADA titers while 16% had decreased titers and 67% had no change in titers. However, in studies conducted in the rheumatoid arthritis (RA) population, 14.8% of RA patients were associated with pre-existing antibodies and 30% of those had posttreatment titer increases. The results suggest that in most study subjects, pre-existing antibodies pose a low risk for posttreatment ADA induction. That said, the high risk of induction implicated for RA patients, primarily observed in treatments evaluating novel antibody-based constructs, indicates that further understanding of the contribution of product and disease-specific factors is needed. Cross-industry efforts to collect and analyze a larger data set would enhance understanding of the prevalence, nature, and physiological consequences of pre-existing antibodies, better inform the immunogenicity risk profiles of products associated with these antibodies and lead to better fit-for-purpose immunogenicity management and mitigation strategies.

  9. Blastomycosis-Like Pyoderma- A Rare Case Report.

    PubMed

    Hongal, Amrita A; Gejje, Somashekar

    2016-10-01

    Blastomycosis-like pyoderma is a rare, cutaneous bacterial infection of skin, seen in malnourished individuals, in a poor state of health and manifests as vegetating skin lesions. It is an unusual tissue reaction possibly to bacterial infection, the most common organism being Staphylococcus aureus. This case report is of a 35-year-old male who presented with thick verrucous surfaced plaques and papules on trunk and extremities since 2 months. Investigations revealed anaemia with hypochromasia, neutrophilic leucocytosis, hypo-proteinemia and hypo-albuminemia with reversal of A/G ratio. Pathergy test was negative. Pus on Gram's stain showed plenty of pus cells, and negative for AFB and fungal stain. On culture of pus grew Coagulase negative staphylococcus species. Biopsy showed acanthosis of epidermis with moderate lymphocytic infiltrates in dermis and focally a few neutrophils and histiocytes. Patient fulfilled the criteria for diagnosis of blastomycosis like pyoderma viz., presentation of large verrucous plaques with pustules and ulcers with elevated border, histologically neutrophilic infiltration and growth of one pathogenic bacterium on culture. Patient responded to long-term cefotaxime therapy.

  10. Blastomycosis-Like Pyoderma- A Rare Case Report

    PubMed Central

    Gejje, Somashekar

    2016-01-01

    Blastomycosis-like pyoderma is a rare, cutaneous bacterial infection of skin, seen in malnourished individuals, in a poor state of health and manifests as vegetating skin lesions. It is an unusual tissue reaction possibly to bacterial infection, the most common organism being Staphylococcus aureus. This case report is of a 35-year-old male who presented with thick verrucous surfaced plaques and papules on trunk and extremities since 2 months. Investigations revealed anaemia with hypochromasia, neutrophilic leucocytosis, hypo-proteinemia and hypo-albuminemia with reversal of A/G ratio. Pathergy test was negative. Pus on Gram’s stain showed plenty of pus cells, and negative for AFB and fungal stain. On culture of pus grew Coagulase negative staphylococcus species. Biopsy showed acanthosis of epidermis with moderate lymphocytic infiltrates in dermis and focally a few neutrophils and histiocytes. Patient fulfilled the criteria for diagnosis of blastomycosis like pyoderma viz., presentation of large verrucous plaques with pustules and ulcers with elevated border, histologically neutrophilic infiltration and growth of one pathogenic bacterium on culture. Patient responded to long-term cefotaxime therapy. PMID:27891438

  11. The role of pre-existing tectonic structures and magma chamber shape on the geometry of resurgent blocks: Analogue models

    NASA Astrophysics Data System (ADS)

    Marotta, Enrica; de Vita, Sandro

    2014-02-01

    A set of analogue models has been carried out to understand the role of an asymmetric magma chamber on the resurgence-related deformation of a previously deformed crustal sector. The results are then compared with those of similar experiments, previously performed using a symmetric magma chamber. Two lines of experiments were performed to simulate resurgence in an area with a simple graben-like structure and resurgence in a caldera that collapsed within the previously generated graben-like structure. On the basis of commonly accepted scaling laws, we used dry-quartz sand to simulate the brittle behaviour of the crust and Newtonian silicone to simulate the ductile behaviour of the intruding magma. An asymmetric shape of the magma chamber was simulated by moulding the upper surface of the silicone. The resulting empty space was then filled with sand. The results of the asymmetric-resurgence experiments are similar to those obtained with symmetrically shaped silicone. In the sample with a simple graben-like structure, resurgence occurs through the formation of a discrete number of differentially displaced blocks. The most uplifted portion of the deformed depression floor is affected by newly formed, high-angle, inward-dipping reverse ring-faults. The least uplifted portion of the caldera is affected by normal faults with similar orientation, either newly formed or resulting from reactivation of the pre-existing graben faults. This asymmetric block resurgence is also observed in experiments performed with a previous caldera collapse. In this case, the caldera-collapse-related reverse ring-fault is completely erased along the shortened side, and enhances the effect of the extensional faults on the opposite side, so facilitating the intrusion of the silicone. The most uplifted sector, due to an asymmetrically shaped intrusion, is always in correspondence of the thickest overburden. These results suggest that the stress field induced by resurgence is likely dictated by

  12. Distribution of long-term Quaternary Deformation and Correlation with Pre-existing Tectonic Structures in the Central US

    NASA Astrophysics Data System (ADS)

    Magnani, M.; McIntosh, K. D.; Guo, L.; Hao, Y.

    2012-12-01

    control, possibly imposed by pre-existing structures, which are capable of concentrating strain and stress and localizing intraplate deformation. Surprisingly, no Quaternary deformation is detected across the buried Paleozoic Ouachita orogenic belt, indicating that under the same stress field, not all the pre-existing structures appear to be capable of focusing deformation.

  13. Blastomycosis-like pyoderma in a case of chronic myeloid leukaemia.

    PubMed Central

    Dutta, T. K.; James, J.; Baruah, M. C.; Ratnakar, C.

    1992-01-01

    Blastomycosis-like pyoderma, a rare skin lesion which may clinically resemble true blastomycosis, is seen in immuno-compromised individuals. We report one such case in chronic myeloid leukaemia. Images Figure 1 Figure 2 Figure 3 PMID:1630982

  14. Discovery of a pre-existing molecular filament associated with supernova remnant G127.1+0.5

    SciTech Connect

    Zhou, Xin; Yang, Ji; Fang, Min; Su, Yang

    2014-08-20

    We performed millimeter observations in CO lines toward the supernova remnant (SNR) G127.1+0.5. We found a molecular filament at 4-13 km s{sup –1} consisting of two distinct parts: a straight part coming out of the remnant region and a curved part in the remnant region. The curved part is coincides well with the bright SNR shell detected in 1420 MHz radio continuum and mid-infrared observations in the northeastern region. In addition, redshifted line wing broadening is found only in the curved part of the molecular filament, which indicates a physical interaction. These provide strong evidences, for the first time, to confirm the association between an SNR and a pre-existing long molecular filament. Multi-band observations in the northeastern remnant shell could be explained by the interaction between the remnant shock and the dense molecular filament. RADEX radiative transfer modeling of the quiet and shocked components yield physical conditions consistent with the passage of a non-dissociative J-type shock. We argue that the curved part of the filament is fully engulfed by the remnant's forward shock. A spatial correlation between aggregated young stellar objects (YSOs) and the adjacent molecular filament close to the SNR is also found, which could be related to the progenitor's activity.

  15. A Thermo-Hydro-Mechanical coupled Numerical modeling of Injection-induced seismicity on a pre-existing fault

    NASA Astrophysics Data System (ADS)

    Kim, Jongchan; Archer, Rosalind

    2017-04-01

    In terms of energy development (oil, gas and geothermal field) and environmental improvement (carbon dioxide sequestration), fluid injection into subsurface has been dramatically increased. As a side effect of these operations, a number of injection-induced seismic activities have also significantly risen. It is known that the main causes of induced seismicity are changes in local shear and normal stresses and pore pressure as well. This mechanism leads to increase in the probability of earthquake occurrence on permeable pre-existing fault zones predominantly. In this 2D fully coupled THM geothermal reservoir numerical simulation of injection-induced seismicity, we investigate the thermal, hydraulic and mechanical behavior of the fracture zone, considering a variety of 1) fault permeability, 2) injection rate and 3) injection temperature to identify major contributing parameters to induced seismic activity. We also calculate spatiotemporal variation of the Coulomb stress which is a combination of shear stress, normal stress and pore pressure and lastly forecast the seismicity rate on the fault zone by computing the seismic prediction model of Dieterich (1994).

  16. Influence of pre-existing topography on downflow lava discharge rates estimated from thermal infrared airborne data

    NASA Astrophysics Data System (ADS)

    Lombardo, V.

    2016-04-01

    Remote sensing thermal data of active lava flows allow the evaluation of effusion rates. This is made possible by a simple formula relating the lava effusion rate to the heat flux radiated per unit time from the surface of the flow. Due to the assumptions of the model, this formula implies that heat flux, surface temperature and lava temperature vary as a function of the flow thickness. These relationships, never verified or validated before, have been used by several authors as a proof of the weakness of the model. Here, multispectral infrared and visible imaging spectrometer (MIVIS) high spatial resolution (5-10 m) thermal data acquired during Etna's 2001 eruption were used to investigate downflow heat flux variations in the lava flow emitted from a vent located at 2100 m a.s.l. A high correlation between the downflow heat flux and the lava flow thickness (measured from a pre-existing digital elevation model) was found. Topography beneath the flow appears to play an important role both in lava emplacement mechanisms and flow dynamics. MIVIS-derived downflow effusion rates are consistent with the law of conservation of mass assessing the reliability of remote sensing techniques.

  17. Cross-reactive and pre-existing antibodies to therapeutic antibodies—Effects on treatment and immunogenicity

    PubMed Central

    van Schie, Karin A; Wolbink, Gerrit-Jan; Rispens, Theo

    2015-01-01

    The potential for immunogenicity is an ever-present concern during the development of biopharmaceuticals. Therapeutic antibodies occasionally elicit an antibody response in patients, which can result in loss of response or adverse effects. However, antibodies that bind a drug are sometimes found in pre-treatment serum samples, with the amount depending on drug, assay, and patient population. This review summarizes published data on pre-existing antibodies to therapeutic antibodies, including rheumatoid factors, anti-allotype antibodies, anti-hinge antibodies, and anti-glycan antibodies. Unlike anti-idiotype antibodies elicited by the drug, pre-formed antibodies in general appear to have little consequences during treatment. In the few cases where (potential) clinical consequences were encountered, antibodies were characterized and found to bind a distinct, unusual epitope of the therapeutic. Immunogenicity testing strategies should therefore always include a proper level of antibody characterization, especially when pre-formed antibodies are present. This minimizes false-positives, particularly due to rheumatoid factors, and helps to judge the potential threat in case a genuine pre-dose antibody reactivity is identified. PMID:25962087

  18. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice

    PubMed Central

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-01-01

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients. PMID:26482836

  19. Multi-epitope Models Explain How Pre-existing Antibodies Affect the Generation of Broadly Protective Responses to Influenza

    PubMed Central

    Zarnitsyna, Veronika I.; Lavine, Jennie; Ellebedy, Ali; Ahmed, Rafi; Antia, Rustom

    2016-01-01

    The development of next-generation influenza vaccines that elicit strain-transcendent immunity against both seasonal and pandemic viruses is a key public health goal. Targeting the evolutionarily conserved epitopes on the stem of influenza’s major surface molecule, hemagglutinin, is an appealing prospect, and novel vaccine formulations show promising results in animal model systems. However, studies in humans indicate that natural infection and vaccination result in limited boosting of antibodies to the stem of HA, and the level of stem-specific antibody elicited is insufficient to provide broad strain-transcendent immunity. Here, we use mathematical models of the humoral immune response to explore how pre-existing immunity affects the ability of vaccines to boost antibodies to the head and stem of HA in humans, and, in particular, how it leads to the apparent lack of boosting of broadly cross-reactive antibodies to the stem epitopes. We consider hypotheses where binding of antibody to an epitope: (i) results in more rapid clearance of the antigen; (ii) leads to the formation of antigen-antibody complexes which inhibit B cell activation through Fcγ receptor-mediated mechanism; and (iii) masks the epitope and prevents the stimulation and proliferation of specific B cells. We find that only epitope masking but not the former two mechanisms to be key in recapitulating patterns in data. We discuss the ramifications of our findings for the development of vaccines against both seasonal and pandemic influenza. PMID:27336297

  20. Pre-Existing Differences and Diet-Induced Alterations in Striatal Dopamine Systems of Obesity-Prone Rats

    PubMed Central

    Vollbrecht, Peter J.; Mabrouk, Omar S.; Nelson, Andrew D.; Kennedy, Robert T.; Ferrario, Carrie R.

    2016-01-01

    Objective Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2/D3 dopamine receptor-mediated transmission prior to and after consumption of “junk-foods” in obesity-prone and obesity-resistant rats. Methods Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2/D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Results Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. Conclusions These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. PMID:26847484

  1. Evolution of a fold-thrust belt deforming a unit with pre-existing linear asperities: Insights from analog models

    NASA Astrophysics Data System (ADS)

    Burberry, Caroline M.; Swiatlowski, Jerlyn L.

    2016-06-01

    Heterogeneity, whether geometric or rheologic, in crustal material undergoing compression affects the geometry of the structures produced. This study documents the thrust fault geometries produced when discrete linear asperities are introduced into an analog model, scaled to represent bulk upper crustal properties, and compressed. Varying obliquities of the asperities are used, relative to the imposed compression, and the resultant development of thrust fault traces and branch lines in map view is tracked. Once the model runs are completed, cross-sections are created and analyzed. The models show that asperities confined to the base layer promote the clustering of branch lines in the surface thrusts. Strong clustering in branch lines is also noted where several asperities are in close proximity or cross. Slight reverse-sense reactivation of asperities cut through the sedimentary sequence is noted in cross-section, where the asperity and the subsequent thrust belt interact. The model results are comparable to the situation in the Dinaric Alps, where pre-existing faults to the SW of the NE Adriatic Fault Zone contribute to the clustering of branch lines developed in the surface fold-thrust belt. These results can therefore be used to evaluate the evolution of other basement-involved fold-thrust belts worldwide.

  2. Observations on the automatic compensation of reflex gain on varying the pre-existing level of motor discharge in man.

    PubMed Central

    Matthews, P B

    1986-01-01

    The human stretch reflex is well known to show 'automatic gain compensation'; in other words, the electromyographic (e.m.g.) response evoked by a given disturbance increases progressively with the level of pre-existing voluntary activity, and so remains an approximately constant proportion of the background. Such behaviour has now been observed using vibration as the stimulus to Ia action and recording the reflexly developed force, in addition to the e.m.g. Inhibition was studied as well as excitation by vibrating the antagonist as well as the agonist, and found to be similarly regulated. The experiments were performed on the elbow flexors while they were contracting isometrically under voluntary drive. The vibration was either square-wave modulated at 5 Hz or delivered in bursts of one to five pulses. The latency of the e.m.g. responses produced by the latter was sufficiently short to show that gain compensation was a feature of spinal reflex action. In the Discussion, it is concluded that in principle 'automatic gain compensation' can be readily attributed to the known organization of the motoneurone pool. As the background force increases so does the number of active motoneurones available to be frequency-modulated by a given input, and the larger and stronger will be those motor units which are on the verge of recruitment or de-recruitment. PMID:3746703

  3. Transient left bundle branch block induced by left-sided cardiac catheterization in patients without pre-existing conduction abnormalities.

    PubMed

    Shimamoto, T; Nakata, Y; Sumiyoshi, M; Ogura, S; Takaya, J; Sakurai, H; Yamaguchi, H

    1998-02-01

    A traumatic left bundle branch block (LBBB) is uncommon in a patient with intact atrioventricular conduction. Three of our patients developed LBBB during a left-sided catheterization. Two patients suffered from angina pectoris and the other had an abdominal aneurysm. Two of them had a history of hypertension. None of the patients had ever shown any conduction abnormalities before the catheterization. The electrocardiogram just before the examination was normal in all 3 patients. LBBB was observed when a catheter was introduced into the left ventricle, and lasted 2--4 min without significant change in heart rates. Examination revealed no significant stenosis proximal to the first septal perforator and normal left ventricular contraction in all patients. One patient developed permanent LBBB 14 months later. Catheter-induced LBBB may occur easily with certain anatomical characteristics of the left bundle branch or the distal His bundle, with or without some concealed damage to the conduction system. It is important to keep this complication in mind and to pay adequate attention to patients' electrocardiograms as well as their angiographical findings, especially in those with pre-existing right bundle branch block.

  4. Interactions between X-ray induced transient defects and pre-existing damage precursors in DKDP crystals

    SciTech Connect

    Negres, R A; Saw, C K; Demos, S G

    2008-10-24

    Large-aperture laser systems, currently designed to achieve high energy densities at the target location (exceeding {approx} 10{sup 11} J/m{sup 3}), will enable studies of the physics of matter and radiation under extreme conditions. As a result, their optical components, such as the frequency conversion crystals (KDP/DKDP), may be exposed to X-rays and other ionizing radiation. This in turn may lead to a change in the damage performance of these materials as they may be affected by radiation-induced effects by either forming new damage initiation centers or interacting with the pre-existing damage initiating defects (so-called damage precursors). We present an experimental study on the laser-induced bulk damage performance at 355-nm of DKDP crystals following X-ray irradiation at room temperature. Results indicate that the damage performance of the material is affected by exposure to X-rays. We attribute this behavior to a change in the physical properties of the precursors which, in turn, affect their individual damage threshold.

  5. Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity

    PubMed Central

    Scherer, Erin M.; Smith, Robin A.; Simonich, Cassandra A.; Niyonzima, Nixon; Carter, Joseph J.; Galloway, Denise A.

    2014-01-01

    Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses. PMID:25330199

  6. Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

    PubMed

    Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

    2016-03-01

    Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

  7. The role of pre-existing disturbances in the effect of marine reserves on coastal ecosystems: a modelling approach.

    PubMed

    Savina, Marie; Condie, Scott A; Fulton, Elizabeth A

    2013-01-01

    We have used an end-to-end ecosystem model to explore responses over 30 years to coastal no-take reserves covering up to 6% of the fifty thousand square kilometres of continental shelf and slope off the coast of New South Wales (Australia). The model is based on the Atlantis framework, which includes a deterministic, spatially resolved three-dimensional biophysical model that tracks nutrient flows through key biological groups, as well as extraction by a range of fisheries. The model results support previous empirical studies in finding clear benefits of reserves to top predators such as sharks and rays throughout the region, while also showing how many of their major prey groups (including commercial species) experienced significant declines. It was found that the net impact of marine reserves was dependent on the pre-existing levels of disturbance (i.e. fishing pressure), and to a lesser extent on the size of the marine reserves. The high fishing scenario resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects on biomass and functional biodiversity. However, under the lower fishing pressure scenario, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives.

  8. Cross-reactive and pre-existing antibodies to therapeutic antibodies--Effects on treatment and immunogenicity.

    PubMed

    van Schie, Karin A; Wolbink, Gerrit-Jan; Rispens, Theo

    2015-01-01

    The potential for immunogenicity is an ever-present concern during the development of biopharmaceuticals. Therapeutic antibodies occasionally elicit an antibody response in patients, which can result in loss of response or adverse effects. However, antibodies that bind a drug are sometimes found in pre-treatment serum samples, with the amount depending on drug, assay, and patient population. This review summarizes published data on pre-existing antibodies to therapeutic antibodies, including rheumatoid factors, anti-allotype antibodies, anti-hinge antibodies, and anti-glycan antibodies. Unlike anti-idiotype antibodies elicited by the drug, pre-formed antibodies in general appear to have little consequences during treatment. In the few cases where (potential) clinical consequences were encountered, antibodies were characterized and found to bind a distinct, unusual epitope of the therapeutic. Immunogenicity testing strategies should therefore always include a proper level of antibody characterization, especially when pre-formed antibodies are present. This minimizes false-positives, particularly due to rheumatoid factors, and helps to judge the potential threat in case a genuine pre-dose antibody reactivity is identified.

  9. The Role of Pre-Existing Disturbances in the Effect of Marine Reserves on Coastal Ecosystems: A Modelling Approach

    PubMed Central

    Savina, Marie; Condie, Scott A.; Fulton, Elizabeth A.

    2013-01-01

    We have used an end-to-end ecosystem model to explore responses over 30 years to coastal no-take reserves covering up to 6% of the fifty thousand square kilometres of continental shelf and slope off the coast of New South Wales (Australia). The model is based on the Atlantis framework, which includes a deterministic, spatially resolved three-dimensional biophysical model that tracks nutrient flows through key biological groups, as well as extraction by a range of fisheries. The model results support previous empirical studies in finding clear benefits of reserves to top predators such as sharks and rays throughout the region, while also showing how many of their major prey groups (including commercial species) experienced significant declines. It was found that the net impact of marine reserves was dependent on the pre-existing levels of disturbance (i.e. fishing pressure), and to a lesser extent on the size of the marine reserves. The high fishing scenario resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects on biomass and functional biodiversity. However, under the lower fishing pressure scenario, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives. PMID:23593432

  10. Region-Specific Integration of Embryonic Stem Cell-Derived Neuronal Precursors into a Pre-Existing Neuronal Circuit

    PubMed Central

    Neuser, Franziska; Polack, Martin; Annaheim, Christine; Tucker, Kerry L.; Korte, Martin

    2013-01-01

    Enduring reorganization is accepted as a fundamental process of adult neural plasticity. The most dramatic example of this reorganization is the birth and continuously occurring incorporation of new neurons into the pre-existing network of the adult mammalian hippocampus. Based on this phenomenon we transplanted murine embryonic stem (ES)-cell derived neuronal precursors (ESNPs) into murine organotypic hippocampal slice cultures (OHC) and examined their integration. Using a precise quantitative morphological analysis combined with a detailed electrophysiology, we show a region-specific morphological integration of transplanted ESNPs into different subfields of the hippocampal tissue, resulting in pyramidal neuron-like embryonic stem cell-derived neurons (ESNs) in the Cornu Ammonis (CA1 and CA3) and granule neuron-like ESNs in the dentate gyrus (DG), respectively. Subregion specific structural maturation was accompanied by the development of dendritic spines and the generation of excitatory postsynaptic currents (EPSCs). This cell type specific development does not depend upon NMDA-receptor-dependent synaptic transmission. The presented integration approach was further used to determine the cell-autonomous function of the pan-neurotrophin receptor p75 (P75NTR), as a possible negative regulator of ESN integration. By this means we used p75NTR-deficient ESNPs to study their integration into a WT organotypic environment. We show here that p75NTR is not necessary for integration per se but plays a suppressing role in dendritic development. PMID:23840491

  11. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice.

    PubMed

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-10-20

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the "PICKY" software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients.

  12. Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion.

    PubMed

    Liang, Qiu-Juan; Jiang, Mei; Wang, Xin-Hong; Le, Li-Li; Xiang, Meng; Sun, Ning; Meng, Dan; Chen, Si-Feng

    2015-09-01

    Recurrent stroke is difficult to treat and life threatening. Transfer of anti-inflammatory gene is a potential gene therapy strategy for ischemic stroke. Using recombinant adeno-associated viral vector 1 (rAAV1)-mediated interleukin 10 (IL-10), we investigated whether transfer of beneficial gene into the rat cerebral vessels during interventional treatment for initial stroke could attenuate brain injury caused by recurrent stroke. Male Wistar rats were administered rAAV1-IL-10, rAAV1-YFP, or saline into the left cerebral artery. Three weeks after gene transfer, rats were subjected to occlusion of the left middle cerebral artery (MCAO) for 45 min followed by reperfusion for 24 h. IL-10 levels in serum were significantly elevated 3 weeks after rAAV1-IL-10 injection, and virus in the cerebral vessels was confirmed by in situ hybridization. Pre-existing IL-10 but not YFP decreased the neurological dysfunction scores, brain infarction volume, and the number of injured neuronal cells. AAV1-IL-10 transduction increased heme oxygenase (HO-1) mRNA and protein levels in the infarct boundary zone of the brain. Thus, transduction of the IL-10 gene in the cerebral artery prior to ischemia attenuates brain injury caused by ischemia/reperfusion in rats. This preventive approach for recurrent stroke can be achieved during interventional treatment for initial stroke. © 2015 International Union of Biochemistry and Molecular Biology.

  13. The Concept of Ecthyma Gangrenosum Illustrated by a Fusarium oxysporum Infection in an Immunocompetent Individual.

    PubMed

    Jiang, Yanping; Al-Hatmi, Abdullah M S; Xiang, Yining; Cao, Yu; van den Ende, Albert H G Gerrits; Curfs-Breuker, Ilse; Meis, Jacques F; Lu, Hongguang; de Hoog, G Sybren

    2016-10-01

    Ecthyma gangrenosum (EG) involves necrotic cutaneous lesions caused by bacteria, mainly Pseudomonas aeruginosa, and is usually seen in immunocompromised patients with septicemia. However, clinically similar infections have been published with fungi as etiologic agents. We present a case of an EG-like lesion due to Fusarium oxysporum confirmed by clinical diagnosis, culture and molecular identification and discuss the definition of EG.

  14. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

    PubMed

    Lo, Clement; Jun, Min; Badve, Sunil V; Pilmore, Helen; White, Sarah L; Hawley, Carmel; Cass, Alan; Perkovic, Vlado; Zoungas, Sophia

    2017-02-27

    studies had incompletely reported methodology preventing meta-analysis and leading to low confidence in treatment estimates.Three studies with 241 kidney transplant recipients examined the use of more intensive compared to less intensive insulin therapy in kidney transplant recipients with pre-existing type 1 or 2 diabetes. Evidence for the effects of more intensive compared to less intensive insulin therapy on transplant graft survival, HbA1c, fasting blood glucose, all cause mortality and adverse effects including hypoglycaemia was of very low quality. More intensive versus less intensive insulin therapy resulted in no difference in transplant or graft survival over three to five years in one study while another study showed that more intensive versus less intensive insulin therapy resulted in more rejection events over the three year follow-up (11 events in total; 9 in the more intensive group, P = 0.01). One study showed that more intensive insulin therapy resulted in a lower mean HbA1c (10 ± 0.8% versus 13 ± 0.9%) and lower fasting blood glucose (7.22 ± 0.5 mmol/L versus 13.44 ± 1.22 mmol/L) at 13 months compared with standard insulin therapy. Another study showed no difference between more intensive compared to less intensive insulin therapy on all-cause mortality over a five year follow-up period. All studies showed either an increased frequency of hypoglycaemia or severe hypoglycaemia episodes.Three studies with a total of 115 transplant recipients examined the use of DPP4 inhibitors for new-onset diabetes after transplantation. Evidence for the treatment effect of DPP4 inhibitors on transplant or graft survival, HbA1c and fasting blood glucose levels, all cause mortality, and adverse events including hypoglycaemia was of low quality. One study comparing vildagliptin to placebo and another comparing sitagliptin to placebo showed no difference in transplant or graft survival over two to four months of follow-up. One study comparing vildagliptin to placebo

  15. Pre-existing adversity, level of child protection involvement, and school attendance predict educational outcomes in a longitudinal study.

    PubMed

    Maclean, Miriam J; Taylor, Catherine L; O'Donnell, Melissa

    2016-01-01

    Maltreatment largely occurs in a multiple-risk context. The few large studies adjusting for confounding factors have raised doubts about whether low educational achievement results from maltreatment or co-occurring risk factors. This study examined prevalence, risk and protective factors for low educational achievement among children involved with the child protection system compared to other children. We conducted a population-based record-linkage study of children born in Western Australia who sat national Year 3 reading achievement tests between 2008 and 2010 (N=46,838). The longitudinal study linked data from the Western Australian Department of Education, Department of Child Protection and Family Support, Department of Health, and the Disability Services Commission. Children with histories of child protection involvement (unsubstantiated maltreatment reports, substantiations or out-of-home care placement) were at three-fold increased risk of low reading scores. Adjusting for socio-demographic adversity partially attenuated the increased risk, however risk remained elevated overall and for substantiated (OR=1.68) and unsubstantiated maltreatment (OR=1.55). Risk of low reading scores in the out-of-home care group was fully attenuated after adjusting for socio-demographic adversity (OR=1.16). Attendance was significantly higher in the out-of-home care group and served a protective role. Neglect, sexual abuse, and physical abuse were associated with low reading scores. Pre-existing adversity was also significantly associated with achievement. Results support policies and practices to engage children and families in regular school attendance, and highlight a need for further strategies to prevent maltreatment and disadvantage from restricting children's opportunities for success. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Recrystallization fabrics of sheared quartz veins with a strong pre-existing crystallographic preferred orientation from a seismogenic shear zone

    NASA Astrophysics Data System (ADS)

    Price, Nancy A.; Song, Won Joon; Johnson, Scott E.; Gerbi, Christopher C.; Beane, Rachel J.; West, David P.

    2016-07-01

    Microstructural investigations were carried out on quartz veins in schist, protomylonite, and mylonite samples from an ancient seismogenic strike-slip shear zone (Sandhill Corner shear zone, Norumbega fault system, Maine, USA). We interpret complexities in the microstructural record to show that: (1) pre-existing crystallographic preferred orientations (CPO) in the host rock may persist in the new CPO patterns of the shear zone and (2) the inner and outer parts of the shear zone followed diverging paths of fabric development. The host rocks bounding the shear zone contain asymmetrically-folded quartz veins with a strong CPO. These veins are increasingly deformed and recrystallized with proximity to the shear zone core. Matrix-accommodated rotation and recrystallization may position an inherited c-axis maximum in an orientation coincident with rhomb < a > or basal < a > slip. This inherited CPO likely persists in the shear zone fabric as a higher concentration of poles in one hemisphere of the c-axis pole figure, leading to asymmetric crossed girdle or paired maxima c-axis patterns about the foliation plane. Three observed quartz grain types indicate a general trend of localization with decreasing temperature: (1) large (> 100 μm), low aspect ratio (< 5) and (2) high aspect ratio ( 5-20) grains overprinted by (3) smaller (< 80 μm), low aspect ratio (< 4) grains through subgrain rotation-dominated recrystallization. In the outer shear zone, subgrain rotation recrystallization led to a well-developed c-axis crossed girdle pattern. In the inner shear zone, the larger grains are completely overprinted by smaller grains, but the CPO patterns are relatively poorly developed and are associated with distinctively different misorientation angle histogram profiles ("flat" neighbor-pair profile with similar number fraction for angles from 10 to 90°). This may reflect the preferential activation of grain size sensitive deformation processes in the inner-most part of the

  17. Differentiation of pre-existing trapped methane from thermogenic methane in an igneous-intruded coal by hydrous pyrolysis

    USGS Publications Warehouse

    Dias, Robert F.; Lewan, Michael D.; Birdwell, Justin E.; Kotarba, Maciej J.

    2014-01-01

    So as to better understand how the gas generation potential of coal changes with increasing rank, same-seam samples of bituminous coal from the Illinois Basin that were naturally matured to varying degrees by the intrusion of an igneous dike were subjected to hydrous pyrolysis (HP) conditions of 360 °C for 72 h. The accumulated methane in the reactor headspace was analyzed for δ13C and δ2H, and mol percent composition. Maximum methane production (9.7 mg/g TOC) occurred in the most immature samples (0.5 %Ro), waning to minimal methane values at 2.44 %Ro (0.67 mg/g TOC), and rebounding to 3.6 mg/g TOC methane in the most mature sample (6.76 %Ro). Methane from coal with the highest initial thermal maturity (6.76 %Ro) shows no isotopic dependence on the reactor water and has a microbial δ13C value of −61‰. However, methane from coal of minimal initial thermal maturity (0.5 %Ro) shows hydrogen isotopic dependence on the reaction water and has a δ13C value of −37‰. The gas released from coals under hydrous pyrolysis conditions represents a quantifiable mixture of ancient (270 Ma) methane (likely microbial) that was generated in situ and trapped within the rock during the rapid heating by the dike, and modern (laboratory) thermogenic methane that was generated from the indigenous organic matter due to thermal maturation induced by hydrous pyrolysis conditions. These findings provide an analytical framework for better assessment of natural gas sources and for differentiating generated gas from pre-existing trapped gas in coals of various ranks.

  18. The pressor effect of NO synthase inhibition correlates to pre-existing systolic BP in the rat.

    PubMed

    Elayan, Hamzeh H; Kennedy, Brian P; Ziegler, Michael G

    2002-01-10

    A number of studies have found that the vasopressor effect of nitric oxide (NO) synthase inhibition is small following treatment with hypotensive agents but is enhanced after hypertensive agents, and have implicated NO in the mechanism of action of these drugs. We investigated the hypothesis that the rate of vascular NO synthesis is directly related to blood pressure. The vasopressor effect of 10 mg/kg of L-nitro-L-arginine methyl ester (L-NAME) was studied in relation to changes in BP induced by a variety of treatments in both pentobarbital sodium anesthetized and pithed rats. BP reductions were induced by blood withdrawal, surgery and pithing. BP increases were made by injecting 10 and 15 microg/kg boluses of phenylephrine or by injecting 5% albumin solution. Pithing decreased baseline BP and attenuated the vasopressor effect of L-NAME while phenylephrine increased both BP levels and the hypertensive effect of L-NAME. Volume expansion with 5% albumin solution increased both BP and the vasopressor effect of L-NAME. Both surgery (abdominal incision) and withdrawal of 1 ml blood reduced BP and attenuated the pressor effect of L-NAME. When the results of all these studies were combined, systolic BP was found to correlate strongly with the vasopressor effect of L-NAME (R2 = 0.73, P < 0.0001). Diastolic BP correlated less well with L-NAME (R2 = 0.36, P < 0.0003). The results suggest that shear stress generated by blood flow during the systole releases NO, and lowers BP. The pressor effect of NO synthase inhibition is closely related to pre-existing systolic BP.

  19. Constraints on the Progenitor of SN 2010jl and Pre-existing Hot Dust in its Surrounding Medium

    NASA Astrophysics Data System (ADS)

    Dwek, Eli; Arendt, Richard G.; Fox, Ori D.; Kelly, Patrick L.; Smith, Nathan; Van Dyk, Schuyler D.; Filippenko, Alexei V.; Andrews, Jennifer; Shivvers, Isaac

    2017-10-01

    A search for the progenitor of SN 2010jl, an unusually luminous core-collapse supernova of Type IIn, using pre-explosion Hubble/WFPC2 and Spitzer/IRAC images of the region, yielded upper limits on the UV and near-infrared (IR) fluxes from any candidate star. These upper limits constrain the luminosity and effective temperature of the progenitor, the mass of any pre-existing dust in its surrounding circumstellar medium (CSM), and dust proximity to the star. A lower limit on the CSM dust mass is required to hide a luminous progenitor from detection by Hubble. Upper limits on the CSM dust mass and constraints on its proximity to the star are set by requiring that the absorbed and reradiated IR emission not exceed the IRAC upper limits. Using the combined extinction-IR emission constraints, we present viable {M}{{d}}{--}{R}1 combinations, where M d and R 1 are the CSM dust mass and its inner radius. These depend on the CSM outer radius, dust composition and grain size, and the properties of the progenitor. The results constrain the pre-supernova evolution of the progenitor, and the nature and origin of the observed post-explosion IR emission from SN 2010jl. In particular, an η Car-type progenitor will require at least 4 mag of visual extinction to avoid detection by Hubble. This can be achieved with dust masses ≳ {10}-3 {M}ȯ (less than the estimated 0.2–0.5 {M}ȯ around η Car), which must be located at distances of ≳ {10}16 cm from the star to avoid detection by Spitzer.

  20. Evolution of pre-existing versus acquired resistance to platinum drugs and PARP inhibitors in BRCA-associated cancers.

    PubMed

    Yamamoto, Kimiyo N; Hirota, Kouji; Takeda, Shunichi; Haeno, Hiroshi

    2014-01-01

    Platinum drugs and PARP inhibitors ("PARPis") are considered to be effective in BRCA-associated cancers with impaired DNA repair. These agents cause stalled and collapsed replication forks and create double-strand breaks effectively in the absence of repair mechanisms, resulting in arrest of the cell cycle and induction of cell death. However, recent studies have shown failure of these chemotherapeutic agents due to emerging drug resistance. In this study, we developed a stochastic model of BRCA-associated cancer progression in which there are four cancer populations: those with (i) functional BRCA, (ii) dysfunctional BRCA, (iii) functional BRCA and a growth advantage, and (iv) dysfunctional BRCA and a growth advantage. These four cancer populations expand from one cancer cell with normal repair function until the total cell number reaches a detectable amount. We derived formulas for the probability and expected numbers of each population at the time of detection. Furthermore, we extended the model to consider the tumor dynamics during treatment. Results from the model were validated and showed good agreement with clinical and experimental evidence in BRCA-associated cancers. Based on the model, we investigated conditions in which drug resistance during the treatment course originated from either a pre-existing drug-resistant population or a de novo population, due to secondary mutations. Finally, we found that platinum drugs and PARPis were effective if (i) BRCA inactivation is present, (ii) the cancer was diagnosed early, and (iii) tumor growth is rapid. Our results indicate that different types of cancers have a preferential way of acquiring resistance to platinum drugs and PARPis according to their growth and mutational characteristics.

  1. Programmed death ligand 1 as an indicator of pre-existing adaptive immune responses in human hepatocellular carcinoma.

    PubMed

    Xie, Qian-Kun; Zhao, Yu-Jie; Pan, Tao; Lyu, Ning; Mu, Lu-Wen; Li, Shao-Long; Shi, Mu-De; Zhang, Zhen-Feng; Zhou, Peng-Hui; Zhao, Ming

    2016-07-01

    It is well known that the aberrant expression of programmed death ligand 1 (PD-L1) on tumor cells impairs antitumor immunity. To date, in hepatocellular carcinoma (HCC), the relationship between PD-L1 expression and host-tumor immunity is not well defined. Here, the expression levels of PD-L1 and CD8(+) T cell infiltration were analyzed by immunohistochemistry (IHC) in formalin fixed paraffin embedded (FFPE) specimens from 167 HCC patients undergoing resection. A significant positive association was found between PD-L1 expression and the presence of CD8(+) T cell (p < 0.0001). Moreover, constitutive PD-L1 protein expression was not detected by western blot in HepG2, Hep3B, and 7402 HCC cancer cell lines; but co-cultured these cell lines with INFγ, a cytokine produced by activated CD8(+) T cells, remarkably upregulated PD-L1 expression. In fresh frozen HCC specimens, INFγ was found to be significantly correlated with PD-L1 and CD8(+) gene expression, as evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). These findings indicate that increased PD-L1 level may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity. Both increased intratumoral PD-L1 and CD8(+) were significantly associated with superior DFS (CD8(+): p = 0.03; PD-L1: p = 0.023) and OS (CD8(+): p = 0.001 and PD-L1: p = 0.059), but PD-L1 expression was not independently prognostic. In conclusions, PD-L1 upregulation is mainly induced by activated CD8(+) cytotoxic T cells pre-existing in HCC milieu rather than be constitutively expressed by the tumor cells, and it is a favorable prognostic factor for HCC.

  2. Interactions between propagating rifts and pre-existing linear rheological heterogeneities: insights from 3D analogue experiments of rotational extension

    NASA Astrophysics Data System (ADS)

    Molnar, Nicolas; Cruden, Alexander

    2017-04-01

    Propagating rifts are a natural consequence of lithospheric plates that diverge with respect to each other about a pole of rotation. This process of "unzipping" is common in the geological record, but how rifts interact with pre-existing structures (i.e., with a non-homogeneous lithosphere) as they propagate is poorly understood. Here we report on a series of lithospheric-scale three-dimensional analogue experiments of rotational extension with in-built, variably oriented linear weak zones in the lithospheric mantle, designed to investigate the role that inherited structural or thermal weaknesses play in the localisation of strain and rifting. Surface strain and dynamic topography in the analogue models are quantified by high-resolution particle imaging velocimetry and digital photogrammetry, which allows us to characterise the spatio-temporal evolution of deformation as a function of the orientation of the linear heterogeneities in great detail. The results show that the presence of a linear zone of weakness oriented at low angles with respect to the rift axis (i.e., favourably oriented) produces strain localisation in narrow domains, which enhances the "unzipping" process prior to continental break up. Strong strain partitioning is observed when the linear heterogeneity is oriented at high angles with respect to the rift axis (i.e., unfavourably oriented). In these experiments, early sub-parallel V-shaped basins propagate towards the pole of rotation until they are abandoned and strain is transferred entirely to structures developed in the vicinity of the strongly oblique weak lithosphere zone boundary. The modelling also provides insights on how propagating rift branches that penetrate the weak linear zone boundary are aborted when strain is relayed onto structures that develop in rheologically weaker areas. The experimental results are summarised in terms of their evolution, patterns of strain localisation, and dynamic topography as a function of the

  3. Evaluation of a pre-existing, 3-year household water treatment and handwashing intervention in rural Guatemala.

    PubMed

    Arnold, Benjamin; Arana, Byron; Mäusezahl, Daniel; Hubbard, Alan; Colford, John M

    2009-12-01

    The promotion of household water treatment and handwashing with soap has led to large reductions in child diarrhoea in randomized efficacy trials. Currently, we know little about the health effectiveness of behaviour-based water and hygiene interventions after the conclusion of intervention activities. We present an extension of previously published design (propensity score matching) and analysis (targeted maximum likelihood estimation) methods to evaluate the behavioural and health impacts of a pre-existing but non-randomized intervention (a 3-year, combined household water treatment and handwashing campaign in rural Guatemala). Six months after the intervention, we conducted a cross-sectional cohort study in 30 villages (15 intervention and 15 control) that included 600 households, and 929 children <5 years of age. The study design created a sample of intervention and control villages that were comparable across more than 30 potentially confounding characteristics. The intervention led to modest gains in confirmed water treatment behaviour [risk difference = 0.05, 95% confidence interval (CI) 0.02-0.09]. We found, however, no difference between the intervention and control villages in self-reported handwashing behaviour, spot-check hygiene conditions, or the prevalence of child diarrhoea, clinical acute lower respiratory infections or child growth. To our knowledge this is the first post-intervention follow-up study of a combined household water treatment and handwashing behaviour change intervention, and the first post-intervention follow-up of either intervention type to include child health measurement. The lack of child health impacts is consistent with unsustained behaviour adoption. Our findings highlight the difficulty of implementing behaviour-based household water treatment and handwashing outside of intensive efficacy trials.

  4. Evaluation of a pre-existing, 3-year household water treatment and handwashing intervention in rural Guatemala

    PubMed Central

    Arnold, Benjamin; Arana, Byron; Mäusezahl, Daniel; Hubbard, Alan; Colford, John M

    2009-01-01

    Background The promotion of household water treatment and handwashing with soap has led to large reductions in child diarrhoea in randomized efficacy trials. Currently, we know little about the health effectiveness of behaviour-based water and hygiene interventions after the conclusion of intervention activities. Methods We present an extension of previously published design (propensity score matching) and analysis (targeted maximum likelihood estimation) methods to evaluate the behavioural and health impacts of a pre-existing but non-randomized intervention (a 3-year, combined household water treatment and handwashing campaign in rural Guatemala). Six months after the intervention, we conducted a cross-sectional cohort study in 30 villages (15 intervention and 15 control) that included 600 households, and 929 children <5 years of age. Results The study design created a sample of intervention and control villages that were comparable across more than 30 potentially confounding characteristics. The intervention led to modest gains in confirmed water treatment behaviour [risk difference = 0.05, 95% confidence interval (CI) 0.02–0.09]. We found, however, no difference between the intervention and control villages in self-reported handwashing behaviour, spot-check hygiene conditions, or the prevalence of child diarrhoea, clinical acute lower respiratory infections or child growth. Conclusions To our knowledge this is the first post-intervention follow-up study of a combined household water treatment and handwashing behaviour change intervention, and the first post-intervention follow-up of either intervention type to include child health measurement. The lack of child health impacts is consistent with unsustained behaviour adoption. Our findings highlight the difficulty of implementing behaviour-based household water treatment and handwashing outside of intensive efficacy trials. PMID:19574492

  5. The effect of pre-existing affect on the sexual responses of women with and without a history of childhood sexual abuse.

    PubMed

    Rellini, Alessandra H; Elinson, Samantha; Janssen, Erick; Meston, Cindy M

    2012-04-01

    Women with a history of childhood sexual abuse (CSA) are at greater risk for experiencing sexual problems in their adult lives. Yet, little is known about the possible role of cognitive and affective mechanisms in the development of sexual arousal difficulties in this population. This study investigated the role of pre-existing affect (affect prior to exposure to sexual stimuli) on genital responses, subjective sexual arousal, and affect elicited during the presentation of erotic film excerpts in a community sample of 25 women with and 25 women without a history of CSA. The CSA group showed greater pre-existing negative affect and smaller genital responses to the erotic film stimuli compared to the NSA group. Findings support a moderating effect of CSA, in that pre-existing negative affect was associated with strength of genital responses in the NSA but not in the CSA group. The results did not support a mediation model of pre-existing negative affect as an explanation for smaller physiological sexual responses in the CSA group. Taken together, the findings suggest that pre-existing affect may be more relevant for women with no history of CSA and call for more research on factors implicated in impaired sexual responses in women with a history of CSA.

  6. To which level did the 2010 M 8.8 Maule earthquake fill the pre-existing seismic gap?

    NASA Astrophysics Data System (ADS)

    Wang, Lifeng; Hainzl, Sebastian; Mai, P. Martin

    2017-10-01

    There is a long-standing debate whether or not the 2010 M 8.8 Maule earthquake filled a pre-existing seismic gap in which no large earthquake occurred for about 200 yr. Utilizing the inversion approach of Wang et al. that considers elastic strain accumulation and strain release during the earthquake cycle and includes the fault-coupling state as prior information in coseismic slip modelling, we investigate the inter- and coseismic slip balance for the 2010 M 8.8 Maule earthquake. The coseismic slip model is obtained as the product of three components: the interseismic backslip rate, the strain accumulation time, and the fraction of coseismically released slip potency (the product of slip and slip area) that may either fully or partially release the local strain. We construct slip models using the Slab1.0 fault geometry, and constrain the strain accumulation time for the 2010 Maule earthquake based on historical large earthquakes in the region. The results demonstrate that two slip clusters (north and south of the hypocentre) are required to model the geodetically measured coseismic displacements. The slip patch south of the hypocentre is located in a strongly coupled zone, and possibly released the local strain completely. The slip area north of the hypocentre overlaps with the interseismically creeping zone in which strain buildup may be low. The northern slip patch released higher slip potency than accumulated since the last mega-event in 1751, suggesting a possible dynamic overshoot during coseismic rupture (under the assumption that the last major earthquake has reset the regional strain). Alternatively, the last big event may not have fully released the strain in this region. Our study reveals that the Maule earthquake, combing its coseismic and post-seismic slip over 1.3 yr, released ˜67-72 per cent of the local strain. Remaining strain is concentrated mainly south of the hypocentre, with potency equivalent to an M 8.4 event considering strain accumulation

  7. The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines.

    PubMed

    Idoko, Olubukola T; Okolo, Seline N; Plikaytis, Brian; Akinsola, Adebayo; Viviani, Simonetta; Borrow, Ray; Carlone, George; Findlow, Helen; Elie, Cheryl; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Ota, Martin; Kampmann, Beate

    2014-07-16

    -vaccination titers attained ≥4-fold responses as compared to 76% with high titers where study vaccine was received. Our data confirm the presence of high pre-vaccination Men A antibody concentrations/titers within the African meningitis belt, with significantly higher concentrations in older individuals. Although all participants had significant increase in antibody levels following vaccination, the four-fold or greater response in antibody titers were significantly higher in individuals with lower pre-existing antibody titers, especially after receiving PsA-TT. This finding may have some implications for vaccination strategies adopted in the future.

  8. Transcatheter Heart Valve Selection and Permanent Pacemaker Implantation in Patients With Pre-Existent Right Bundle Branch Block.

    PubMed

    van Gils, Lennart; Tchetche, Didier; Lhermusier, Thibault; Abawi, Masieh; Dumonteil, Nicolas; Rodriguez Olivares, Ramón; Molina-Martin de Nicolas, Javier; Stella, Pieter R; Carrié, Didier; De Jaegere, Peter P; Van Mieghem, Nicolas M

    2017-03-03

    Right bundle branch block is an established predictor for new conduction disturbances and need for a permanent pacemaker (PPM) after transcatheter aortic valve replacement. The aim of the study was to evaluate the absolute rates of transcatheter aortic valve replacement related PPM implantations in patients with pre-existent right bundle branch block and categorize for different transcatheter heart valves. We pooled data on 306 transcatheter aortic valve replacement patients from 4 high-volume centers in Europe and selected those with right bundle branch block at baseline without a previously implanted PPM. Logistic regression was used to evaluate whether PPM rate differed among transcatheter heart valves after adjustment for confounders. Mean age was 83±7 years and 63% were male. Median Society of Thoracic Surgeons score was 6.3 (interquartile range, 4.1-10.2). The following transcatheter valve designs were used: Medtronic CoreValve (n=130; Medtronic, Minneapolis, MN); Edwards Sapien XT (ES-XT; n=124) and Edwards Sapien 3 (ES-3; n=32; Edwards Lifesciences, Irvine, CA); and Boston Scientific Lotus (n=20; Boston Scientific Corporation, Marlborough, MA). Overall permanent pacemaker implantation rate post-transcatheter aortic valve replacement was 41%, and per valve design: 75% with Lotus, 46% with CoreValve, 32% with ES-XT, and 34% with ES-3. The indication for PPM implantation was total atrioventricular block in 98% of the cases. Lotus was associated with a higher PPM rate than all other valves. PPM rate did not differ between ES-XT and ES-3. Ventricular paced rhythm at 30-day and 1-year follow-up was present in 81% at 89%, respectively. Right bundle branch block at baseline is associated with a high incidence of PPM implantation for all transcatheter heart valves. PPM rate was highest for Lotus and lowest for ES-XT and ES-3. Pacemaker dependency remained high during follow-up. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by

  9. Pre-existing normal faults have limited control on the rift geometry of the northern North Sea

    NASA Astrophysics Data System (ADS)

    Claringbould, Johan S.; Bell, Rebecca E.; Jackson, Christopher A.-L.; Gawthorpe, Robert L.; Odinsen, Tore

    2017-10-01

    natural rifts are required to test and refine the predictions of physical and numerical models, more specifically, our study suggests models not explicitly recognising or including thermal or rheological effects might over emphasise the role of discrete pre-existing rift structures such as normal faults.

  10. Effects of Mining-Induced Stress Perturbations on Pre-Existing Faults Near a Deep South African Gold Mine

    NASA Astrophysics Data System (ADS)

    Lucier, A. M.; Heesakkers, V.; Zoback, M. D.; Reches, Z.

    2007-12-01

    For over a century, mining-induced earthquakes have been recorded in the deep underground mining region of Witwatersrand Basin in South Africa. The TauTona gold mine experiences an appreciable number of mining- induced earthquakes and is the site of the Natural Earthquake Laboratory in South African Mines (NELSAM) project. In this work, we constrain the virgin (i.e. unperturbed) state of stress near the TauTona gold mine using an iterative forward modeling approach that combines observations of drilling induced borehole failures in borehole images, boundary element modeling of the mining-induced stress perturbations, and forward modeling of borehole failures based on the results of the boundary element modeling. We find that the state of stress is a normal faulting regime with principal stress orientations that are slightly deviated from vertical and horizontal and therefore denoted with a (*). The maximum principal stress, Sv*, is deviated 0° to 20° from vertical towards the NNW and has a magnitude gradient of 27 ± 0.3 MPa/km. The intermediate principal stress, SHmax*, is inclined 0° to 20° from horizontal with an azimuth of 145° to 168° and has a magnitude gradient of 21.5 to 26 MPa/km. The least principal stress, Shmin*, is inclined 0° to 10° from horizontal with an azimuth of 235° to 258° and has a magnitude gradient of 13 to 15.5 MPa/km. Using this constrained stress state, we investigate the likelihood of faulting to occur both on pre-existing fault planes that are optimally-oriented to the virgin stress state and on faults affected by the mining-perturbed stress field, the latter of which is calculated with boundary element modeling. The far-field stress state indicates that the crust is in a state of frictional faulting equilibrium, such that normal faulting is likely to occur on faults striking SSE and NNW and have a dip angle of approximately 45° to 80°. The mining-induced stress perturbation affects faults relatively closer to the mining

  11. A dairy-based high calcium diet improves glucose homeostasis and reduces steatosis in the context of pre-existing obesity

    USDA-ARS?s Scientific Manuscript database

    High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet-induced obese (DIO) rodents. The influence of Ca and dairy on these phenotypes in the context of pre-existing obesity is not known. Furthermore, interpre...

  12. Effect of the pre-existing carbides on the grain boundary network during grain boundary engineering in a nickel based alloy

    SciTech Connect

    Liu, Tingguang; Xia, Shuang; Li, Hui; Zhou, Bangxin; Bai, Qin

    2014-05-01

    Grain boundary engineering was carried out on an aging-treated nickel based Alloy 690, which has precipitated carbides at grain boundaries. Electron backscatter diffraction technique was used to investigate the grain boundary networks. Results show that, compared with the solution-annealed samples, the aging-treated samples with pre-existing carbides at grain boundaries need longer duration or higher temperature during annealing after low-strain tensile deformation for forming high proportion of low-Σ coincidence site lattice grain boundaries (more than 75%). The reason is that the primary recrystallization is inhibited or retarded owing to that the pre-existing carbides are barriers to grain boundaries migration. - Highlights: • Study of GBE as function of pre-existing GB carbides, tensile strain and annealing • Recrystallization of GBE is inhibited or retarded by the pre-existing carbides. • Retained carbides after annealing show the original GB positions. • More than 80% of special GBs were formed after the modification of GBE processing. • Multiple twinning during recrystallization is the key process of GBE.

  13. Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing

    NASA Astrophysics Data System (ADS)

    Takeda, Haruhiko; Ueda, Yoshihide; Inuzuka, Tadashi; Yamashita, Yukitaka; Osaki, Yukio; Nasu, Akihiro; Umeda, Makoto; Takemura, Ryo; Seno, Hiroshi; Sekine, Akihiro; Marusawa, Hiroyuki

    2017-03-01

    Resistance-associated variant (RAV) is one of the most significant clinical challenges in treating HCV-infected patients with direct-acting antivirals (DAAs). We investigated the viral dynamics in patients receiving DAAs using third-generation sequencing technology. Among 283 patients with genotype-1b HCV receiving daclatasvir + asunaprevir (DCV/ASV), 32 (11.3%) failed to achieve sustained virological response (SVR). Conventional ultra-deep sequencing of HCV genome was performed in 104 patients (32 non-SVR, 72 SVR), and detected representative RAVs in all non-SVR patients at baseline, including Y93H in 28 (87.5%). Long contiguous sequences spanning NS3 to NS5A regions of each viral clone in 12 sera from 6 representative non-SVR patients were determined by third-generation sequencing, and showed the concurrent presence of several synonymous mutations linked to resistance-associated substitutions in a subpopulation of pre-existing RAVs and dominant isolates at treatment failure. Phylogenetic analyses revealed close genetic distances between pre-existing RAVs and dominant RAVs at treatment failure. In addition, multiple drug-resistant mutations developed on pre-existing RAVs after DCV/ASV in all non-SVR cases. In conclusion, multi-drug resistant viral clones at treatment failure certainly originated from a subpopulation of pre-existing RAVs in HCV-infected patients. Those RAVs were selected for and became dominant with the acquisition of multiple resistance-associated substitutions under DAA treatment pressure.

  14. A dairy-based high calcium diet improves glucose homeostasis and reduces further weight gain in high fat fed mice in the context of pre-existing obesity

    USDA-ARS?s Scientific Manuscript database

    Background: High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet-induced obese (DIO) mice. However, the influence of Ca and dairy on these phenotypes in the context of pre-existing obesity is not known. Met...

  15. Lateral propagation of active normal faults throughout pre-existing fault zones: an example from the Southern Apennines, Italy

    NASA Astrophysics Data System (ADS)

    Agosta, Fabrizio; Prosser, Giacomo; Ivo Giano, Salvatore

    2013-04-01

    top, unconformably covered by Miocene clastic deposits. The lower thrust sheet is made up of deep-sea deposits of late Triassic to Eocene age, which include pelagic limestones, radiolarites, marls and turbiditic calcarenites. The relay ramp area is comprised of two main fault sets, which are NW-trending (N120-140E) and NE-trending (N60-70E). Minor E-trending (N90-100E) and NNW-trending (N160-170E) faults are also present. Maximum throws of the most developed faults, which are also characterized by the longest traces, are in the order of 300-400 m. Crosscutting relationships and morphotectonic analyses generally show that the NW-trending faults are the most recent, as also shown by the involvement of Quaternary breccias and near surface fault rocks. Our data indicate that propagation of NW-trending normal faults in the relay ramp area took place thanks to the breaking of a pre-existing structural grain made up, mainly, of NE-trending normal faults. This process determined the different multi-scale properties to the two fault sets, and somehow inhibited the lateral growth of the NW-trending normal faults.

  16. An immunoinhibition approach to overcome the impact of pre-existing antibodies on cut point establishment for immunogenicity assessment of moxetumomab pasudotox.

    PubMed

    Schneider, Amy K; Vainshtein, Inna; Roskos, Lorin K; Chavez, Carlos; Sun, Bo; Liang, Meina

    2016-08-01

    Immunogenicity can impact PK, PD, efficacy and safety of biopharmaceuticals, and is often evaluated as a secondary objective in clinical studies. Methods to detect anti-drug antibodies (ADA) and neutralizing ADA (NAb) are semi-quantitative and utilize cut points to determine positive or negative samples. Assay cut points are established by the statistical analysis of treatment-naïve subject specimens that are assumed ADA and NAb-negative. Pre-existing antibodies to various biopharmaceuticals have been observed in treatment-naïve subjects and may artificially elevate the cut point, resulting in compromised assay sensitivities, inaccuracy in immunogenicity reporting and ultimately misleading assessment of the impact of immunogenicity on clinical outcomes. Although several approaches such as removal of pre-existing antibody samples or increasing the sample dilution could be used for cut point establishment to mitigate impact of pre-existing antibodies, they each have limitations, especially when a high prevalence of pre-existing antibodies is observed. Here we describe an innovative approach used to establish cut points for ADA and NAb assays of moxetumomab pasudotox (moxetumomab), a recombinant anti-CD22 immunotoxin, to which a high prevalence of pre-existing antibodies was observed. In order to overcome the challenges associated with this high prevalence and prevent establishment of an artificially elevated cut point, we developed an immunoinhibition approach that allowed generation of pseudo ADA and NAb-negative populations for cut point determination. Immunoinhibition was performed by adding excess moxetumomab (for ADA) or a non-CD22 binding PE38-containing immunotoxin, CAT-5001 (for NAb), to treatment-naive samples prior to evaluating samples for cut point establishment. This approach successfully eliminated pre-existing antibody activity in treatment-naive samples, enabling establishment of more accurate ADA and NAb assay cut points. A comparative analysis of

  17. Antimicrobial resistance of Staphylococcus pseudintermedius isolates from healthy dogs and dogs affected with pyoderma in Japan.

    PubMed

    Onuma, Kenta; Tanabe, Taishi; Sato, Hisaaki

    2012-02-01

    Staphylococcus pseudintermedius strains were isolated from healthy dogs and dogs with pyoderma in 2000-2002 and 2009. All the isolates from dogs with pyoderma in 1999-2000 and from healthy dogs in 2000-2002 and 2009 were susceptible to cefalexin and/or other cephalosporins and oxacillin. However, 7.1-12.5 and 11.4% of S. pseudintermedius isolates from dogs with pyoderma in 2009 were resistant to cephalosporins and oxacillin, respectively. All S. pseudintermedius isolates from dogs with pyoderma in 1999-2000 and those from healthy dogs in 2000-2002 were susceptible to fluoroquinolones; however, 50% of the S. pseudintermedius strains isolated from dogs with pyoderma in 2009 and 30% of the S. pseudintermedius strains isolated from healthy dogs in 2009 were resistant to fluoroquinolones. Of the 21 oxacillin-resistant S. pseudintermedius (MRSP) isolates, 11 carried SCCmec type V and 10 carried hybrid SCCmec types II-III. Staphylococcus pseudintermedius strains that were resistant to only one of three fluoroquinolones had a mutation in the quinolone resistance determination region of grlA, whereas S. pseudintermedius strains that were resistant to two or more fluoroquinolones had mutations in the quinolone resistance determination regions of both grlA and gyrA.

  18. GAPO syndrome associated with pyoderma vegetans: an unreported co-existence.

    PubMed

    Karadag, A S; Calka, O; Bilgili, S G; Karadag, R; Bulut, G

    2013-01-01

    GAPO syndrome is a rare autosomal recessive disease and an acronym composed of growth retardation, alopecia, pseudoanodontia, optic atrophy. Approximately 38 cases have been reported in literature until now. Pyoderma vegetans is a chronic inflammatory disease characterized with vesicopustular, exudative and vegetative lesions usually localized on face, scalp, axilla and genitalia. Pyoderma vegetans is attributed to a bacterial infection frequently occurring in individuals with an underlying immunosuppressive condition. A 30-year-old female patient was admitted to our clinic with complaint of a hemorrhagic, crusted, exudative vegetative two plaques on the scalp. On her physical examination, she had a prematurely aged face, predominant lower lips, total tooth loss, frontal bossing, enlarged anterior fontanelle, marked scalp veins, micrognatia, depressed nasal bridge, short stature, growth retardation. She was diagnosed as GAPO syndrome as the result of her physical examination. Result of the biopsy taken from scalp was evaluated as pyoderma vegetans. And the diagnosis of pyoderma vegetans was established based on the correlate of both clinical and histopathologic findings. Pyoderma vegetans coexisting with GAPO syndrome has not been reported previously. Thus we wished to report it.

  19. Pyoderma vegetans of the posterior area of the neck: case presentation.

    PubMed

    Meşină, Cristian; Vasile, Ion; Mogoantă, Stelian Ştefăniţă; Ciurea, Marius Eugen; Pârvănescu, Horia; Dumitrescu, Theodor Viorel; Georgescu, Claudia Valentina; Ciobanu, Daniela

    2015-01-01

    Pyoderma vegetans is a rare disease characterized by the presence of vegetant exudative, pustular and erythematous vesiculobullous plaque usually located in the inguinal area and axillary fold. Etiology of pyoderma vegetans is unknown but it is often associated with bacterial infections in immunocompromised patients. Main histopathological characteristics of pyoderma crops are pseudoepitheliomatous hyperplasia and subepidermal, intraepidermal neutrophilic or eosinophilic microabscesses. It is well known that these lesions are commonly associated with colonic inflammatory disease such as ulcerative colitis and Crohn's disease. Not available standard treatment for pyoderma vegetans, although the use of antibiotic therapy was often used with variable results. Standard first-line therapy is the systemic steroids yet. We perform excision of the lesion of the posterior area of the neck with application of the free split-thickness skin graft after 48 hours postoperatively. In this paper, we present a case of pyoderma vegetans with unusual location without associating colonic lesions and a review of literature related to therapeutic and diagnostic problems of this disease.

  20. Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma.

    PubMed

    Summers, Jennifer F; Hendricks, Anke; Brodbelt, David C

    2014-10-08

    Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population. Of 54,600 dogs presented to 73 participating practices in 2010, 683 (1.3%) had a pyoderma diagnosis recorded in available electronic patient record (EPR) data. Antimicrobials were dispensed in 97% of cases and most dogs were prescribed systemic therapy (92%). Agents most frequently prescribed were amoxicillin-clavulanate, cefalexin, clindamycin and cefovecin. Systemic antimicrobials were prescribed for fewer than 14 days in around 40% of study cases reviewed in detail. Prescribed daily doses were below minimum recommended daily dose (MRDD) in 26% of 43 dogs with sufficient information for calculation of minimum dose. Antimicrobial prescribing behaviour for treatment of canine pyoderma was variable but frequently appeared inconsistent with current recommendations. Use of clinical data from primary practice EPRs can provide valuable insight into common clinical conditions and associated prescribing.

  1. Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome

    PubMed Central

    Ram, Renee R.; Margot, Nicolas A.; Barnes, Tiffany L.; White, Kirsten L.; Callebaut, Christian; Miller, Michael D.

    2017-01-01

    T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1.4%; 47 of 3367 integrase sequences); most often among non-B (5.3%) than B (0.9%) HIV-1 subtypes. During INSTI-based therapy, few patients experienced virologic failure with emergent INSTI RAMs (3%; 122 of 3881 patients), among whom T97A emerged infrequently in the presence (n = 6) or absence (n = 8) of primary INSTI RAMs. A comparison between pre-existing and emergent T97A patient populations (i.e., in the absence of primary INSTI RAMs) showed no significant differences in EVG or RAL susceptibility in vitro. Furthermore, among all T97A-containing viruses tested, only 38–44% exhibited reduced susceptibility to EVG and/or RAL (all of low magnitude; <11-fold), while all maintained susceptibility to dolutegravir. Of the patients with pre-existing T97A, 17 had available clinical follow-up: 16 achieved virologic suppression and 1 maintained T97A and INSTI sensitivity without further resistance development. Overall, T97A is an infrequent integrase polymorphism that is enriched among non-B HIV-1 subtypes and can confer low-level reduced susceptibility to EVG and/or RAL. However, detection of T97A does not affect response to INSTI-based therapy with EVG or RAL. These results suggest a very low risk of initiating INSTI-based therapy in patients with pre-existing T97A. PMID:28212411

  2. Pre-Existing Mutations in Reverse Transcriptase of Hepatitis B Virus in Treatment-Naive Chinese Patients with Chronic Hepatitis B

    PubMed Central

    Wang, Jing-Hui; Huang, Ling; Wang, Deng-yu; Zhao, Ling; Zhao, Guo-ping; Wang, Ying

    2015-01-01

    High rate of viral replication and lacking of proofreading activity in hepatitis B virus (HBV) polymerase lead to the generation of mutations in HBV virus. Mutations in the reverse transcriptase (RT) region of HBV polymerase are demonstrated to be strongly associated with drug resistance during antiviral treatment. However, the presence of mutations as well as its clinical significance in treatment-naïve hepatitis patients (defined as pre-existing mutations) need to be further investigated. In the present study, a total of 168 serum samples from treatment-naive chronic hepatitis B (CHB) patients were collected, and the RT region of HBV polymerase was sequenced. The results showed that pre-existing mutations in the RT region of HBV polymerase were detected in 43 of 168 (25.6%) treatment-naive CHB patients within which there were no well-characterized primary nucleotide analogs (NAs) resistance sites. Three dominant sites at rt191, rt207 and rt226 were found mutant in 7(16.28%), 8(18.60%), and 14(32.56%) samples respectively among these 43 patients. No significant correlation was found between pre-existing mutations and gender, age, HBV genotype, ALT, HBeAg or HBV DNA loads. However, patients with pre-existing RT mutations under HBeAg sero-negative status exhibited decreased HBV DNA loads, which contributed to the decreased HBV DNA loads in the total HBeAg sero-negative patients. The above investigation indicated that there was a prevalence of pre-existing mutations in RT region of HBV polymerase which might affect the serum HBV DNA level in treatment-naive CHB patients. Its effects on the occurrence of NAs resistance and the prognosis after treatment need to be further investigated. PMID:25821965

  3. The Role of Pre-Existing Diabetes Mellitus on Hepatocellular Carcinoma Occurrence and Prognosis: A Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Bray, Freddie; Gao, Shan; Gao, Jing; Li, Hong-Lan; Xiang, Yong-Bing

    2011-01-01

    Background The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis. Methods We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models. Results The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients. Conclusion The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes

  4. Quantifying remobilization of pre-existing nitrogen from cuttings to new growth of woody plants using 15N at natural abundance

    PubMed Central

    2013-01-01

    Background For measurements of nitrogen isotope composition at natural abundance, carry-over of pre-existing nitrogen remobilized to new plant growth can cause deviation of measured isotope composition (δ15N) from the δ15Nof newly acquired nitrogen. To account for this problem, a two-step approach was proposed to quantify and correct for remobilized nitrogen from vegetative cuttings of Populus balsamifera L. grown with either nitrate (δ15N = 58.5‰) or ammonium (δ15N = −0.96‰). First, the fraction of carry-over nitrogen remaining in the cutting was estimated by isotope mass balance. Then measured δ15N values were adjusted for the fraction of pre-existing nitrogen remobilized to the plant. Results Mean plant δ15N prior to correction was 49‰ and −5.8‰ under nitrate and ammonium, respectively. Plant δ15N was non-linearly correlated to biomass (r2 = 0.331 and 0.249 for nitrate and ammonium, respectively; P < 0.05) where the δ15N of plants with low biomass approached the δ15N of the pre-existing nitrogen. Approximately 50% of cutting nitrogen was not remobilized, irrespective of size. The proportion of carry-over nitrogen in new growth was not different between sources but ranged from less than 1% to 21% and was dependent on plant biomass and, to a lesser degree, the size of the cutting. The δ15N of newly acquired nitrogen averaged 52.7‰ and −6.4‰ for nitrate and ammonium-grown plants, respectively; both lower than their source values, as expected. Since there was a greater difference in δ15N between the carried-over pre-existing and newly assimilated nitrogen where nitrate was the source, the difference between measured δ15N and adjusted δ15N was also greater. There was no significant relationship between biomass and plant δ15N with either ammonium or nitrate after adjusting for carry-over nitrogen. Conclusion Here, we provide evidence of remobilized pre-existing nitrogen influencing δ15N of new growth of P. balsamifera L

  5. Quantifying remobilization of pre-existing nitrogen from cuttings to new growth of woody plants using 15N at natural abundance.

    PubMed

    Kalcsits, Lee A; Guy, Robert D

    2013-07-12

    For measurements of nitrogen isotope composition at natural abundance, carry-over of pre-existing nitrogen remobilized to new plant growth can cause deviation of measured isotope composition (δ15N) from the δ15Nof newly acquired nitrogen. To account for this problem, a two-step approach was proposed to quantify and correct for remobilized nitrogen from vegetative cuttings of Populus balsamifera L. grown with either nitrate (δ15N = 58.5‰) or ammonium (δ15N = -0.96‰). First, the fraction of carry-over nitrogen remaining in the cutting was estimated by isotope mass balance. Then measured δ15N values were adjusted for the fraction of pre-existing nitrogen remobilized to the plant. Mean plant δ15N prior to correction was 49‰ and -5.8‰ under nitrate and ammonium, respectively. Plant δ15N was non-linearly correlated to biomass (r2 = 0.331 and 0.249 for nitrate and ammonium, respectively; P < 0.05) where the δ15N of plants with low biomass approached the δ15N of the pre-existing nitrogen. Approximately 50% of cutting nitrogen was not remobilized, irrespective of size. The proportion of carry-over nitrogen in new growth was not different between sources but ranged from less than 1% to 21% and was dependent on plant biomass and, to a lesser degree, the size of the cutting. The δ15N of newly acquired nitrogen averaged 52.7‰ and -6.4‰ for nitrate and ammonium-grown plants, respectively; both lower than their source values, as expected. Since there was a greater difference in δ15N between the carried-over pre-existing and newly assimilated nitrogen where nitrate was the source, the difference between measured δ15N and adjusted δ15N was also greater. There was no significant relationship between biomass and plant δ15N with either ammonium or nitrate after adjusting for carry-over nitrogen. Here, we provide evidence of remobilized pre-existing nitrogen influencing δ15N of new growth of P. balsamifera L. A simple, though approximate

  6. Efficacy of tylosin tablets for the treatment of pyoderma due to Staphylococcus intermedius infection in dogs.

    PubMed Central

    Scott, D W; Miller, W H; Cayatte, S M; Bagladi, M S

    1994-01-01

    Tylosin tablets (20 mg/kg, q12h) were administered orally to 21 dogs with superficial or deep staphylococcal pyodermas. Response to therapy was excellent in 90.5% of the dogs, and in vitro susceptibility testing correlated perfectly with therapeutic response. Duration of therapy varied from 17 to 91 days, with an average of 33 days. Relapses occurred in 28.6% of the dogs within a three-month period. No side effects were reported. Under the conditions of the study, tylosin was an effective and safe antibiotic for the treatment of staphylococcal pyoderma in dogs. PMID:7994702

  7. Heterogeneity of blastomycosis-like pyoderma: A selection of cases from the last 35 years.

    PubMed

    Scuderi, Salvatore; O'Brien, Blake; Robertson, Ivan; Weedon, David

    2017-05-01

    Blastomycosis-like pyoderma is a form of pyoderma with variable clinical findings and histopathological features. We present a case series of 39 patients collected over a 35-year period to demonstrate its clinical features and histological findings. The most common clinical presentations found were solitary plaques, solitary nodules, sinuses, crypts, verrucous plaques and discharge, usually on sun-exposed skin. The most common histopathological findings were chronic granulomatous inflammation, suppurative inflammation, sinus and abscess formation, pseudoepitheliomatous hyperplasia, transepidermal elimination and scarring. We discuss its treatment and the recent literature that has focused on its response to acitretin. © 2016 The Australasian College of Dermatologists.

  8. Blastomycosis-like pyoderma in association with recurrent vesicular hand eczema: good response to acitretin.

    PubMed

    Cecchi, Roberto; Bartoli, Laura; Brunetti, Luigi; Pavesi, Mario

    2011-03-15

    Blastomycosis-like pyoderma, also known as pyoderma vegetans, is an uncommon disease characterized by vegetating skin lesions mimicking blastomycosis or warty tuberculosis, often associated with staphylococcal and streptococcal infections. It is more commonly observed in elderly patients with impaired immunological capacity, and is often unresponsive to various therapeutic modalities. We describe a case of BLP that occurred on the palmar aspect of the left hand in an elderly female, affected with recurrent vesicular hand eczema. The disease resolved completely following the administration of oral acitretin 25 mg/day for 10 weeks.

  9. The length of pre-existing fissures effects on the mechanical properties of cracked red sandstone and strength design in engineering.

    PubMed

    Wu, Jiangyu; Feng, Meimei; Yu, Bangyong; Han, Guansheng

    2017-08-30

    It is important to study the mechanical properties of cracked rock to understand the engineering behavior of cracked rock mass. Consequently, the influence of the length of pre-existing fissures on the strength, deformation, acoustic emission (AE) and failure characteristics of cracked rock specimen was analyzed, and the optimal selection of strength parameter in engineering design was discussed. The results show that the strength parameters (stress of dilatancy onset and uniaxial compressive strength) and deformation parameters (axial strain and circumferential strain at dilatancy onset and peak point) of cracked rock specimen decrease with the increase of the number of pre-existing fissures, and the relations which can use the negative exponential function to fit. Compared with the intact rock specimens, the different degrees of stress drop phenomena were produced in the process of cracked rock specimens when the stress exceeds the dilatancy onset. At this moment, the cracked rock specimens with the existence of stress drop are not instantaneous failure, but the circumferential strain, volumetric strain and AE signals increase burstingly. And the yield platform was presented in the cracked rock specimen with the length of pre-existing fissure more than 23mm, the yield failure was gradually conducted around the inner tip of pre-existing fissure, the development of original fissures and new cracks was evolved fully in rock. However, the time of dilatancy onset is always ahead of the the time of that point with the existence of stress drop. It indicates that the stress of dilatancy onset can be as the parameter of strength design in rock engineering, which can effectively prevent the large deformation of rock. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing

    PubMed Central

    Takeda, Haruhiko; Ueda, Yoshihide; Inuzuka, Tadashi; Yamashita, Yukitaka; Osaki, Yukio; Nasu, Akihiro; Umeda, Makoto; Takemura, Ryo; Seno, Hiroshi; Sekine, Akihiro; Marusawa, Hiroyuki

    2017-01-01

    Resistance-associated variant (RAV) is one of the most significant clinical challenges in treating HCV-infected patients with direct-acting antivirals (DAAs). We investigated the viral dynamics in patients receiving DAAs using third-generation sequencing technology. Among 283 patients with genotype-1b HCV receiving daclatasvir + asunaprevir (DCV/ASV), 32 (11.3%) failed to achieve sustained virological response (SVR). Conventional ultra-deep sequencing of HCV genome was performed in 104 patients (32 non-SVR, 72 SVR), and detected representative RAVs in all non-SVR patients at baseline, including Y93H in 28 (87.5%). Long contiguous sequences spanning NS3 to NS5A regions of each viral clone in 12 sera from 6 representative non-SVR patients were determined by third-generation sequencing, and showed the concurrent presence of several synonymous mutations linked to resistance-associated substitutions in a subpopulation of pre-existing RAVs and dominant isolates at treatment failure. Phylogenetic analyses revealed close genetic distances between pre-existing RAVs and dominant RAVs at treatment failure. In addition, multiple drug-resistant mutations developed on pre-existing RAVs after DCV/ASV in all non-SVR cases. In conclusion, multi-drug resistant viral clones at treatment failure certainly originated from a subpopulation of pre-existing RAVs in HCV-infected patients. Those RAVs were selected for and became dominant with the acquisition of multiple resistance-associated substitutions under DAA treatment pressure. PMID:28361915

  11. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion.

    PubMed

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth.

  12. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion

    PubMed Central

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth. PMID:26934465

  13. Temperature-Dependent Structural Changes of Parkinson's Alpha-Synuclein Reveal the Role of Pre-Existing Oligomers in Alpha-Synuclein Fibrillization

    PubMed Central

    Ariesandi, Winny; Chang, Chi-Fon; Chen, Tseng-Erh; Chen, Yun-Ru

    2013-01-01

    Amyloid fibrils of α-synuclein are the main constituent of Lewy bodies deposited in substantial nigra of Parkinson's disease brains. α-Synuclein is an intrinsically disordered protein lacking compact secondary and tertiary structures. To enhance the understanding of its structure and function relationship, we utilized temperature treatment to study α-synuclein conformational changes and the subsequent effects. We found that after 1 hr of high temperature pretreatment, >80°C, α-synuclein fibrillization was significantly inhibited. However, the temperature melting coupled with circular dichroism spectra showed that α-synuclein was fully reversible and the NMR studies showed no observable structural changes of α-synuclein after 95°C treatment. By using cross-linking and analytical ultracentrifugation, rare amount of pre-existing α-synuclein oligomers were found to decrease after the high temperature treatment. In addition, a small portion of C-terminal truncation of α-synuclein also occurred. The reduction of pre-existing oligomers of α-synuclein may contribute to less seeding effect that retards the kinetics of amyloid fibrillization. Overall, our results showed that the pre-existing oligomeric species is a key factor contributing to α-synuclein fibrillization. Our results facilitate the understanding of α-synuclein fibrillization. PMID:23349712

  14. Pre-existing disease: the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial.

    PubMed

    Orwelius, Lotti; Nordlund, Anders; Nordlund, Peter; Simonsson, Eva; Bäckman, Carl; Samuelsson, Anders; Sjöberg, Folke

    2010-01-01

    The aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life. Prospective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age >or= 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for. Only small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible. A large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the effect of pre-existing disease is further

  15. Pre-existing disease: the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial

    PubMed Central

    2010-01-01

    Introduction The aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life. Methods Prospective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age ≥ 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for. Results Only small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible. Conclusions A large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the

  16. Burden of paediatric pyoderma and scabies in North West Queensland.

    PubMed

    Whitehall, John; Kuzulugil, Deniz; Sheldrick, Kyle; Wood, Angela

    2013-02-01

    The study aims to assess the health burden of children admitted with 'scabies' to Mt Isa Hospital, the referral centre for North West Queensland, from 2006 to 2010. This is a retrospective chart audit of admissions of children with 'scabies' including age, sex, date, residence, Indigenous status, result of skin swabs and length of stay, and the number of admissions with acute rheumatic fever (ARF) and acute post-streptococcal glomerulo-nephritis (APSGN) in that period. Financial burden was estimated from daily bed costs and transportation. There were 113 admissions with mean age of 23/12: 11% were <2/12 and mean stay was 4.5 days. 19 were admitted twice, 5 thrice and 2 four times. 7 individuals accounted for 25% of admissions. 'Scabies' accounted for 10.1% of medical admissions <5 years of age. Admissions increased from 10 in 2005 to 39 in 2010. The minimum cost per admission was $9584.07. Seventy-one per cent of swabs grew Group A streptococcus, all sensitive to penicillin. Sixty-three per cent of these were accompanied by Staphylococcus aureus, which was the sole organism in 18%. Sixty-four per cent of S. aureus were methicillin resistant. There were 29 admissions for ARF and 23 with APSGN. All children with 'scabies' and ARF and all but three with APSGN were Indigenous. Pyoderma and scabies are major health burdens in North West Queensland, requiring organised community-based prevention. The number of repeat admissions emphasises the futility of individual treatment. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  17. A case of methicillin-resistant Staphylococcus pseudintermedius (MRSP) pyoderma in a Labrador retriever dog.

    PubMed

    Wan, Jennifer

    2014-11-01

    An 8-year-old, neutered male Labrador retriever dog with generalized pruritis had a history of recurring atopic dermatitis and superficial pyoderma. Cocci and yeast were found on cytology and methicillin-resistant Staphylococcus pseudintermedius was cultured. A regimen of marbofloxacin, dexamethasone, ketoconazole, and cyclosporine in addition to bathing with 2% chlorhexidine shampoo resulted in marked improvement.

  18. Efficacy of a surgical scrub including 2% chlorhexidine acetate for canine superficial pyoderma.

    PubMed

    Murayama, Nobuo; Nagata, Masahiko; Terada, Yuri; Shibata, Sanae; Fukata, Tsuneo

    2010-12-01

    The clinical efficacy of a surgical scrub containing 2% chlorhexidine acetate (2CA; Nolvasan® Surgical Scrub; Fort Dodge Animal Health, USA) was evaluated for the topical management of canine superficial pyoderma. The first study was a randomized, double-blind, controlled trial. The control was a shampoo containing 4% chlorhexidine gluconate (4CG; Skin Clinic Shampoo; CHD MEDICS, Goyang, Korea). Ten dogs with symmetrical lesions of canine superficial pyoderma were allocated to receive either 2CA or the control shampoo applied to either side of the body twice weekly for 1 week. Both the owners and the investigators subjectively scored skin lesions including pruritus, erythema, crusted papules and scales on a scale of 0-3. The 2CA and 4CG resulted in almost the same degree of improvement of skin lesions, and there were no significant differences between the two groups. The second study was an open trial of 2CA monotherapy in eight dogs with cefalexin-resistant Staphylococcus intermedius group-associated superficial pyoderma. The 2CA monotherapy was applied every 2 days for 2 weeks. Five dogs improved with 2CA monotherapy, one partially improved and two did not. No adverse reactions were seen in either trial. This suggests that a 2CA surgical scrub could be a useful and safe topical adjunct therapy for dogs with superficial pyoderma involving cefalexin-resistant Staphylococcus intermedius group.

  19. A case of methicillin-resistant Staphylococcus pseudintermedius (MRSP) pyoderma in a Labrador retriever dog

    PubMed Central

    Wan, Jennifer

    2014-01-01

    An 8-year-old, neutered male Labrador retriever dog with generalized pruritis had a history of recurring atopic dermatitis and superficial pyoderma. Cocci and yeast were found on cytology and methicillin-resistant Staphylococcus pseudintermedius was cultured. A regimen of marbofloxacin, dexamethasone, ketoconazole, and cyclosporine in addition to bathing with 2% chlorhexidine shampoo resulted in marked improvement. PMID:25392557

  20. The effects of pre-existing discontinuities on the surface expression of normal faults: Insights from wet-clay analog modeling

    NASA Astrophysics Data System (ADS)

    Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Burrato, Pierfrancesco; Seno, Silvio; Valensise, Gianluca

    2016-08-01

    We use wet-clay analog models to investigate how pre-existing discontinuities (i.e. structures inherited from previous tectonic phases) affect the evolution of a normal fault at the Earth's surface. To this end we first perform a series of three reference experiments driven by a 45° dipping master fault unaffected by pre-existing discontinuities to generate a mechanically isotropic learning set of models. We then replicate the experiment six times introducing a 60°-dipping precut in the clay cake, each time with a different attitude and orientation with respect to an initially-blind, 45°-dipping, master normal fault. In all experiments the precut intersects the vertical projection of the master fault halfway between the center and the right-hand lateral tip. All other conditions are identical for all seven models. By comparing the results obtained from the mechanically isotropic experiments with results from experiments with precuts we find that the surface evolution of the normal fault varies depending on the precut orientation. In most cases the parameters of newly-forming faults are strongly influenced. The largest influence is exerted by synthetic and antithetic discontinuities trending respectively at 30° and 45° from the strike of the master fault, whereas a synthetic discontinuity at 60° and an antithetic discontinuity at 30° show moderate influence. Little influence is exerted by a synthetic discontinuity at 45° and an antithetic discontinuity at 60° from the strike of the master fault. We provide a ranking chart to assess fault-to-discontinuity interactions with respect to essential surface fault descriptors, such as segmentation, vertical-displacement profile, maximum displacement, and length, often used as proxies to infer fault properties at depth. Considering a single descriptor, the amount of deviation induced by different precuts varies from case to case in a rather unpredictable fashion. Multiple observables should be taken into

  1. Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre-existing chronic kidney disease.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Hashimoto, Yasunobu; Yoshida, Kazuhiko; Tanabe, Kazunari

    2014-06-01

    We compared kidney functional recovery between patients with pre-existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre-existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: -6.8%, group 2: -18%, group 3: -7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: -0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre-existing chronic kidney

  2. Investigating the Influence of Pre-Existing Basement Structures on the Propagation of the Malawi Rift using SRTM, RADARSAT, and Aeromagnetic Data

    NASA Astrophysics Data System (ADS)

    Robertson, K.; Atekwana, E. A.; Abdelsalam, M. G.; Laó-Dávila, D. A.

    2015-12-01

    The Malawi rift is a Neogene, amagmatic rift located where the Western Branch of the East Africa Rift System (EARS) terminates. In more mature rifts, magmatism is frequently recognized as a driving factor in rift propagation; however, the amagmatic nature of the Malawi rift permits investigation into the relationship between pre-existing structures and current rift propagation, without the influence of magmatism. To map surface structures, we used Shuttle Radar Topography Mission (SRTM) Digital Elevation Model (DEM) and RADARSAT imagery over southern Malawi. To process the SRTM data, we applied edge enhancing filters and derivatives, and extracted topographic profiles to examine scarp height and minimum vertical exposed displacement. We mapped morphologically-defined structures by filtering the RADARSAT imagery using an enhanced lee filter to reduce noise and a Laplacian filter for edge enhancement. To examine Precambrian basement structures, we filtered aeromagnetic data using vertical and horizontal derivatives, tilt derivative, and analytic signal to create magnetic anomaly maps. Surface mapping indicated three primary trends in the southern Malawi rift: NW-SE (dominant), NE-SW, both of which are most likely the remnants of Mesozoic Karoo rifting, and a NNE-SSW trend seen in Neogene rifting. The Precambrian basement structural mapping also reveals three primary trends: WNW-ESE, NE-SW, and NW-SE. Ductile deformation causes the dominant basement fabric to change, switching polarity as the rift propagated southward from NE-SW orientation to NW-SE and WNW-ESE orientations, and back to a NE-SW orientation. In general, the surficial structures follow this trend. In some areas, however, the more recent rifting cut across pre-existing basement structures, possibly due to rheological heterogeneities or selective strain partitioning. Nonetheless, pre-existing basement structures played a critical role in strain localization and fault propagation in Malawi. However

  3. Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity.

    PubMed

    Kuether, E L; Schroeder, J A; Fahs, S A; Cooley, B C; Chen, Y; Montgomery, R R; Wilcox, D A; Shi, Q

    2012-08-01

    The development of inhibitory antibodies, referred to as inhibitors, against exogenous factor VIII in a significant subset of patients with hemophilia A remains a persistent challenge to the efficacy of protein replacement therapy. Our previous studies using the transgenic approach provided proof-of-principle that platelet-specific expression could be successful in treating hemophilia A in the presence of inhibitory antibodies. To investigate a clinically translatable approach for platelet gene therapy of hemophilia A with pre-existing inhibitors. Platelet FVIII expression in preimmunized FVIII(null) mice was introduced by transplantation of lentivirus-transduced bone marrow or enriched hematopoietic stem cells. FVIII expression was determined with a chromogenic assay. The transgene copy number per cell was quantitated with real-time PCR. Inhibitor titer was measured with the Bethesda assay. Phenotypic correction was assessed by the tail clipping assay and an electrolytically induced venous injury model. Integration sites were analyzed with linear amplification-mediated PCR. Therapeutic levels of platelet FVIII expression were sustained in the long term without evoking an anti-FVIII memory response in the transduced preimmunized recipients. The tail clip survival test and the electrolytic injury model confirmed that hemostasis was improved in the treated animals. Sequential bone marrow transplants showed sustained platelet FVIII expression resulting in phenotypic correction in preimmunized secondary and tertiary recipients. Lentivirus-mediated platelet-specific gene transfer improves hemostasis in mice with hemophilia A with pre-existing inhibitors, indicating that this approach may be a promising strategy for gene therapy of hemophilia A even in the high-risk setting of pre-existing inhibitory antibodies. © 2012 International Society on Thrombosis and Haemostasis.

  4. High Frequency of Pre-Existing Type 2 Diabetes in a Series of Pregnant Women Referred for "Gestational Diabetes" in a Large Canadian Indigenous Community.

    PubMed

    Toth, Ellen L; Keith, Kristin-Lee; Littlechild, Randy; Myskiw, Joy; Meneen, Kari; Buckreus, Kelli; Oster, Richard T

    2016-12-01

    We examined the referral processes and true diagnostic classifications for diabetes complicating pregnancy in a series of 62 pregnant women consecutively referred to a diabetes education and treatment centre in a large Indigenous community in Alberta, Canada. The referrals were made over a 5-year period (2010 to 2015). The main findings of this analysis were the high frequency (38.7%) of pre-existing type 2 diabetes and previously undiagnosed or unrecognized overt diabetes and the deficiencies in early testing and recognition.

  5. Mother/daughter relationships during pregnancy and the transition to motherhood of women with pre-existing diabetes: raising some issues.

    PubMed

    Stenhouse, Elizabeth; Letherby, Gayle

    2011-04-01

    In pregnancies complicated by pre-existing diabetes, there is a higher incidence of adverse pregnancy outcome. Several reports including the Confidential Enquiry into Maternal and Child Health, Diabetes in Pregnancy--are we providing the best care? (2007) highlighted the need for family involvement before/during pregnancy and in early motherhood with the aim of making pregnancy and the transition to motherhood a positive and fulfilling experience. Exploring the midwifery, sociological and diabetes literature may assist in gaining a better understanding of the complexities surrounding conception, pregnancy, childbirth and motherhood within the context of diabetes. Copyright © 2009 Elsevier Ltd. All rights reserved.

  6. Assessing the reactivation potential of pre-existing fractures in the southern Karoo, South Africa: Evaluating the potential for sustainable exploration across its Critical Zone

    NASA Astrophysics Data System (ADS)

    Dhansay, Taufeeq; Navabpour, Payman; de Wit, Maarten; Ustaszewski, Kamil

    2017-10-01

    Understanding the kinematics of pre-existing fractures under the present-day stress field is an indispensable prerequisite for hydraulically increasing fracture-induced rock permeability, i.e. through hydraulic stimulation, which forms the basis of economically viable exploitation of resources such as natural gas and geothermal energy. Predicting the likelihood of reactivating pre-existing fractures in a target reservoir at particular fluid injection pressures requires detailed knowledge of the orientations and magnitudes of the prevailing stresses as well as pore fluid pressures. In the absence of actual in-situ stress measurements, e.g. derived from boreholes, as is mostly the case in previously underexplored "frontier areas", such predictions are often difficult. In this study, the potential of reactivating pre-existing fractures in a likely exploration region of the southern Karoo of South Africa is investigated. The orientations of the present-day in-situ stresses were assessed from surrounding earthquake focal mechanisms, implying c. NW-SE oriented maximum horizontal stress and a stress regime changing between strike-slip and normal faulting. A comparison with paleo-stress axes derived from inverted fault-slip data suggests that the stress field very likely did not experience any significant reorientation since Cretaceous times. Maximum possible in-situ stress magnitudes are estimated by assuming that these are limited by frictional strength on pre-existing planes and subsequently, slip and dilation tendency calculations were performed, assuming hydrostatic pore fluid pressures of c. 32 MPa at targeted reservoir depth. The results suggest that prevalent E-W and NW-SE oriented sub-vertical fractures are likely to be reactivated at wellhead pressures exceeding hydrostatic pore fluid pressures by as little as 2-5 MPa, while less prevalent sub-horizontal and moderately inclined fractures require higher wellhead pressures that are still technically feasible

  7. Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue.

    PubMed

    Lappas, Martha

    2014-02-01

    To determine the effect of maternal obesity, gestational diabetes mellitus (GDM) and adipokines on the expression of genes involved in fatty acid uptake, transport, synthesis and metabolism. Human subcutaneous and omental adipose tissues were obtained from lean, overweight and obese normal glucose tolerant (NGT) women and women with GDM. Quantitative RT-PCR (qRT-PCR) was performed to determine the level of expression. Adipose tissue explants were performed to determine the effect of the adipokines TNFα, IL-1β and leptin on adipose tissue gene expression. Pre-existing maternal obesity and GDM are associated with decreased expression in genes involved in fatty acid uptake and intracellular transport (LPL, FATP2, FATP6, FABPpm and ASCL1), triacylglyceride (TAG) biosynthesis (MGAT1,7 MGAT2 and DGAT1), lipogenesis (FASN) and lipolysis (PNPLA2, HSL and MGLL). Decreased gene expression was also observed for the transcription factors involved in lipid metabolism (LXRα, PPARα, PPARδ, PPARγ, RXRα and SREBP1c). On the other hand, the gene expression of the adipokines TNFα, IL-1β and or leptin was increased in adipose tissue from obese and GDM women. Functional in vitro studies revealed that these adipokines decreased the gene expression of LPL, FATP2, FATP6, ASCL1, PNPLA2, PPARδ, PPARγ and RXRα. Pregnancies complicated by pre-existing maternal obesity and GDM are associated with abnormal adipose tissue lipid metabolism, which may play a role in the pathogenesis of these diseases. © 2014.

  8. Increased CD8+ T cell memory to concurrent infection at the expense of increased erosion of pre-existing memory: the paradoxical role of IL-15.

    PubMed

    Chapdelaine, Yvan; Smith, Dean K; Pedras-Vasconcelos, Joao A; Krishnan, Lakshmi; Sad, Subash

    2003-11-15

    The use of cytokines during vaccination, particularly IL-15, is being considered due to the unique ability of IL-15 to enhance the proliferation of memory CD8(+) T cells. However, as homeostatic mechanisms limit excessive lymphocyte expansion, we addressed the consequences of this enhancement of T cell memory by IL-15. Infection of mice with either recombinant Mycobacterium bovis (BCG) expressing IL-15 (BCG-IL-15) or BCG and purified IL-15 resulted in an increased CD44, IL-2Rbeta expression and increased frequency of IFN-gamma-secreting CD8(+) T cells. Surprisingly, the enhancement of memory to concurrent infection by IL-15 exacerbated the attrition of pre-existing memory. Infection of mice with Listeria monocytogenes expressing OVA resulted in potent OVA(257-264)-specific CD8(+) T cell memory, and a challenge of these mice with either BCG-IL-15 or BCG and purified IL-15 resulted in an increased erosion of OVA(257-264)-specific CD8(+) T cell memory, relative to BCG. Enhancement in the erosion of OVA-specific CD8(+) T cell memory by BCG-IL-15 resulted in a consequently greater impairment in protection against a challenge with OVA-expressing tumor cells. We thus raise important questions regarding vaccinations that are aimed at maximizing T cell memory without considering the impact on pre-existing T cell memory.

  9. Reduction in Noise-Induced Functional Loss of the Cochleae in Mice with Pre-Existing Cochlear Dysfunction Due to Genetic Interference of Prestin

    PubMed Central

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation. PMID:25486270

  10. Lack of efficacy of pre bronchoscopy inhaled salbutamol on symptoms and lung functions in patients with pre-existing airway obstruction

    PubMed Central

    Mohan, Anant; Momin, Indrajit; Poulose, Rosemary; Mohan, Charu; Madan, Karan; Hadda, Vijay; Guleria, Randeep; Pandey, RM

    2016-01-01

    Background: Fiberoptic bronchoscopy (FOB) may exaggerate symptoms and lung functions in patients with pre-existing airway obstruction. Interventions which can alleviate or minimize this procedure-related bronchospasm, especially in this high-risk group are, therefore, required. Methods: A double-blinded randomized controlled trial was conducted to evaluate the efficacy of 400 μg of inhaled salbutamol on patients with spirometric evidence of airflow obstruction planned for FOB. Patient's dyspnea, procedure tolerability, and change in spirometry were assessed before and after the procedure. Results: A total of 50 patients were enrolled (78% males), with a mean (standard deviation) age of 49.8 (6.2) years. There was a significant fall in % predicted FEV1 within each group compared to their respective pre-bronchoscopy values. However, no significant difference in the % predicted or absolute FEV1 level was observed between the two groups. Similarly, although both groups experienced increased dyspnea immediately following FOB, this difference was not significant between the two groups either on the Borg or visual analog scale scales. Pre-FOB anxiety levels and the tolerability of the procedure as assessed by the bronchoscopist were similar in both groups. Conclusion: FOB in patients with pre-existing airway obstruction aggravates cough and dyspnea, with a concomitant decline in FEV1 and FVC. The administration of pre-FOB inhaled salbutamol does not have any significant beneficial effect on procedure-related outcomes. PMID:27578926

  11. Pre-existing oblique transfer zones and transfer/transform relationships in continental margins: New insights from the southeastern Gulf of Aden, Socotra Island, Yemen

    NASA Astrophysics Data System (ADS)

    Bellahsen, N.; Leroy, S.; Autin, J.; Razin, P.; d'Acremont, E.; Sloan, H.; Pik, R.; Ahmed, A.; Khanbari, K.

    2013-11-01

    Transfer zones are ubiquitous features in continental rifts and margins, as are transform faults in oceanic lithosphere. Here, we present a structural study of the Hadibo Transfer Zone (HTZ), located in Socotra Island (Yemen) in the southeastern Gulf of Aden. There, we interpret this continental transfer fault zone to represent a reactivated pre-existing structure. Its trend is oblique to the direction of divergence and it has been active from the early up to the latest stages of rifting. One of the main oceanic fracture zones (FZ), the Hadibo-Sharbithat FZ, is aligned with and appears to be an extension of the HTZ and is probably genetically linked to it. Comparing this setting with observations from other Afro-Arabian rifts as well as with passive margins worldwide, it appears that many continental transfer zones are reactivated pre-existing structures, oblique to divergence. We therefore establish a classification system for oceanic FZ based upon their relationship with syn-rift structures. Type 1 FZ form at syn-rift structures and are late syn-rift to early syn-OCT. Type 2 FZ form during the OCT formation and Type 3 FZ form within the oceanic domain, after the oceanic spreading onset. The latter are controlled by far-field forces, magmatic processes, spreading rates, and oceanic crust rheology.

  12. Cladodes, leaf-like organs in Asparagus, show the significance of co-option of pre-existing genetic regulatory circuit for morphological diversity of plants.

    PubMed

    Nakayama, Hokuto; Yamaguchi, Takahiro; Tsukaya, Hirokazu

    2012-08-01

    Plants in the genus Asparagus have determinate leaf-like organs called cladodes in the position of leaf axils. Because of their leaf-like morphology, axillary position, and morphological variation, it has been unclear how this unusual organ has evolved and diversified. In the previous study, we have shown that cladodes in the genus Asparagus are modified axillary shoots and proposed a model that cladodes have arisen by co-option and deployment of genetic regulatory circuit (GRC) involved in leaf development. Moreover, we proposed that the alteration of the expression pattern of genes involved in establishment of adaxial/abaxial polarity has led to the morphological diversification from leaf-like to rod-like form of cladodes in the genus. Thus, these results indicated that the co-option and alteration of pre-existing GRC play an important role in acquisition and subsequent morphological diversification. Here, we present data of further expression analysis of A. asparagoides. The results suggested that only a part of the GRC involved in leaf development appears to have been co-opted into cladode development. Based on our study and several examples of the morphological diversification, we briefly discuss the importance of co-option of pre-existing GRC and its genetic modularity in the morphological diversity of plants during evolution.

  13. Cladodes, leaf-like organs in Asparagus, show the significance of co-option of pre-existing genetic regulatory circuit for morphological diversity of plants

    PubMed Central

    Nakayama, Hokuto; Yamaguchi, Takahiro; Tsukaya, Hirokazu

    2012-01-01

    Plants in the genus Asparagus have determinate leaf-like organs called cladodes in the position of leaf axils. Because of their leaf-like morphology, axillary position, and morphological variation, it has been unclear how this unusual organ has evolved and diversified. In the previous study, we have shown that cladodes in the genus Asparagus are modified axillary shoots and proposed a model that cladodes have arisen by co-option and deployment of genetic regulatory circuit (GRC) involved in leaf development. Moreover, we proposed that the alteration of the expression pattern of genes involved in establishment of adaxial/abaxial polarity has led to the morphological diversification from leaf-like to rod-like form of cladodes in the genus. Thus, these results indicated that the co-option and alteration of pre-existing GRC play an important role in acquisition and subsequent morphological diversification. Here, we present data of further expression analysis of A. asparagoides. The results suggested that only a part of the GRC involved in leaf development appears to have been co-opted into cladode development. Based on our study and several examples of the morphological diversification, we briefly discuss the importance of co-option of pre-existing GRC and its genetic modularity in the morphological diversity of plants during evolution. PMID:22836497

  14. C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis

    PubMed Central

    van Oevelen, Chris; Collombet, Samuel; Vicent, Guillermo; Hoogenkamp, Maarten; Lepoivre, Cyrille; Badeaux, Aimee; Bussmann, Lars; Sardina, Jose Luis; Thieffry, Denis; Beato, Miguel; Shi, Yang; Bonifer, Constanze; Graf, Thomas

    2015-01-01

    Summary Transcription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation, C/EBPα binds to two types of myeloid enhancers in B cells: pre-existing enhancers that are bound by PU.1, providing a platform for incoming C/EBPα; and de novo enhancers that are targeted by C/EBPα, acting as a pioneer factor for subsequent binding by PU.1. The order of factor binding dictates the upregulation kinetics of nearby genes. Pre-existing enhancers are broadly active throughout the hematopoietic lineage tree, including B cells. In contrast, de novo enhancers are silent in most cell types except in myeloid cells where they become activated by C/EBP factors. Our data suggest that C/EBPα recapitulates physiological developmental processes by short-circuiting two macrophage enhancer pathways in pre-B cells. PMID:26235892

  15. C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis.

    PubMed

    van Oevelen, Chris; Collombet, Samuel; Vicent, Guillermo; Hoogenkamp, Maarten; Lepoivre, Cyrille; Badeaux, Aimee; Bussmann, Lars; Sardina, Jose Luis; Thieffry, Denis; Beato, Miguel; Shi, Yang; Bonifer, Constanze; Graf, Thomas

    2015-08-11

    Transcription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation, C/EBPα binds to two types of myeloid enhancers in B cells: pre-existing enhancers that are bound by PU.1, providing a platform for incoming C/EBPα; and de novo enhancers that are targeted by C/EBPα, acting as a pioneer factor for subsequent binding by PU.1. The order of factor binding dictates the upregulation kinetics of nearby genes. Pre-existing enhancers are broadly active throughout the hematopoietic lineage tree, including B cells. In contrast, de novo enhancers are silent in most cell types except in myeloid cells where they become activated by C/EBP factors. Our data suggest that C/EBPα recapitulates physiological developmental processes by short-circuiting two macrophage enhancer pathways in pre-B cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Reduction in noise-induced functional loss of the cochleae in mice with pre-existing cochlear dysfunction due to genetic interference of prestin.

    PubMed

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation.

  17. Ecthyma gangrenosum in a 3-month-old, previously healthy infant

    PubMed Central

    Zhang, Xiao-ting; Jin, Wan-wan; Ma, Xin-hua; Yu, Hai-feng; Tang, Xu-hua

    2017-01-01

    Abstract Rationale: Ecthyma gangrenosum (EG) is an aggressive cutaneous disease caused by local or systemic infection with Pseudomonas aeruginosa. EG is characterized by cutaneous manifestations ranging from nodule and papule, to necrotic ulceration with surrounding erythema, especially with black eschar or central crust. EG presents with characteristic skin lesions which is important to establish diagnosis of sepsis caused by P aeruginosa, a serious condition that can be treated efficiently if diagnosed early. Patient concerns: A 3-month-old female infant was presented with characteristic skin lesions of EG and developed sepsis 3 days later. Diagnoses: Ecthyma gangrenosum and sepsis caused by Pseudomonas aeruginosa. Interventions: Meropenem was used in combination with ceftazidime at first and excision of necrotic skin lesions was performed later. Outcomes: Cure. Lessons: Early recognition of EG plays an important role in providing appropriate empiric antibiotic treatment at early stage of sepsis, and improves the prognosis. Surgical excision may be helpful if no improvement was achieved via antibiotic treatment. PMID:28272221

  18. Effects of pre-existing ice crystals on cirrus clouds and comparison between different ice nucleation parameterizations with the Community Atmosphere Model (CAM5)

    SciTech Connect

    Shi, Xiangjun; Liu, Xiaohong; Zhang, Kai

    2015-02-11

    In order to improve the treatment of ice nucleation in a more realistic manner in the Community Atmosphere Model version 5.3 (CAM5.3), the effects of pre-existing ice crystals on ice nucleation in cirrus clouds are considered. In addition, by considering the in-cloud variability in ice saturation ratio, homogeneous nucleation takes place spatially only in a portion of the cirrus cloud rather than in the whole area of the cirrus cloud. Compared to observations, the ice number concentrations and the probability distributions of ice number concentration are both improved with the updated treatment. The pre-existing ice crystals significantly reduce ice number concentrations in cirrus clouds, especially at mid- to high latitudes in the upper troposphere (by a factor of ~10). Furthermore, the contribution of heterogeneous ice nucleation to cirrus ice crystal number increases considerably.

    Besides the default ice nucleation parameterization of Liu and Penner (2005, hereafter LP) in CAM5.3, two other ice nucleation parameterizations of Barahona and Nenes (2009, hereafter BN) and Kärcher et al. (2006, hereafter KL) are implemented in CAM5.3 for the comparison. In-cloud ice crystal number concentration, percentage contribution from heterogeneous ice nucleation to total ice crystal number, and pre-existing ice effects simulated by the three ice nucleation parameterizations have similar patterns in the simulations with present-day aerosol emissions. However, the change (present-day minus pre-industrial times) in global annual mean column ice number concentration from the KL parameterization (3.24 × 106 m-2) is less than that from the LP (8.46 × 106 m-2) and BN (5.62 × 106 m-2) parameterizations. As a result, the experiment using the KL parameterization predicts a much smaller anthropogenic aerosol long-wave indirect forcing (0.24 W m-2) than that using the LP (0.46 W m−2

  19. Effects of pre-existing ice crystals on cirrus clouds and comparison between different ice nucleation parameterizations with the Community Atmosphere Model (CAM5)

    DOE PAGES

    Shi, Xiangjun; Liu, Xiaohong; Zhang, Kai

    2015-02-11

    In order to improve the treatment of ice nucleation in a more realistic manner in the Community Atmosphere Model version 5.3 (CAM5.3), the effects of pre-existing ice crystals on ice nucleation in cirrus clouds are considered. In addition, by considering the in-cloud variability in ice saturation ratio, homogeneous nucleation takes place spatially only in a portion of the cirrus cloud rather than in the whole area of the cirrus cloud. Compared to observations, the ice number concentrations and the probability distributions of ice number concentration are both improved with the updated treatment. The pre-existing ice crystals significantly reduce ice numbermore » concentrations in cirrus clouds, especially at mid- to high latitudes in the upper troposphere (by a factor of ~10). Furthermore, the contribution of heterogeneous ice nucleation to cirrus ice crystal number increases considerably. Besides the default ice nucleation parameterization of Liu and Penner (2005, hereafter LP) in CAM5.3, two other ice nucleation parameterizations of Barahona and Nenes (2009, hereafter BN) and Kärcher et al. (2006, hereafter KL) are implemented in CAM5.3 for the comparison. In-cloud ice crystal number concentration, percentage contribution from heterogeneous ice nucleation to total ice crystal number, and pre-existing ice effects simulated by the three ice nucleation parameterizations have similar patterns in the simulations with present-day aerosol emissions. However, the change (present-day minus pre-industrial times) in global annual mean column ice number concentration from the KL parameterization (3.24 × 106 m-2) is less than that from the LP (8.46 × 106 m-2) and BN (5.62 × 106 m-2) parameterizations. As a result, the experiment using the KL parameterization predicts a much smaller anthropogenic aerosol long-wave indirect forcing (0.24 W m-2) than that using the LP (0.46 W m−2) and BN (0.39 W m-2) parameterizations.« less

  20. Scrum kidney: epidemic pyoderma caused by a nephritogenic Streptococcus pyogenes in a rugby team.

    PubMed

    Ludlam, H; Cookson, B

    1986-08-09

    In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match.

  1. [Effect of imunofan on several indexes of immunity and pyoderma incidence among cadets of educational institutes].

    PubMed

    Mar'in, G G; Akimkin, V G; Novikov, V A; Tutel'ian, A V; Stepanov, O G; Kornilov, A B; Salmina, T A

    2009-09-01

    It was discovered that during the first several months military service men have suppression of several indexes of immunity and a high level of morbidity by pyoderma. Was shown a high effectiveness of immunomodulatory agent Imunofan on correction of immunity status of servicemen and decrease of morbidity by pyoderma (more than on threefold): the effectiveness index is 3,25, the defense index is 69,2%. In addition, it was marked hepatitis- and stress-protect effect of the agent. It was made a conclusion about necessity of further examination of questions of correction of immunity status of military servicemen for the purpose of decrease of morbidity by infections, actual for studying units of the Armed Forces of RF.

  2. Reactivation of pre-existing mechanical anisotropies during polyphase tectonic evolution: slip tendency analysis as a tool to constrain mechanical properties of rocks

    NASA Astrophysics Data System (ADS)

    Traforti, Anna; Bistacchi, Andrea; Massironi, Matteo; Zampieri, Dario; Di Toro, Giulio

    2017-04-01

    Intracontinental deformation within the upper crust is accommodated by nucleation of new faults (generally satisfying the Anderson's theory of faulting) or brittle reactivation of pre-existing anisotropies when certain conditions are met. How prone to reactivation an existing mechanical anisotropy or discontinuity is, depends on its mechanical strength compared to that of the intact rock and on its orientation with respect to the regional stress field. In this study, we consider how different rock types (i.e. anisotropic vs. isotropic) are deformed during a well-constrained brittle polyphase tectonic evolution to derive the mechanical strength of pre-existing anisotropies and discontinuities (i.e. metamorphic foliations and inherited faults/fractures). The analysis has been carried out in the Eastern Sierras Pampeanas of Central Argentina. These are a series of basement ranges of the Andean foreland, which show compelling evidence of a long-lasting brittle deformation history from the Early Carboniferous to Present time, with three main deformational events (Early Triassic to Early Jurassic NE-SW extension, Early Cretaceous NW-SE extension and Miocene to Present ENE-WNW compression). The study area includes both isotropic granitic bodies and anisotropic phyllosilicate-bearing rocks (gneisses and phyllites). In this environment, each deformation phase causes significant reactivation of the inherited structures and rheological anisotropies, or alternatively formation of neo-formed Andersonian faults, thus providing a multidirectional probing of mechanical properties of these rocks. A meso- and micro-structural analysis of brittle reactivation of metamorphic foliation or inherited faults/fractures revealed that different rock types present remarkable differences in the style of deformation (i.e., phyllite foliation is reactivated during the last compressional phase and cut by newly-formed Andersonian faults/fractures during the first two extensional regimes; instead

  3. Early Colonoscopy Confers Survival Benefits on Colon Cancer Patients with Pre-Existing Iron Deficiency Anemia: A Nationwide Population-Based Study

    PubMed Central

    Teng, Chieh-Lin Jerry; Yu, Jui-Ting; Chen, Yi-Huei; Lin, Ching-Heng; Hwang, Wen-Li

    2014-01-01

    This study aimed to examine the prognostic significance of pre-existing iron deficiency anemia (IDA) and the benefits of early colonoscopy in patients with colon cancer, since these have not been clearly established to date. Using the Taiwanese National Health Insurance Research Database, we retrieved and retrospectively reviewed the records of patients aged ≥55 years who were diagnosed with colon cancer between 2000 and 2005. The patient cohort was divided into two groups: patients with (n = 1,260) or without (n = 15,912) an IDA diagnosis during ≤18 months preceding the date of colon cancer diagnosis. We found that diabetes (27.9% vs. 20.3%, p<0.0001), cardiovascular disease (61.6% vs. 54.7%, p<0.001), and chronic kidney disease (4.6% vs. 2.2%, p<0.0001) were more common among patients with IDA than among those without IDA. The median overall survival times for patients with IDA and those without IDA were 4.6 and 5.7 years, respectively (p = 0.002). Patients who underwent colonoscopy ≤30 days, 31–90, and ≥91 days after IDA diagnosis showed median overall survival times of 5.79, 4.43, and 4.04 years, respectively (p = 0.003). Delayed colonoscopy was an independent factor associated with poor overall survival (adjusted hazard ratio, 1.28; 95% confidence interval, 1.07–1.53; p = 0.01). In conclusion, colon cancer patients with IDA were more likely to experience comorbidities than were those without IDA. Pre-existing IDA was a poor prognostic factor in adult men and postmenopausal women who had colon cancer. Early colonoscopy could improve overall survival possibly by facilitating early diagnosis and treatment. PMID:24466209

  4. Early colonoscopy confers survival benefits on colon cancer patients with pre-existing iron deficiency anemia: a nationwide population-based study.

    PubMed

    Teng, Chieh-Lin Jerry; Yu, Jui-Ting; Chen, Yi-Huei; Lin, Ching-Heng; Hwang, Wen-Li

    2014-01-01

    This study aimed to examine the prognostic significance of pre-existing iron deficiency anemia (IDA) and the benefits of early colonoscopy in patients with colon cancer, since these have not been clearly established to date. Using the Taiwanese National Health Insurance Research Database, we retrieved and retrospectively reviewed the records of patients aged ≥ 55 years who were diagnosed with colon cancer between 2000 and 2005. The patient cohort was divided into two groups: patients with (n = 1,260) or without (n = 15,912) an IDA diagnosis during ≤ 18 months preceding the date of colon cancer diagnosis. We found that diabetes (27.9% vs. 20.3%, p<0.0001), cardiovascular disease (61.6% vs. 54.7%, p<0.001), and chronic kidney disease (4.6% vs. 2.2%, p<0.0001) were more common among patients with IDA than among those without IDA. The median overall survival times for patients with IDA and those without IDA were 4.6 and 5.7 years, respectively (p = 0.002). Patients who underwent colonoscopy ≤ 30 days, 31-90, and ≥ 91 days after IDA diagnosis showed median overall survival times of 5.79, 4.43, and 4.04 years, respectively (p = 0.003). Delayed colonoscopy was an independent factor associated with poor overall survival (adjusted hazard ratio, 1.28; 95% confidence interval, 1.07-1.53; p = 0.01). In conclusion, colon cancer patients with IDA were more likely to experience comorbidities than were those without IDA. Pre-existing IDA was a poor prognostic factor in adult men and postmenopausal women who had colon cancer. Early colonoscopy could improve overall survival possibly by facilitating early diagnosis and treatment.

  5. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study.

    PubMed

    Grönlund, O; Herweijer, E; Sundström, K; Arnheim-Dahlström, L

    2016-12-01

    To assess whether quadrivalent human papillomavirus (qHPV) vaccination is associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. This register-based open cohort study included all girls and women between 10 and 30 years of age in Sweden in 2006-2012 diagnosed with at least one of 49 prespecified autoimmune diseases (n = 70 265). Incidence rate ratios were estimated for new-onset autoimmune disease within 180 days of qHPV vaccination using Poisson regression adjusting for, country of birth, parental country of birth, parental income and parental education. A total of 70 265 girls and women had at least one of the 49 predefined autoimmune diseases; 16% of these individuals received at least one dose of qHPV vaccine. In unvaccinated girls and women, 5428 new-onset autoimmune diseases were observed during 245 807 person-years at a rate of 22.1 (95% CI 21.5-22.7) new events per 1000 person-years. In vaccinated girls and women, there were 124 new events during 7848 person-years at a rate of 15.8 (95% CI 13.2-18.8) per 1000 person-years. There was no increase in the incidence of new-onset autoimmune disease associated with qHPV vaccination during the risk period; on the contrary, we found a slightly reduced risk (incidence rate ratio 0.77, 95% CI 0.65-0.93). In this nationwide study, qHPV vaccination was not associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  6. Nature or nurture: the effect of undergraduate rural clinical rotations on pre-existent rural career choice likelihood as measured by the SOMERS Index.

    PubMed

    Somers, George T; Spencer, Ryan J

    2012-04-01

    Do undergraduate rural clinical rotations increase the likelihood of medical students to choose a rural career once pre-existent likelihood is accounted for? A prospective, controlled quasi-experiment using self-paired scores on the SOMERS Index of rural career choice likelihood, before and after 3 years of clinical rotations in either mainly rural or mainly urban locations. Monash University medical school, Australia. Fifty-eight undergraduate-entry medical students (35% of the 2002 entry class). The SOMERS Index of rural career choice likelihood and its component indicators. There was an overall decline in SOMERS Index score (22%) and in each of its components (12-41%). Graduating students who attended rural rotations were more likely to choose a rural career on graduation (difference in SOMERS score: 24.1 (95% CI, 15.0-33.3) P<0.0001); however, at entry, students choosing rural rotations had an even greater SOMERS score (difference: 27.1 (95% CI, 18.2-36.1) P<0.0001). Self-paired pre-post reductions in likelihood were not affected by attending mainly rural or urban rotations, nor were there differences based on rural background alone or sex. While rural rotations are an important component of undergraduate medical training, it is the nature of the students choosing to study in rural locations rather than experiences during the course that is the greater influence on rural career choice. In order to improve the rural medical workforce crisis, medical schools should attract more students with pre-existent likelihood to choose a rural career. The SOMERS Index was found to be a useful tool for this quantitative analysis. © 2012 The Authors. Australian Journal of Rural Health © 2012 National Rural Health Alliance Inc.

  7. Underrepresentation of patients with pre-existing cognitive impairment in pharmaceutical trials on prophylactic or therapeutic treatments for delirium: a systematic review.

    PubMed

    de Jonghe, Annemarieke; van de Glind, Esther M M; van Munster, Barbara C; de Rooij, Sophia E

    2014-03-01

    Representation of hospitalized patients with pre-existing cognitive impairment in pharmaceutical delirium trials is important because these patients are at high risk for developing delirium. The aim of this systematic review is to investigate whether patients with cognitive impairment were included in studies on pharmacological prophylaxis or treatment of delirium and to explore the motivations for their exclusion (if they were excluded). This study was a systematic review. A MEDLINE search was performed for publications dated from 1 January 1985 to 15 November 2012. Randomized and non-randomized controlled trials that investigated medication to prevent or treat delirium were included. The number of patients with cognitive impairment was counted, and if they were excluded, motivations were noted. The search yielded 4293 hits, ultimately resulting in 31 studies that met the inclusion criteria. Of these, five studies explicitly mentioned the percentage of patients with cognitive impairment that were included. These patients comprised a total of 8% (n = 279 patients) of the 3476 patients included in all 31 studies. Ten studies might have included cognitively impaired patients but did not mention the exact percentage, and sixteen studies excluded all patients with cognitive impairment. The motivations for exclusion varied, but most were related to the influence of dementia on delirium. The exclusion of patients with pre-existing cognitive impairment hampers the generalizability of the results of these trials and leaves clinicians with limited evidence about the pharmacological treatment of this group of vulnerable patients who have an increased risk of side effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Vaccines expressing the innate immune modulator EAT-2 elicit potent effector memory T lymphocyte responses despite pre-existing vaccine immunity.

    PubMed

    Aldhamen, Yasser Ali; Seregin, Sergey S; Schuldt, Nathaniel J; Rastall, David P W; Liu, Chyong-Jy J; Godbehere, Sarah; Amalfitano, Andrea

    2012-08-01

    The mixed results from recent vaccine clinical trials targeting HIV-1 justify the need to enhance the potency of HIV-1 vaccine platforms in general. Use of first-generation recombinant adenovirus serotype 5 (rAd5) platforms failed to protect vaccinees from HIV-1 infection. One hypothesis is that the rAd5-based vaccine failed due to the presence of pre-existing Ad5 immunity in many vaccines. We recently confirmed that EAT-2-expressing rAd5 vectors uniquely activate the innate immune system and improve cellular immune responses against rAd5-expressed Ags, inclusive of HIV/Gag. In this study, we report that use of the rAd5-EAT-2 vaccine can also induce potent cellular immune responses to HIV-1 Ags despite the presence of Ad5-specific immunity. Compared to controls expressing a mutant SH2 domain form of EAT-2, Ad5 immune mice vaccinated with an rAd5-wild-type EAT-2 HIV/Gag-specific vaccine formulation significantly facilitated the induction of several arms of the innate immune system. These responses positively correlated with an improved ability of the vaccine to induce stronger effector memory T cell-biased, cellular immune responses to a coexpressed Ag despite pre-existing anti-Ad5 immunity. Moreover, inclusion of EAT-2 in the vaccine mixture improves the generation of polyfunctional cytolytic CD8(+) T cell responses as characterized by enhanced production of IFN-γ, TNF-α, cytotoxic degranulation, and increased in vivo cytolytic activity. These data suggest a new approach whereby inclusion of EAT-2 expression in stringent human vaccination applications can provide a more effective vaccine against HIV-1 specifically in Ad5 immune subjects.

  9. Risk factors for adjacent segment pathology requiring additional surgery after single-level spinal fusion: impact of pre-existing spinal stenosis demonstrated by preoperative myelography.

    PubMed

    Yugué, Itaru; Okada, Seiji; Masuda, Muneaki; Ueta, Takayoshi; Maeda, Takeshi; Shiba, Keiichiro

    2016-05-01

    We determined the incidence of and risk factors for clinical adjacent segment pathology (C-ASP) requiring additional surgeries among patients previously treated with one-segment lumbar decompression and fusion surgery. We retrospectively analysed 161 consecutive patients who underwent one-segment lumbar decompression and fusion surgery for L4 degenerative spondylolisthesis. Patient age, sex, body mass index (BMI), facet orientation and tropism, laminar inclination angle, spinal canal stenosis ratio [on myelography and magnetic resonance imaging (MRI)], preoperative adjacent segment instability, arthrodesis type, pseudarthrosis, segmental lordosis at L4-5, and the present L4 slip were evaluated by a log-rank test using the Kaplan-Meier method. A multivariate Cox proportional-hazards model was used to analyse all factors found significant by the log-rank test. Of 161 patients, 22 patients (13.7 %) had additional surgeries at cranial segments located adjacent to the index surgery's location. Pre-existing canal stenosis ≥47 % at the adjacent segment on myelography, greater facet tropism, and high BMI were significant risk factors for C-ASP. The estimated incidences at 10 years postoperatively for each of these factors were 51.3, 39.6, and 32.5 %, and the risks for C-ASP were 4.9, 3.7, and, 3.1 times higher than their counterparts, respectively. Notably, spinal canal stenosis on myelography, but not on MRI, was found to be a significant risk factor for C-ASP (log-rank test P < 0.0001 and 0.299, respectively). Pre-existing spinal stenosis, greater facet tropism, and higher BMI significantly increased C-ASP risk. Myelography is a more accurate method for detecting latent spinal canal stenosis as a risk factor for C-ASP.

  10. Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.

    PubMed

    Brestoff, Jonathan R; Brodsky, Tim; Sosinsky, Alexandra Z; McLoughlin, Ryan; Stansky, Elena; Fussell, Leila; Sheppard, Aaron; DiSanto-Rose, Maria; Kershaw, Erin E; Reynolds, Thomas H

    2015-01-01

    The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression.

  11. The impact of focusing a program to prevent heavier drinking on a pre-existing phenotype, the low level of response to alcohol.

    PubMed

    Schuckit, Marc A; Smith, Tom L; Kalmijn, Jelger; Skidmore, Jessica; Clausen, Peyton; Shafir, Alexandra; Saunders, Gretchen; Bystritsky, Hannah; Fromme, Kim

    2015-02-01

    Heavy drinking is common during transitions from high school to college. Optimal programs for diminishing risks for high alcohol consumption often tailor the approach to the specific needs of students. This study describes the results of an Internet-based prevention protocol that tailors the information to the risk associated with a pre-existing phenotype, the Low level of Response (Low LR) to alcohol. Using stratified random assignment, 454 freshmen with Low and High LR values were assigned to 2 education groups (LR-based where all examples were given the context of the Low LR model of heavy drinking or a State Of The Art (SOTA) Group where the same lessons were taught but without an emphasis on LR) or a no-intervention Control Group. Individuals in the 2 education groups viewed 50-minute online videos once per week for 4 weeks. Changes in drinking patterns were assessed at Baseline, 4 weeks, and 8 weeks using a 2 (LR status) by 3 (education group) by 3 (time points) analysis of variance, with additional tests for ethnicity and sex. Low LR participants tended to decrease their usual (p < 0.06) and maximum (p < 0.05) drinks per occasion most prominently when assigned to the LR-based protocol, while those with High LRs improved more in the SOTA Group. The most robust differences were seen when controlling for ethnicity. The effect sizes were small to medium. These results support the advantages of carrying out prevention via the Internet and in tailoring the approach to a pre-existing phenotype. Copyright © 2015 by the Research Society on Alcoholism.

  12. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    PubMed

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes; Bassi, Maria Rosaria; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2012-01-01

    Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  13. A distinct pre-existing inflammatory tumour microenvironment is associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer

    PubMed Central

    Koti, M; Siu, A; Clément, I; Bidarimath, M; Turashvili, G; Edwards, A; Rahimi, K; Masson, A-M M; Squire, J A

    2015-01-01

    Background: Chemotherapy resistance is a major determinant of poor overall survival rates in high-grade serous ovarian cancer (HGSC). We have previously shown that gene expression alterations affecting the NF-κB pathway characterise chemotherapy resistance in HGSC, suggesting that the regulation of an immune response may be associated with this phenotype. Methods: Given that intrinsic drug resistance pre-exists and is governed by both tumour and host factors, the current study was performed to examine the cross-talk between tumour inflammatory microenvironment and cancer cells, and their roles in mediating differential chemotherapy response in HGSC patients. Expression profiling of a panel of 184 inflammation-related genes was performed in 15 chemoresistant and 19 chemosensitive HGSC tumours using the NanoString nCounter platform. Results: A total of 11 significantly differentially expressed genes were found to distinguish the two groups. As STAT1 was the most significantly differentially expressed gene (P=0.003), we validated the expression of STAT1 protein by immunohistochemistry using an independent cohort of 183 (52 resistant and 131 sensitive) HGSC cases on a primary tumour tissue microarray. Relative expression levels were subjected to Kaplan–Meier survival analysis and Cox proportional hazard regression models. Conclusions: This study confirms that higher STAT1 expression is significantly associated with increased progression-free survival and that this protein together with other mediators of tumour–host microenvironment can be applied as a novel response predictive biomarker in HGSC. Furthermore, an overall underactive immune microenvironment suggests that the pre-existing state of the tumour immune microenvironment could determine response to chemotherapy in HGSC. PMID:25826225

  14. Reactivation of compressional pre-existing structures in an extensional regime by wastewater re-injection induced seismicity: a Southern Appennine (Italy) oilfield case study

    NASA Astrophysics Data System (ADS)

    Buttinelli, M.; Improta, L.; Bagh, S.; Chiarabba, C.

    2015-12-01

    The Val d'Agri Quaternary basin is located within the Southern Apennine extensional belt, hosting the largest oilfield in Europe. Since 2006 wastewaters coming from oil production were re-injected by a single disposal well into the reservoir, represented by the carbonates of the Apulian platform. Consequently, induced micro-seismicity (219 events, ML < 2.3) was recorded close to the beginning of injection and within 5 km of the well. Afterwards, a detailed analysis of the oilfield underground dataset was performed to define a 3D geological model of the injection site. A pre-existing thrust system inherited by a Plio-Pleistocene compressional tectonic phase mainly constituted by NE-verging high-angle thrusts and SW-verging back-thrusts interesting the Apulian carbonates was interpreted. Below the injection well a mainly E-dipping back-thrust completely developed between two major thrusts can be modeled. The depth conversions of seismic interpretation based on sonic logs, VSP and seismic check-shots highlighted that the back-thrust geometry is compatible with accurate 3D absolute location and high precision relative location of induced events. Such analysis also show that wastewater injection firstly caused the reactivation of the deep portion of the back-thrust, and then seismicity mainly migrated up-dip toward shallower depths and interesting some portions of other faults, but remaining almost confined within the reservoir volume, and close to the injection well. These combined results also suggest that induced events presumably occurred on a small and high-permeability patch of the fault zone, favorably oriented with respect to the present-day SW-NE trending extensional stress field. Results can be read in the light of understanding the impact that induced seismicity due to the reactivation of pre-existing/inactive faults might have on seismic hazard and seismogenic potential evaluations, especially in tectonically active areas like Italy

  15. A distinct pre-existing inflammatory tumour microenvironment is associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer.

    PubMed

    Koti, M; Siu, A; Clément, I; Bidarimath, M; Turashvili, G; Edwards, A; Rahimi, K; Mes-Masson, A-M; Masson, A-M M; Squire, J A

    2015-03-31

    Chemotherapy resistance is a major determinant of poor overall survival rates in high-grade serous ovarian cancer (HGSC). We have previously shown that gene expression alterations affecting the NF-κB pathway characterise chemotherapy resistance in HGSC, suggesting that the regulation of an immune response may be associated with this phenotype. Given that intrinsic drug resistance pre-exists and is governed by both tumour and host factors, the current study was performed to examine the cross-talk between tumour inflammatory microenvironment and cancer cells, and their roles in mediating differential chemotherapy response in HGSC patients. Expression profiling of a panel of 184 inflammation-related genes was performed in 15 chemoresistant and 19 chemosensitive HGSC tumours using the NanoString nCounter platform. A total of 11 significantly differentially expressed genes were found to distinguish the two groups. As STAT1 was the most significantly differentially expressed gene (P=0.003), we validated the expression of STAT1 protein by immunohistochemistry using an independent cohort of 183 (52 resistant and 131 sensitive) HGSC cases on a primary tumour tissue microarray. Relative expression levels were subjected to Kaplan-Meier survival analysis and Cox proportional hazard regression models. This study confirms that higher STAT1 expression is significantly associated with increased progression-free survival and that this protein together with other mediators of tumour-host microenvironment can be applied as a novel response predictive biomarker in HGSC. Furthermore, an overall underactive immune microenvironment suggests that the pre-existing state of the tumour immune microenvironment could determine response to chemotherapy in HGSC.

  16. Protective efficacy of a single immunization with capripoxvirus-vectored recombinant peste des petits ruminants vaccines in presence of pre-existing immunity.

    PubMed

    Caufour, Philippe; Rufael, Tesfaye; Lamien, Charles Euloge; Lancelot, Renaud; Kidane, Menbere; Awel, Dino; Sertse, Tefera; Kwiatek, Olivier; Libeau, Geneviève; Sahle, Mesfin; Diallo, Adama; Albina, Emmanuel

    2014-06-24

    Sheeppox, goatpox and peste des petits ruminants (PPR) are highly contagious ruminant diseases widely distributed in Africa, the Middle East and Asia. Capripoxvirus (CPV)-vectored recombinant PPR vaccines (rCPV-PPR vaccines), which have been developed and shown to protect against both Capripox (CP) and PPR, would be critical tools in the control of these important diseases. In most parts of the world, these disease distributions overlap each other leaving concerns about the potential impact that pre-existing immunity against either disease may have on the protective efficacy of these bivalent rCPV-PPR vaccines. Currently, this question has not been indisputably addressed. Therefore, we undertook this study, under experimental conditions designed for the context of mass vaccination campaigns of small ruminants, using the two CPV recombinants (Kenya sheep-1 (KS-1) strain-based constructs) developed previously in our laboratory. Pre-existing immunity was first induced by immunization either with an attenuated CPV vaccine strain (KS-1) or the attenuated PPRV vaccine strain (Nigeria 75/1) and animals were thereafter inoculated once subcutaneously with a mixture of CPV recombinants expressing either the hemagglutinin (H) or the fusion (F) protein gene of PPRV (10(3) TCID50/animal of each). Finally, these animals were challenged with a virulent CPV strain followed by a virulent PPRV strain 3 weeks later. Our study demonstrated full protection against CP for vaccinated animals with prior exposure to PPRV and a partial protection against PPR for vaccinated animals with prior exposure to CPV. The latter animals exhibited a mild clinical form of PPR and did not show any post-challenge anamnestic neutralizing antibody response against PPRV. The implications of these results are discussed herein and suggestions made for future research regarding the development of CPV-vectored vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid Leukemia

    PubMed Central

    Skaggs, Brian; Gorre, Mercedes; Sawyers, Charles L.; Michor, Franziska

    2011-01-01

    Chronic myeloid leukemia (CML) is the first human malignancy to be successfully treated with a small molecule inhibitor, imatinib, targeting a mutant oncoprotein (BCR-ABL). Despite its successes, acquired resistance to imatinib leads to reduced drug efficacy and frequent progression of disease. Understanding the characteristics of pre-existing resistant cells is important for evaluating the benefits of first-line combination therapy with second generation inhibitors. However, due to limitations of assay sensitivity, determining the existence and characteristics of resistant cell clones at the start of therapy is difficult. Here we combined a mathematical modeling approach using branching processes with experimental data on the fitness changes (i.e., changes in net reproductive rate) conferred by BCR-ABL kinase domain mutations to investigate the likelihood, composition, and diversity of pre-existing resistance. Furthermore, we studied the impact of these factors on the response to tyrosine kinase inhibitors. Our approach predicts that in most patients, there is at most one resistant clone present at the time of diagnosis of their disease. Interestingly, patients are no more likely to harbor the most aggressive, pan-resistant T315I mutation than any other resistance mutation; however, T315I cells on average establish larger-sized clones at the time of diagnosis. We established that for patients diagnosed late, the relative benefit of combination therapy over monotherapy with imatinib is significant, while this benefit is modest for patients with a typically early diagnosis time. These findings, after pre-clinical validation, will have implications for the clinical management of CML: we recommend that patients with advanced-phase disease be treated with combination therapy with at least two tyrosine kinase inhibitors. PMID:22140458

  18. Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine.

    PubMed

    Chuan, Yap P; Rivera-Hernandez, Tania; Wibowo, Nani; Connors, Natalie K; Wu, Yang; Hughes, Fiona K; Lua, Linda H L; Middelberg, Anton P J

    2013-09-01

    Modularization of a peptide antigen for presentation on a microbially synthesized murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative for rapid and low-cost vaccine delivery at a global scale. In this approach, heterologous modules containing peptide antigenic elements are fused to and displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via ordered and densely repeated presentation of the modules. This study addresses two key engineering questions pertaining to this platform, exploring the effects of (i) pre-existing carrier-specific immunity on modular VLP vaccine effectiveness and (ii) increase in the antigenic element number per VLP on peptide-specific immune response. These effects were studied in a mouse model and with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen, J8i. The data presented here demonstrate that immunization with a modular VLP could induce high levels of J8i-specific antibodies despite a strong pre-existing anti-carrier immune response. Doubling of the J8i antigenic element number per VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the strategy, when used in conjunction with increased VLP dose, could effectively increase the peptide dose up to 10-fold, leading to a significantly higher J8i-specific antibody titer. This study further supports feasibility of the MuPyV modular VLP vaccine platform by showing that, in the absence of adjuvant, modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to raise a high level of peptide-specific IgGs indicative of bactericidal activity.

  19. Pyoderma Gangrenosum–Like Ulcer in a Patient With X-Linked Agammaglobulinemia

    PubMed Central

    Murray, Patrick R.; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B.; Ecker, David J.; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L.

    2011-01-01

    Background Pyoderma gangrenosum–like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient’s culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. Observation An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when sub-cultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. Conclusions This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum–like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum–like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy. PMID:20479300

  20. Antimicrobial susceptibility profiles of Staphylococcus intermedius isolates from clinical cases of canine pyoderma in South Africa.

    PubMed

    Blunt, Catherine A; van Vuuren, Moritz; Picard, Jacqueline

    2013-05-16

    Successful treatment of canine pyoderma has become compromised owing to the development of antimicrobial resistance with accompanying recurrence of infection. Canine skin samples submitted to a veterinary diagnostic laboratory for microbiological culture and sensitivity between January 2007 and June 2010, from which Staphylococcus intermedius was isolated, were selected for this investigation. Antimicrobial resistance of S. intermedius was most prevalent with reference to ampicillin followed by resistance to tetracycline and then potentiated sulphonamides. In general, antimicrobial resistance was low and very few methicillin-resistant isolates were detected. Temporal trends were not noted, except for ampicillin, with isolates becoming more susceptible, and potentiated sulphonamides (co-trimoxazole), with isolates becoming more resistant. In general, both the Kirby-Bauer disc diffusion and broth dilution minimum inhibitory concentration tests yielded similar results for the antimicrobial agents tested. The main difference was evident in the over-estimation of resistance by the Kirby-Bauer test for ampicillin, co-trimoxazole, penicillin and doxycycline. Knowledge of trends in bacterial resistance is important for veterinarians when presented with canine pyoderma. Analysis of antimicrobial susceptibility profiles of S. intermedius isolated from canine pyodermas will guide veterinarians' use of the most appropriate agent and encourage prudent use of antimicrobials in companion animals.

  1. The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma

    PubMed Central

    Bowen, Asha C.; Mahé, Antoine; Hay, Roderick J.; Andrews, Ross M.; Steer, Andrew C.; Tong, Steven Y. C.; Carapetis, Jonathan R.

    2015-01-01

    Objective We conducted a comprehensive, systematic review of the global childhood population prevalence of impetigo and the broader condition pyoderma. Methods PubMed was systematically searched for impetigo or pyoderma studies published between January 1 1970 and September 30 2014. Two independent reviewers extracted data from each relevant article on the prevalence of impetigo. Findings Sixty-six articles relating to 89 studies met our inclusion criteria. Based on population surveillance, 82 studies included data on 145,028 children assessed for pyoderma or impetigo. Median childhood prevalence was 12·3% (IQR 4·2–19·4%). Fifty-eight (65%) studies were from low or low-middle income countries, where median childhood prevalences were 8·4% (IQR 4·2–16·1%) and 14·5% (IQR 8·3–20·9%), respectively. However, the highest burden was seen in underprivileged children from marginalised communities of high-income countries; median prevalence 19·4%, (IQR 3·9–43·3%). Conclusion Based on data from studies published since 2000 from low and low-middle income countries, we estimate the global population of children suffering from impetigo at any one time to be in excess of 162 million, predominantly in tropical, resource-poor contexts. Impetigo is an under-recognised disease and in conjunction with scabies, comprises a major childhood dermatological condition with potential lifelong consequences if untreated. PMID:26317533

  2. The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma.

    PubMed

    Bowen, Asha C; Mahé, Antoine; Hay, Roderick J; Andrews, Ross M; Steer, Andrew C; Tong, Steven Y C; Carapetis, Jonathan R

    2015-01-01

    We conducted a comprehensive, systematic review of the global childhood population prevalence of impetigo and the broader condition pyoderma. PubMed was systematically searched for impetigo or pyoderma studies published between January 1 1970 and September 30 2014. Two independent reviewers extracted data from each relevant article on the prevalence of impetigo. Sixty-six articles relating to 89 studies met our inclusion criteria. Based on population surveillance, 82 studies included data on 145,028 children assessed for pyoderma or impetigo. Median childhood prevalence was 12·3% (IQR 4·2-19·4%). Fifty-eight (65%) studies were from low or low-middle income countries, where median childhood prevalences were 8·4% (IQR 4·2-16·1%) and 14·5% (IQR 8·3-20·9%), respectively. However, the highest burden was seen in underprivileged children from marginalised communities of high-income countries; median prevalence 19·4%, (IQR 3·9-43·3%). Based on data from studies published since 2000 from low and low-middle income countries, we estimate the global population of children suffering from impetigo at any one time to be in excess of 162 million, predominantly in tropical, resource-poor contexts. Impetigo is an under-recognised disease and in conjunction with scabies, comprises a major childhood dermatological condition with potential lifelong consequences if untreated.

  3. Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves' disease.

    PubMed

    Zhu, Cheng-Yao; Zhang, Guo-Xue; Yu, Zuo-Zhong; Li, Zhao-Jun; Fan, Yi-Ming

    2014-04-01

    A 35-year-old woman with postoperative recurrent Graves' disease presented with a 5-day history of a red swelling on the right cheek associated with 4 days of remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her white blood cell count, immunoglobulins, and lymphocyte subsets were unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated erythematous plaque occurred on the right leg on hospital day 3. She was treated with intravenous antibiotics with topical gentamicin, recombinant bovine basic fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The ulcer healed leaving a depressed scar at 35 days after discharge. This patient may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis in postoperative recurrent Graves' disease.

  4. Ecthyma gangrenosum, a skin manifestation of Pseudomonas aeruginosa sepsis in a previously healthy child

    PubMed Central

    Biscaye, Stephanie; Demonchy, Diane; Afanetti, Mickael; Dupont, Audrey; Haas, Herve; Tran, Antoine

    2017-01-01

    Abstract Rationale: Ecthyma gangrenosum (Eg) is a necrotic lesion that is mostly seen in immunocompromised patients. It reflects a severe sepsis, possibly caused by Pseudomonas aeruginosa (Pa). Patient concerns: A healthy 3-year-old girl admitted to the Pediatric Emergency Department presented a sepsis-associated purpura with neurological and respiratory distress. Interventions: An empiric antibiotherapy (anti-meningococcal) was prescribed. Diagnoses: Forty-eight hours after admission, blood and wound cultures were positive for Pa. As a result, the decision was made to change the antibiotic therapy. Unfortunately, on day 3, the patient died. Exhaustive immunologic tests are presently being carried out. Outcomes: Eg caused by Pa is uncommon in healthy children, and purpura sepsis is usually caused by Neisseria meningitides infection. Lessons: Eg should be recognized rapidly so that the appropriate treatment can be prescribed as quickly as possible. PMID:28079790

  5. Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients

    PubMed Central

    2014-01-01

    Introduction Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single doses of pegloticase unexpectedly induced antibodies (Ab) that bound to polyethylene glycol (PEG). We have conducted a phase 2 trial to evaluate every 3-week dosing, and to further define the Ab response to pegloticase. Organ transplant recipients were included, as they are prone to severe gout that is difficult to manage, and because treatment to prevent graft rejection might influence the immune response to pegloticase. Methods Plasma uricase activity (pUox), urate concentration (pUA), and clinical response were monitored during up to 5 infusions in 30 patients, including 7 organ transplant recipients. Depending on whether pUA <6 mg/dL was achieved and maintained, patients were classified as non (NR), persistent (PR), or transient (TR) responders. Ab to pegloticase and 10 kDa mPEG were monitored by enzyme linked immunosorbent assay and specificity was further defined. Results We observed 17 PR, 12 TR, and 1 NR; 21 patients (16 PR, 5 TR) received all 5 infusions. Over the 15-week trial, pUA in PR averaged 1.0 ± 0.4 mg/dL; T½ for pUox was approximately 13 days, and area under the curve after dose 5 was approximately 30% higher than after dose 1. PR showed clinical benefit and in some, tophi resolved. In 11 of 12 TR, pUox fell rapidly and hyperuricemia recurred before dose 2. In all TR and NR, loss of response to pegloticase was accompanied by Ab to PEG, which was pre-existing in half of those who had no prior exposure to pegloticase. No PR, and 1 one out of 7 organ transplant recipients, had a sustained Ab response to pegloticase. Conclusions Every 3-week dosing is effective and may enhance the utility of pegloticase for treating refractory gout. Ab to PEG, which were pre-existing or induced by treatment

  6. Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients.

    PubMed

    Hershfield, Michael S; Ganson, Nancy J; Kelly, Susan J; Scarlett, Edna L; Jaggers, Denise A; Sundy, John S

    2014-03-07

    Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single doses of pegloticase unexpectedly induced antibodies (Ab) that bound to polyethylene glycol (PEG). We have conducted a phase 2 trial to evaluate every 3-week dosing, and to further define the Ab response to pegloticase. Organ transplant recipients were included, as they are prone to severe gout that is difficult to manage, and because treatment to prevent graft rejection might influence the immune response to pegloticase. Plasma uricase activity (pUox), urate concentration (pUA), and clinical response were monitored during up to 5 infusions in 30 patients, including 7 organ transplant recipients. Depending on whether pUA <6 mg/dL was achieved and maintained, patients were classified as non (NR), persistent (PR), or transient (TR) responders. Ab to pegloticase and 10 kDa mPEG were monitored by enzyme linked immunosorbent assay and specificity was further defined. We observed 17 PR, 12 TR, and 1 NR; 21 patients (16 PR, 5 TR) received all 5 infusions. Over the 15-week trial, pUA in PR averaged 1.0 ± 0.4 mg/dL; T½ for pUox was approximately 13 days, and area under the curve after dose 5 was approximately 30% higher than after dose 1. PR showed clinical benefit and in some, tophi resolved. In 11 of 12 TR, pUox fell rapidly and hyperuricemia recurred before dose 2. In all TR and NR, loss of response to pegloticase was accompanied by Ab to PEG, which was pre-existing in half of those who had no prior exposure to pegloticase. No PR, and 1 one out of 7 organ transplant recipients, had a sustained Ab response to pegloticase. Every 3-week dosing is effective and may enhance the utility of pegloticase for treating refractory gout. Ab to PEG, which were pre-existing or induced by treatment, caused rapid loss of efficacy and increased

  7. The effects of aerobic- versus strength-training on body image among young women with pre-existing body image concerns.

    PubMed

    Martin Ginis, Kathleen A; Strong, Heather A; Arent, Shawn M; Bray, Steven R; Bassett-Gunter, Rebecca L

    2014-06-01

    This experiment compared the effects of aerobic-training (AT) versus strength-training (ST) on body image among young women with pre-existing body image concerns. Theory-based correlates of body image change were also examined. Participants were 46 women (M age=21.5 years), randomly assigned to an 8-week AT or ST intervention consisting of supervised exercise 3 days/week. Multidimensional measures of body image were administered pre- and post-intervention, along with measures of physical fitness, perceived fitness, and exercise self-efficacy. Women in the AT condition reported greater reductions in social physique anxiety (p=.001) and tended to report greater improvements in appearance evaluation (p=.06) than women in the ST condition. Changes in perceived fatness, perceived aerobic endurance and aerobic self-efficacy were significantly correlated with body image change (ps<.003). Results provide direction for prescribing exercise to improve body image and advancing theory to account for the effects of exercise. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Evidence for a pre-existing telomere deficit in non-clonal hematopoietic stem cells in patients with acute myeloid leukemia.

    PubMed

    Ventura Ferreira, Mónica S; Crysandt, Martina; Ziegler, Patrick; Hummel, Sebastian; Wilop, Stefan; Kirschner, Martin; Schemionek, Mirle; Jost, Edgar; Wagner, Wolfgang; Brümmendorf, Tim H; Beier, Fabian

    2017-09-01

    Telomere shortening represents an established mechanism connecting aging and cancer development. We sequentially analyzed telomere length (TL) of 49 acute myeloid leukemia (AML) patients at diagnosis (n = 24), once they achieved complete cytological remission (CCR) and/or during refractory disease or relapse and after 1-year follow-up, with all patients having at least two sequential samples. TL was analyzed by monochrome multiplex quantitative polymerase chain reaction. We have observed substantially shortened TL in the cells of patients at diagnosis compared to age-adjusted controls. In patients reaching CCR after chemotherapy, telomere shortening was less pronounced than in persistence or relapse but still significantly shortened compared to controls. We estimate patients harboring approximately 20 years of premature telomere loss compared to healthy aged-matched subjects at the time of AML onset. Our data indicate a pre-existing telomere deficit in non-clonal hematopoiesis of AML patients providing a link between age and AML development.

  9. The control of pre-existing extensional structures on the evolution of the southern sector of the Aconcagua fold and thrust belt, southern Andes

    NASA Astrophysics Data System (ADS)

    Giambiagi, Laura B.; Alvarez, P. Pamela; Godoy, Estanislao; Ramos, Victor A.

    2003-07-01

    The Aconcagua fold and thrust belt, located in the Andean mountains at 32°30' to 34°S, has been described as a classic model of a thin-skinned thrust belt. However, new structural data from its southern sector have shown that it has a complex structural framework reflected in multiple Mesozoic extensional phases, overprinted by structural inversion, as well as thin- and thick-skinned tectonics. Two major superimposed extensional structural styles have been identified for the Mesozoic characterized by distinctly oriented stress fields. A key role in the evolution of this part of the fold and thrust belt was played by a Late Triassic to Early Jurassic depocentre and by Late Jurassic block faulting. Shortening was accommodated by a combination of inversion of pre-existing normal faults, development of footwall short cuts and both thin and thick-skinned thrusting. Synrift and postrift sedimentary rocks were uplifted by reactivation of normal faults, with further shortening along newly formed thin-skinned thrust faults. The geometry of thin-skinned fault systems is controlled by the architecture of the rift basin, competent footwalls forming barriers to the lateral propagation of detachments.

  10. Mortality patterns associated with the 1918 influenza pandemic in Mexico: evidence for a spring herald wave and lack of pre-existing immunity in older populations

    PubMed Central

    Chowell, Gerardo; Viboud, Cécile; Simonsen, Lone; Miller, Mark A.; Acuna-Soto, Rodolfo

    2010-01-01

    Background While the mortality burden of the devastating 1918 influenza pandemic has been carefully quantified in the US, Japan, and European countries, little is known about the pandemic experience elsewhere. Here, we compiled extensive archival records to quantify the pandemic mortality patterns in two Mexican cities, Mexico City and Toluca. Methods We applied seasonal excess mortality models to age-specific respiratory mortality rates for 1915–1920 and quantified the reproduction number from daily data. Results We identified 3 pandemic waves in Mexico City in spring 1918, fall 1918, and winter 1920, characterized by unusual excess mortality in 25–44 years old. Toluca experienced 2-fold higher excess mortality rates than Mexico City, but did not have a substantial 3rd wave. All age groups including those over 65 years experienced excess mortality during 1918–20. Reproduction number estimates were below 2.5 assuming a 3-day generation interval. Conclusion Mexico experienced a herald pandemic wave with elevated young adult mortality in spring 1918, similar to the US and Europe. In contrast to the US and Europe, there was no mortality sparing in Mexican seniors, highlighting potential geographical differences in pre-existing immunity to the 1918 virus. We discuss the relevance of our findings to the 2009 pandemic mortality patterns. PMID:20594109

  11. Pre-Existing Cross-Reactive Antibodies to Avian Influenza H5N1 and 2009 Pandemic H1N1 in US Military Personnel

    PubMed Central

    Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Michel; Mason, Carl J.; Walsh, Douglas S.; Saunders, David L.

    2014-01-01

    We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity. PMID:24277784

  12. Pre-existing cross-reactive antibodies to avian influenza H5N1 and 2009 pandemic H1N1 in US military personnel.

    PubMed

    Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-Ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Michel; Mason, Carl J; Walsh, Douglas S; Saunders, David L

    2014-01-01

    We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity.

  13. Lack of variant specific CD8+ T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C

    PubMed Central

    2013-01-01

    Background CTL escape mutations have been described during acute hepatitis C in patients who developed chronic disease later on. Our aim was to investigate the mutual relationship between HCV specific CD8+ T cells and evolution of the viral sequence during early acute HCV infection. Results We sequenced multiple clones of NS3 1406 epitope in 4 HLA-A*02 patients with acute hepatitis C genotype 1b infection. Pentamers specific for the variants were used to monitor the corresponding CD8+ T cell response. We observed outgrowth of mutations, which induced only a weak and thus potentially insufficient CD8+ T cell response. In one patient we observed outgrowth of variant epitopes with similarities to a different genotype rather than de novo mutations most probably due to a lack of responsiveness to these likely pre-existing variants. We could show that in acute hepatitis C CTL escape mutations occur much earlier than demonstrated in previous studies. Conclusions The adaption of the virus to a new host is characterized by a high and rapid variability in epitopes under CD8+ T cell immune pressure. This adaption takes place during the very early phase of acute infection and strikingly some sequences were reduced below the limit of detection at some time points but were detected at high frequency again at later time points. Independent of the observed variability, HCV-specific CD8+ T cell responses decline and no adaption to different or new antigens during the course of infection could be detected. PMID:24073713

  14. Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3

    PubMed Central

    Maekawa, Tomoki; Briones, Ruel A.; Resuello, Ranillo R.G.; Tuplano, Joel V.; Hajishengallis, Evlambia; Kajikawa, Tetsuhiro; Koutsogiannaki, Sophia; Garcia, Cristina A.G.; Ricklin, Daniel; Lambris, John D.; Hajishengallis, George

    2016-01-01

    Aim Human periodontitis is associated with overactivation of complement, which is triggered by different mechanisms converging on C3, the central hub of the system. We assessed whether the C3 inhibitor Cp40 inhibits naturally-occurring periodontitis in non-human primates. Materials and Methods Non-human primates with chronic periodontitis were intra-gingivally injected with Cp40 either once (5 animals) or three times (10 animals) weekly for six weeks followed by a 6-week follow-up period. Clinical periodontal examinations and collection of gingival crevicular fluid and biopsies of gingiva and bone were performed at baseline and during the study. A one-way repeated measures ANOVA was used for data analysis. Results Whether administered once or three times weekly, Cp40 caused a significant reduction in clinical indices that measure periodontal inflammation (gingival index and bleeding on probing), tissue destruction (probing pocket depth and clinical attachment level) or tooth mobility. These clinical changes were associated with significantly reduced levels of pro-inflammatory mediators and decreased numbers of osteoclasts in bone biopsies. The protective effects of Cp40 persisted, albeit at reduced efficacy, for at least six weeks following drug discontinuation. Conclusion Cp40 inhibits pre-existing chronic periodontal inflammation and osteoclastogenesis in non-human primates, suggesting a novel adjunctive anti-inflammatory therapy for treating human periodontitis. PMID:26728318

  15. Immunogenicity and Safety of Trivalent Split Influenza Vaccine in Healthy Korean Adults with Low Pre-Existing Antibody Levels: An Open Phase I Trial

    PubMed Central

    Kang, Kyuri; Han, Seunghoon; Hong, Taegon; Jeon, Sangil; Paek, Jeongki; Kang, Jin Han

    2016-01-01

    Purpose A phase I clinical trial was conducted to evaluate the immunogenicity and safety of newly developed egg-cultivated trivalent inactivated split influenza vaccine (TIV) in Korea. Materials and Methods The TIV was administered to 43 healthy male adults. Subjects with high pre-existing titers were excluded in a screening step. Immune response was measured by a hemagglutination inhibition (HI) assay. Results The seroprotection rates against A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2009 were 74.42% [95% confidence interval (CI): 61.38–87.46], 72.09% (95% CI: 58.69–85.50), and 86.05% (95% CI: 75.69–96.40), respectively. Calculated seroconversion rates were 74.42% (95% CI: 61.38–87.46), 74.42% (95% CI: 61.38–87.46), and 79.07% (95% CI: 66.91–91.23), respectively. There were 25 episodes of solicited local adverse events in 21 subjects (47.73%), 21 episodes of solicited general adverse events in 16 subjects (36.36%) and 5 episodes of unsolicited adverse events in 5 subjects (11.36%). All adverse events were grade 1 or 2 and disappeared within three days. Conclusion The immunogenicity and safety of TIV established in this phase I trial are sufficient to plan a larger scale clinical trial. PMID:27593862

  16. Long term health-related quality of life after burns is strongly dependent on pre-existing disease and psychosocial issues and less due to the burn itself.

    PubMed

    Orwelius, L; Willebrand, M; Gerdin, B; Ekselius, L; Fredrikson, M; Sjöberg, F

    2013-03-01

    Health-related quality of life (HRQoL) is reduced after a burn, and is affected by coexisting conditions. The aims of the investigation were to examine and describe effects of coexisting disease on HRQoL, and to quantify the proportion of burned people whose HRQoL was below that of a reference group matched for age, gender, and coexisting conditions. A nationwide study covering 9 years and examined HRQoL 12 and 24 months after the burn with the SF-36 questionnaire. The reference group was from the referral area of one of the hospitals. The HRQoL of the burned patients was below that of the reference group mainly in the mental dimensions, and only single patients were affected in the physical dimensions. The factor that significantly affected most HRQoL dimensions (n=6) after the burn was unemployment, whereas only smaller effects could be attributed directly to the burn. Poor HRQoL was recorded for only a small number of patients, and the decline were mostly in the mental dimensions when compared with a group adjusted for age, gender, and coexisting conditions. Factors other than the burn itself, such as mainly unemployment and pre-existing disease, were most important for the long term HRQoL experience in these patients. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  17. Pre-existence and Persistence of Resistant Minority Hepatitis C Virus Variants in Genotype 1-Infected Patients Treated With Simeprevir/Peginterferon/Ribavirin.

    PubMed

    Fevery, Bart; Thys, Kim; Van Eygen, Veerle; Verbinnen, Thierry; Van Rossem, Elizabeth; Buelens, Annemie; Aerssens, Jeroen; Witek, James; Picchio, Gaston; De Meyer, Sandra; Lenz, Oliver

    2016-03-01

    Background.  The pre-existence of minority hepatitis C virus (HCV) variants and their impact on treatment outcome, as well as the persistence of emerging resistant variants posttreatment in patients failing treatment with simeprevir/peginterferon/ribavirin (SMV/PR), were assessed by deep sequencing (DS). Methods.  Population sequencing (PS) and Illumina DS were performed on HCV genotype 1 isolates from patients treated with SMV/PR in Phase 2b (PILLAR [NCT00882908] and ASPIRE [NCT00980330]) and Phase 3 (QUEST-1 [NCT01289782], QUEST-2 [NCT01290679], and PROMISE [NCT01281839]) trials. Results.  Minority polymorphisms (ie, detected pretreatment by DS only) reducing SMV activity in vitro were uncommon (3.6%, 19 of 534 patients). These SMV-resistant minority polymorphisms were detected in similar proportions of patients achieving (3.7%) and not achieving (3.3%) sustained virologic response with SMV/PR and generally did not emerge as major variants at time of failure. SMV-resistant variants emerging at time of failure were no longer detected at end of study in 69.3% and 52.0% of the patients by PS and DS, respectively. Conclusions.  Minority polymorphisms did not impact outcome of SMV/PR treatment. The majority of emerging variants that became undetectable at end of study by PS were also undetectable by DS. These results suggest no added value of DS for clinical usage of SMV.

  18. An XML model of an enhanced data dictionary to facilitate the exchange of pre-existing clinical research data in international studies.

    PubMed

    Duda, Stephany N; Cushman, Clint; Masys, Daniel R

    2007-01-01

    Pre-existing clinical research data sets exchanged in international epidemiology research often lack the elements needed to assess their suitability for use in multi-region meta-analyses or other clinical studies. While the missing information is generally known to local investigators, it is not contained in the files exchanged between sites. Instead, such content must be solicited by the study coordinating center though a series of lengthy phone and electronic communications: an informal process whose reproducibility and accuracy decays over time. This report describes a set of supplemental information needed to assess whether clinical research data from diverse research sites are truly comparable, and what metadata ("data about the data") should be preserved when a data set is archived for future use. We propose a structured Extensible Markup Language (XML) model that captures this information. The authors hope this model will be a first step towards preserving the metadata associated with clinical research data sets, thereby improving the quality of international data exchange, data archiving, and merged-data research using data collected in many different countries, languages and care settings.

  19. An Analytical Model for Assessing Stability of Pre-Existing Faults in Caprock Caused by Fluid Injection and Extraction in a Reservoir

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Bai, Bing; Li, Xiaochun; Liu, Mingze; Wu, Haiqing; Hu, Shaobin

    2016-07-01

    Induced seismicity and fault reactivation associated with fluid injection and depletion were reported in hydrocarbon, geothermal, and waste fluid injection fields worldwide. Here, we establish an analytical model to assess fault reactivation surrounding a reservoir during fluid injection and extraction that considers the stress concentrations at the fault tips and the effects of fault length. In this model, induced stress analysis in a full-space under the plane strain condition is implemented based on Eshelby's theory of inclusions in terms of a homogeneous, isotropic, and poroelastic medium. The stress intensity factor concept in linear elastic fracture mechanics is adopted as an instability criterion for pre-existing faults in surrounding rocks. To characterize the fault reactivation caused by fluid injection and extraction, we define a new index, the "fault reactivation factor" η, which can be interpreted as an index of fault stability in response to fluid pressure changes per unit within a reservoir resulting from injection or extraction. The critical fluid pressure change within a reservoir is also determined by the superposition principle using the in situ stress surrounding a fault. Our parameter sensitivity analyses show that the fault reactivation tendency is strongly sensitive to fault location, fault length, fault dip angle, and Poisson's ratio of the surrounding rock. Our case study demonstrates that the proposed model focuses on the mechanical behavior of the whole fault, unlike the conventional methodologies. The proposed method can be applied to engineering cases related to injection and depletion within a reservoir owing to its efficient computational codes implementation.

  20. A Critical Shock Mach Number for Particle Acceleration in the Absence of Pre-existing Cosmic Rays: M=\\sqrt{5}

    NASA Astrophysics Data System (ADS)

    Vink, Jacco; Yamazaki, Ryo

    2014-01-01

    It is shown that, under some generic assumptions, shocks cannot accelerate particles unless the overall shock Mach number exceeds a critical value M\\gt\\sqrt{5}. The reason is that for M\\le \\sqrt{5} the work done to compress the flow in a particle precursor requires more enthalpy flux than the system can sustain. This lower limit applies to situations without significant magnetic field pressure. In case that the magnetic field pressure dominates the pressure in the unshocked medium, i.e., for low plasma beta, the resistivity of the magnetic field makes it even more difficult to fulfill the energetic requirements for the formation of shock with an accelerated particle precursor and associated compression of the upstream plasma. We illustrate the effects of magnetic fields for the extreme situation of a purely perpendicular magnetic field configuration with plasma beta β = 0, which gives a minimum Mach number of M = 5/2. The situation becomes more complex, if we incorporate the effects of pre-existing cosmic rays, indicating that the additional degree of freedom allows for less strict Mach number limits on acceleration. We discuss the implications of this result for low Mach number shock acceleration as found in solar system shocks, and shocks in clusters of galaxies.

  1. Effects of blending of desalinated and conventionally treated surface water on iron corrosion and its release from corroding surfaces and pre-existing scales.

    PubMed

    Liu, Haizhou; Schonberger, Kenneth D; Peng, Ching-Yu; Ferguson, John F; Desormeaux, Erik; Meyerhofer, Paul; Luckenbach, Heidi; Korshin, Gregory V

    2013-07-01

    This study examined effects of blending desalinated water with conventionally treated surface water on iron corrosion and release from corroding metal surfaces and pre-existing scales exposed to waters having varying fractions of desalinated water, alkalinities, pH values and orthophosphate levels. The presence of desalinated water resulted in markedly decreased 0.45 μm-filtered soluble iron concentrations. However, higher fractions of desalinated water in the blends were also associated with more fragile corroding surfaces, lower retention of iron oxidation products and release of larger iron particles in the bulk water. SEM, XRD and XANES data showed that in surface water, a dense layer of amorphous ferrihydrite phase predominated in the corrosion products. More crystalline surface phases developed in the presence of desalinated water. These solid phases transformed from goethite to lepidocrocite with increased fraction of desalinated water. These effects are likely to result from a combination of chemical parameters, notably variations of the concentrations of natural organic matter, calcium, chloride and sulfate when desalinated and conventionally treated waters are blended.

  2. Risk factors associated with the antimicrobial resistance of staphylococci in canine pyoderma.

    PubMed

    Huerta, Belén; Maldonado, Alfonso; Ginel, Pedro J; Tarradas, Carmen; Gómez-Gascón, Lidia; Astorga, Rafael J; Luque, Inmaculada

    2011-06-02

    This study reports the susceptibility to antimicrobial agents of staphylococci (n=105) isolated from dogs, and the factors associated with this resistance. The study animals were 23 healthy dogs (group A), 24 with first-time pyoderma (group B), and 27 with recurrent pyoderma that had undergone long-term antibiotic treatment (group C). Staphylococci were more commonly isolated from the pyoderma-affected than the healthy dogs (p<0.0001). Some 78% of the isolates were resistant to at least one antimicrobial agent. Resistance to amoxicillin-clavulanate, cephalosporins (OR 4.29, 95% CI [1.15, 16.3] respectively), enrofloxacin (OR 9.47, 95% CI [1.53, 58.5]) and ciprofloxacin (OR 79.7 95% CI [3.26, 1947.4]) was more common among group C isolates. Some 32% of all the isolates were multiresistant (MR) and 10.4% were methicillin-resistant (MRS). The probability of isolating MRS staphylococci in group C increased by a factor of four (95% CI [1.18, 17.9]) compared to A plus B. Multi-resistant (MR) isolates were obtained more commonly from urban than rural dogs (OR 3.79, 95% CI [1.09, 13.17]). All the MRS staphylococci encountered were obtained from urban dogs and more commonly from male dogs (p=0.07). This study shows that dogs bred in urban habitat, with a history of antibiotic therapy in the past year represents significant risk of being carriers of isolates resistant to methicillin (MRS) and other antimicrobials. These factors should be considered before applying an antimicrobial treatment in veterinary clinics.

  3. [A new treatment possibility for dogs with chronic or recurrent pyoderma].

    PubMed

    van den Bogaard, A E; Maes, J H; Engels, W

    1984-12-01

    Effective treatment of chronic or recurrent pyodermas in dogs is often found to be difficult. The disease apparently results from a change in the balance between the infecting microorganism: Staphylococcus aureus, and the host. This change in the normal equilibrium could be due to enhanced virulence of the infecting strain of staphylococci, but is more likely to have been caused by host factors such as disturbed non-specific defence mechanisms (of the skin) or malfunction of the immune response, e.g. hypersensitivity. When conventional forms of treatment such as grooming, skin-hygienic measures and antibiotics fail or relapses occur, immunotherapy with a staphylococcal vaccine or toxoid might be considered. In studies with experimental animals it was shown alpha-toxoid was superior to other staphylococcal toxoids or vaccines in preventing skin lesions. Four dogs with deep-seated chronic pyodermas were treated with staphylococcal alpha-toxoid emulsified in Freund's adjuvant. Three of these animals recovered, but because of severe unwanted side-effects, this form of therapy was abandoned. Ten dogs with deep-seated chronic primary pyodermas were treated with a commercially available alpha- and beta-toxoid preparation (Isopyos). Nine of these patients recovered. In two cases, however, relapses occurred several months later, but the symptoms disappeared again after a booster injection. One dog did not respond; its condition deteriorated and it had to be euthanised. As the dogs received toxoid intracutaneously as well as intramuscularly, the positive effect might be due to desensitization of the animals rather than to immunisation.

  4. The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis

    PubMed Central

    Zhang, Bin; Liang, Long; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

    2015-01-01

    Objective The aim of this meta-analysis was to explore the efficacy of sodium bicarbonate in preventing contrast-induced nephropathy (CIN). Methods We searched PubMed, Medline and the Cochrane Library from 1 January 2004 to 1 August 2014. The effect estimate was expressed as a pooled OR with 95% CI, using the fixed-effects or random-effects model. Results 20 randomised controlled trials (n=4280) were identified. Hydration with sodium bicarbonate was associated with a significant decrease in CIN among patients with pre-existing renal insufficiency (OR 0.67, 95% CI 0.47 to 0.96; p=0.027). However, moderate heterogeneity was noted across trials (I2=48%; p=0.008). Subgroup analyses indicated a better effect of sodium bicarbonate in studies using low-osmolar (OR 0.59, 95% CI 0.37 to 0.93; p=0.024) compared with iso-osmolar contrast agents (OR 0.76, 95% CI 0.43 to 1.34; p=0.351). The odds of CIN with sodium bicarbonate were lower in studies including only patients undergoing emergency (OR 0.16, 95% CI 0.05 to 0.51; p=0.002) compared with elective procedures (OR 0.76, 95% CI 0.54 to 1.06; p=0.105). Sodium bicarbonate was more beneficial in patients given a bolus injection before procedures (OR 0.15, 95% CI 0.04 to 0.54; p=0.004) compared with continuous infusion (OR 0.75, 95% CI 0.53 to 1.05; p=0.091). Sodium bicarbonate plus N-acetylcysteine (OR 0.17, 95% CI 0.04 to 0.79; p=0.024) was better than sodium bicarbonate alone (OR 0.71, 95% CI 0.48 to 1.03; p=0.071). The effect of sodium bicarbonate was considered greater in papers published before (OR 0.19, 95% CI 0.09 to 0.41; p=0.000) compared with after 2008 (OR 0.85, 95% CI 0.62 to 1.16; p=0.302). However, no significant differences were found in mortality (OR 0.69, 95% CI 0.36 to 1.32; p=0.263) or requirement for dialysis (OR 1.08, 95% CI 0.52 to 2.25; p=0.841). Conclusions Sodium bicarbonate is effective in preventing CIN among patients with pre-existing renal insufficiency. However, it fails to lower the risks of

  5. Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections.

    PubMed

    Guidry, Jacqueline A; Downing, Christopher; Tyring, Stephen K

    2015-07-01

    Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Fruit consumption and physical activity in relation to all-cause and cardiovascular mortality among 70,000 Chinese adults with pre-existing vascular disease.

    PubMed

    Tian, Xiaocao; Du, Huaidong; Li, Liming; Bennett, Derrick; Gao, Ruqin; Li, Shanpeng; Wang, Shaojie; Guo, Yu; Bian, Zheng; Yang, Ling; Chen, Yiping; Chen, Junshi; Gao, Yan; Weng, Min; Pang, Zengchang; Jiang, Baofa; Chen, Zhengming

    2017-01-01

    To assess the associations of fresh fruit consumption and total physical activity with all-cause and cardiovascular mortality among Chinese adults who have been diagnosed with cardiovascular disease (CVD) or hypertension. During 2004-08, the China Kadoorie Biobank study recruited 70,047 adults, aged 30-79 years, with physician-diagnosed stroke or transient ischaemic attack, ischemic heart disease, or hypertension. Information on diet and physical activity was collected using an interviewer-administered electronic questionnaire. Cox regression was used to yield hazard ratios (HRs) for the independent and joint associations of fresh fruit consumption and total physical activity with mortality. At baseline, 32.9% of participants consumed fresh fruit regularly (i.e. >3 days/week) and the mean total physical activity were 15.8 (SD = 11.8) MET-hr/day. During ~7-years follow-up, 6569 deaths occurred with 3563 from CVD. Compared to participants with <1 day/week fruit consumption, regular consumers had HR (95% CI) of 0.84 (0.79-0.89) for all-cause mortality and 0.79 (0.73-0.86) for CVD mortality. The HRs for the top vs bottom tertile of physical activity were 0.68 (0.64-0.72) and 0.65 (0.60-0.71), respectively, with no clear evidence of reverse causality. After correcting for regression dilution, each 100 g/day usual consumption of fresh fruit or 10 MET-hr/day usual levels of physical activity was associated with 23-29% lower mortality. The combination of regular fruit consumption with top 3rd of physical activity (>16.53 MET-hr/day) was associated with about 40% lower mortality. Among Chinese adults with pre-existing vascular disease, higher physical activity and fruit consumption were both independently and jointly associated with lower mortality.

  7. Cenozoic evolution of the Yilan-Yitong Graben in NE China: An example of graben formation controlled by pre-existing structures

    NASA Astrophysics Data System (ADS)

    Gu, Chengchuan; Zhu, Guang; Zhang, Shuai; Liu, Cheng; Li, Yunjian; Lin, Shaoze; Wang, Wei

    2017-09-01

    The NE-trending Yilan-Yitong Graben (YYG) occurs along the Yilan-Yitong Fault Zone in the northern segment of the Tan-Lu Fault Zone, northeastern China. It shows an unusually narrow, straight shape in map view with a length of ca. 600 km and width of <25 km. From northeast to southwest, the YYG is composed of the Tangyuan Graben bounded by one main fault, and the Fangzheng, Shulan, and Yitong grabens bounded by two main faults. The graben boundary faults strike NE-SW, whereas the graben interiors are dominated by E-W normal faults. The graben architectures and depocenters were controlled mainly by the NE-striking faults, but were also affected by some major E-W normal faults. Integration of our structural data with oil exploration results demonstrate four stages of Cenozoic evolution for the YYG: (1) Paleogene rifting under N-S extension; (2) compression-induced inversion at the end of the Paleogene; (3) Neogene subsidence under a weak extensional setting; and (4) Quaternary E-W compression. The NE-striking graben boundary faults behaved as normal dextral faults during the Paleogene due to oblique extension. It is proposed that the YYG formed through reactivation of the pre-existing Yilan-Yitong strike-slip fault zone under Paleogene N-S extension and that it represents an oblique extensional graben rather than an orthogonal extensional graben, a pull-apart basin, or transtensional graben as previously proposed. The narrow, straight shape of the YYG results from reactivation of the straight strike-slip fault zone under oblique extension.

  8. Fruit consumption and physical activity in relation to all-cause and cardiovascular mortality among 70,000 Chinese adults with pre-existing vascular disease

    PubMed Central

    Tian, Xiaocao; Li, Liming; Bennett, Derrick; Gao, Ruqin; Li, Shanpeng; Wang, Shaojie; Guo, Yu; Bian, Zheng; Yang, Ling; Chen, Yiping; Chen, Junshi; Gao, Yan; Weng, Min; Pang, Zengchang; Jiang, Baofa; Chen, Zhengming

    2017-01-01

    Objectives To assess the associations of fresh fruit consumption and total physical activity with all-cause and cardiovascular mortality among Chinese adults who have been diagnosed with cardiovascular disease (CVD) or hypertension. Methods During 2004–08, the China Kadoorie Biobank study recruited 70,047 adults, aged 30–79 years, with physician-diagnosed stroke or transient ischaemic attack, ischemic heart disease, or hypertension. Information on diet and physical activity was collected using an interviewer-administered electronic questionnaire. Cox regression was used to yield hazard ratios (HRs) for the independent and joint associations of fresh fruit consumption and total physical activity with mortality. Results At baseline, 32.9% of participants consumed fresh fruit regularly (i.e. >3 days/week) and the mean total physical activity were 15.8 (SD = 11.8) MET-hr/day. During ~7-years follow-up, 6569 deaths occurred with 3563 from CVD. Compared to participants with <1 day/week fruit consumption, regular consumers had HR (95% CI) of 0.84 (0.79–0.89) for all-cause mortality and 0.79 (0.73–0.86) for CVD mortality. The HRs for the top vs bottom tertile of physical activity were 0.68 (0.64–0.72) and 0.65 (0.60–0.71), respectively, with no clear evidence of reverse causality. After correcting for regression dilution, each 100 g/day usual consumption of fresh fruit or 10 MET-hr/day usual levels of physical activity was associated with 23–29% lower mortality. The combination of regular fruit consumption with top 3rd of physical activity (>16.53 MET-hr/day) was associated with about 40% lower mortality. Conclusion Among Chinese adults with pre-existing vascular disease, higher physical activity and fruit consumption were both independently and jointly associated with lower mortality. PMID:28403155

  9. Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques

    PubMed Central

    Jaworski, Juan Pablo; Bryk, Peter; Brower, Zachary; Zheng, Bo; Hessell, Ann J.; Rosenberg, Alexander F.; Wu, Tong Tong; Sanz, Ignacio; Keefer, Michael C.; Haigwood, Nancy L.

    2017-01-01

    Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig) purified from previously infected animals (SHIVIG) or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2–3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host’s ability to eliminate HIV. PMID:28222180

  10. Impact of Pre-Existing Elastic Matrix on TGF-β1 and HA Oligomer-Induced Regenerative Repair by Rat Aortic Smooth Muscle Cells

    PubMed Central

    Gacchina, Carmen E.; Ramamurthi, Anand

    2010-01-01

    Regenerating elastic matrices lost to disease (e.g. in aneurysms) is vital to re-establishing vascular homeostasis but is challenged by poor elastogenicity of post-neonatal cells. We previously showed exogenous hyaluronan oligomers (HA-o) and TGF-β1 to synergistically enhance tropo and matrix elastin deposition by healthy adult rat aortic SMCs (RASMCs). Towards treating aortic aneurysms (AAs), which exhibit cause- and site-specific heterogeneity in matrix content/structure and contain proteolytically-injured SMCs, we investigated impact of pre-existing elastic matrix degeneration on elastogenic induction of injured RASMCs. Elastin-rich RASMC layers at 21 days of culture, were treated with 0.15 U/ml (PPE15) and 0.75 U/ml (PPE75) of porcine pancreatic elastase to degrade the elastic matrix variably, or left uninjured (control). One set of cultures was harvested at 21d, before and after injury, to quantify viable cell count, matrix elastin loss. Other injured cell layers were cultured to 42d with or without factors (0.2 μg/ml HA oligomers, 1 ng/ml TGF-β1). We showed that (a)ability of cultures to self-repair and regenerate elastic matrices following proteolysis is limited when elastolysis is severe, (b)HA oligomers and TGF-β1 elastogenically stimulate RASMCs in mildly-injured (i.e., PPE15) cultures to restore both elastic matrix amounts and elastic-fiber deposition to levels in healthy cultures, and (c) in severely injured (i.e., PPE75) cultures, the factors stimulate matrix elastin synthesis and crosslinking, though not to control levels. The outcomes underscore need to enhance elastogenic factor doses based on severity of elastin loss. This study will help customize therapies for elastin regeneration within AAs based on cause and location. PMID:20653044

  11. The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry.

    PubMed

    Oliva, Karen; Barker, Gillian; Riley, Clyde; Bailey, Mark J; Permezel, Michael; Rice, Gregory E; Lappas, Martha

    2012-04-01

    Our aim was to study the protein expression profiles of placenta obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section. We used two-dimensional difference gel electrophoresis (2D-DIGE), utilising narrow-range immobilised pH gradient strips that encompassed the broad pH range of 4-5 and 5-6, followed by MALDI-TOF mass spectrometry of selected protein spots. Western blot and quantitative RT-PCR (qRT-PCR) analyses were performed to validate representative findings from the 2D-DIGE analysis. Eight proteins were altered (six down-regulated and two up-regulated on obese placentas). Annexin A5 (ANXA5), ATP synthase subunit beta, mitochondria (ATPB), brain acid soluble protein 1 (BASP1), ferritin light chain (FTL), heterogeneous nuclear ribonucleoprotein C (HNRPC) and vimentin (VIME) were all lower in obese patients. Alpha-1-antitrypsin (A1AT) and stress-70 protein, mitochondrial (GRP75) were higher in obese patients. Western blot analysis of ANXA5, ATPB, FTL, VIME, A1AT and GRP75 confirmed the findings from the 2D-DIGE analysis. For brain acid soluble protein 1 and HNRPC, qRT-PCR analysis also confirmed the findings from the 2D-DIGE analysis. Immunohistochemical analysis was also used to determine the localisation of the proteins in human placenta. In conclusion, proteomic analysis of placenta reveals differential expression of several proteins in patients with pre-existing obesity. These proteins are implicated in a variety of cellular functions such as regulation of growth, cytoskeletal structure, oxidative stress, inflammation, coagulation and apoptosis. These disturbances may have significant implications for fetal growth and development.

  12. Mechanical Behavior of Brittle Rock-Like Specimens with Pre-existing Fissures Under Uniaxial Loading: Experimental Studies and Particle Mechanics Approach

    NASA Astrophysics Data System (ADS)

    Cao, Ri-hong; Cao, Ping; Lin, Hang; Pu, Cheng-zhi; Ou, Ke

    2016-03-01

    Joints and fissures with similar orientation or characteristics are common in natural rocks; the inclination and density of the fissures affect the mechanical properties and failure mechanism of the rock mass. However, the strength, crack coalescence pattern, and failure mode of rock specimens containing multi-fissures have not been studied comprehensively. In this paper, combining similar material testing and discrete element numerical method (PFC2D), the peak strength and failure characteristics of rock-like materials with multi-fissures are explored. Rock-like specimens were made of cement and sand and pre-existing fissures created by inserting steel shims into cement mortar paste and removing them during curing. The peak strength of multi-fissure specimens depends on the fissure angle α (which is measured counterclockwise from horizontal) and fissure number ( N f). Under uniaxial compressional loading, the peak strength increased with increasing α. The material strength was lowest for α = 25°, and highest for α = 90°. The influence of N f on the peak strength depended on α. For α = 25° and 45°, N f had a strong effect on the peak strength, while for higher α values, especially for the 90° sample, there were no obvious changes in peak strength with different N f. Under uniaxial compression, the coalescence modes between the fissures can be classified into three categories: S-mode, T-mode, and M-mode. Moreover, the failure mode can be classified into four categories: mixed failure, shear failure, stepped path failure, and intact failure. The failure mode of the specimen depends on α and N f. The peak strength and failure modes in the numerically simulated and experimental results are in good agreement.

  13. Modeling Aseismic and Seismic Slip Induced by Fluid Injection on Pre-existing Faults Governed by Rate-and-state Friction

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Harrington, R. M.; Deng, K.; Larochelle, S.

    2015-12-01

    Pore fluid pressure evolution on pre-existing faults in the vicinity of fluid injection activity has been postulated as a key factor for inducing both moderate size earthquakes and aseismic slip. In this study, we develop a numerical model incorporating rate-and-state friction properties to investigate fault slip initiated by various perturbations, including fluid injection and transient dynamic stress changes. In the framework of rate-and-state friction, external stress perturbations and their spatiotemporal variation can be coupled to fault frictional strength evolution in a single computational procedure. Hence it provides a quantitative understanding of the source processes (i.e., slip rate, rupture area, triggering threshold) of a spectrum of slip modes under the influence of anthropogenic and natural perturbations. Preliminary results show both the peak and cumulative Coulomb stress change values can affect the transition from aseismic to seismic slip and the amount of slip. We plan to apply the physics-based slip model to induced earthquakes in western Canada sedimentary basins. In particular, we will focus on the Fox Creek sequences in north Alberta, where two earthquakes of ML4.4 (2015/01/23) and Mw4.6 (2015/06/13) were potentially induced by nearby hydraulic fracturing activity. The geometry of the seismogenic faults of the two events will be constrained by relocated seismicity as well as their focal mechanism solutions. Rate-and-state friction parameters and ambient stress conditions will be constrained by identifying dynamic triggering criteria using a matched-filter approach. A poroelastic model will be used to estimate the pore pressure history resolved onto the fault plane due to fluid injection. By comparing modeled earthquake source parameters to those estimated from seismic analysis, we aim to quantitatively discern the nucleation conditions of injection-induced versus dynamically triggered earthquakes, and aseismic versus seismic slip modes.

  14. Association between intraoperative ventilator settings and plasma levels of soluble receptor for advanced glycation end-products in patients without pre-existing lung injury.

    PubMed

    Jabaudon, Matthieu; Futier, Emmanuel; Roszyk, Laurence; Sapin, Vincent; Pereira, Bruno; Constantin, Jean-Michel

    2015-10-01

    The soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated and correlated with severity in patients with acute respiratory distress syndrome (ARDS). The impact of ventilator settings on plasma levels of sRAGE, in patients with or without pre-existing lung injury, remains under-investigated to date. Our objective was to assess the effects of a lung-protective ventilation strategy (combining low tidal volume, positive end-expiratory pressure and recruitment maneuvers), as compared with a non-protective approach (with high tidal volume and zero end-expiratory pressure), on plasma levels of sRAGE in patients without lung injury undergoing major abdominal surgery. Plasma samples were obtained from 95 patients enrolled in a large randomized controlled trial of lung-protective ventilation for major abdominal surgery. Plasma levels of sRAGE were measured in duplicate with an enzyme-linked immunoassay on day 1, immediately after surgery, and on postoperative days 1, 3 and 7. Early postoperative plasma levels of sRAGE were significantly lower in the lung-protective ventilation group (n = 47) than in the non-protective ventilation group (n = 48) (mean (standard deviation), 1782 (836) vs 2171 (1678) pg/mL, respectively, P = 0.03). Intraoperative changes in plasma sRAGE were associated with postoperative hypoxemia and ARDS. A lung-protective ventilation strategy decreased plasma sRAGE in patients without lung injury undergoing major abdominal surgery compared with the patients with non-protective ventilation. This intraoperative decrease could reflect a lesser degree of epithelial injury. © 2015 Asian Pacific Society of Respirology.

  15. A Rapid-Response Humoral Vaccine Platform Exploiting Pre-Existing Non-Cognate Populations of Anti-Vaccine or Anti-Viral CD4+ T Helper Cells to Confirm B Cell Activation

    PubMed Central

    Hills, Thomas; Jakeman, Phillip G.; Carlisle, Robert C.; Klenerman, Paul; Seymour, Leonard W.; Cawood, Ryan

    2016-01-01

    The need for CD4+ T cell responses to arise de novo following vaccination can limit the speed of B cell responses. Populations of pre-existing vaccine-induced or anti-viral CD4+ T cells recognising distinct antigens could be exploited to overcome this limitation. We hypothesise that liposomal vaccine particles encapsulating epitopes that are recognised, after processing and B cell MHCII presentation, by pre-existing CD4+ T cells will exploit this pre-existing T cell help and result in improved antibody responses to distinct target antigens displayed on the particle surface. Liposomal vaccine particles were engineered to display the malaria circumsporozoite (CSP) antigen on their surface, with helper CD4+ epitopes from distinct vaccine or viral antigens contained within the particle core, ensuring the B cell response is raised but focused against CSP. In vivo vaccination studies were then conducted in C57Bl/6 mice as models of either vaccine-induced pre-existing CD4+ T cell immunity (using ovalbumin—OVA) or virus-induced pre-existing CD4+ T cell immunity (murine cytomegalovirus—MCMV). Following the establishment of pre-existing by vaccination (OVA in the adjuvant TiterMax® Gold) or infection with MCMV, mice were administered CSP-coated liposomal vaccines containing the relevant OVA or MCMV core CD4+ T cell epitopes. In mice with pre-existing anti-OVA CD4+ T cell immunity, these vaccine particles elicited rapid, high-titre, isotype-switched CSP-specific antibody responses—consistent with the involvement of anti-OVA T helper cells in confirming activation of anti-CSP B cells. Responses were further improved by entrapping TLR9 agonists, combining humoral vaccination signals ‘one’, ‘two’ and ‘three’ within one particle. Herpes viruses can establish chronic infection and elicit significant, persistent cellular immune responses. We then demonstrate that this principle can be extended to re-purpose pre-existing anti-MCMV immunity to enhance anti

  16. Comparison of a chlorhexidine and a benzoyl peroxide shampoo as sole treatment in canine superficial pyoderma.

    PubMed

    Loeffler, A; Cobb, M A; Bond, R

    2011-09-03

    The clinical and antibacterial efficacy of two shampoos used as a sole antibacterial treatment in dogs with superficial pyoderma were investigated and compared. In a randomised, partially blinded study, a 3 per cent chlorhexidine gluconate shampoo (Chlorhex 3; Leo Animal Health) was compared against a 2.5 per cent benzoyl peroxide shampoo (Paxcutol; Virbac) in 22 dogs with superficial pyoderma. Dogs were washed two to three times weekly with a 10-minute contact time over 21 days. Clinical scores and bacterial counts were assessed on days 1, 8 and 22 and compared within and between treatment groups; overall response was assessed at the end of the study. Twenty dogs completed the study; 15 (68.2 per cent) showed an overall clinical improvement and the clinical signs resolved in three chlorhexidine-treated dogs. In the chlorhexidine-treated group, scores for papules/pustules (P<0.001), investigator-assessed pruritus (P=0.003), total bacterial counts (P=0.003) and counts for coagulase-positive staphylococci (P=0.003) were reduced after three weeks. Scores and bacterial counts did not vary significantly in the benzoyl peroxide-treated group.

  17. Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study.

    PubMed

    Bell, R; Glinianaia, S V; Tennant, P W G; Bilous, R W; Rankin, J

    2012-02-08

    AIMS: The aim of this study was to quantify the risk of major congenital anomaly, and to assess the influence of peri-conception HbA(1c) and other clinical and socio-demographic factors on the risk of congenital anomaly occurrence in offspring of women with type 1 and type 2 diabetes diagnosed before pregnancy. METHODS: This was a population-based cohort study using linked data from registers of congenital anomaly and diabetes in pregnancy. A total of 401,149 singleton pregnancies (1,677 in women with diabetes) between 1996 and 2008 resulting in live birth, fetal death at ≥20 weeks' gestation or termination of pregnancy for fetal anomaly were included. RESULTS: The rate of non-chromosomal major congenital anomaly in women with diabetes was 71.6 per 1,000 pregnancies (95% CI 59.6, 84.9), a relative risk of 3.8 (95% CI 3.2, 4.5) compared with women without diabetes. There was a three- to sixfold increased risk across all common anomaly groups. In a multivariate analysis, peri-conception glycaemic control (adjusted OR [aOR] 1.3 [95% CI 1.2, 1.4] per 1% [11 mmol/mol] linear increase in HbA(1c) above 6.3% [45 mmol/mol]) and pre-existing nephropathy (aOR 2.5 [95% CI 1.1, 5.3]) were significant independent predictors of congenital anomaly. Associations with gestation at booking (aOR 1.1 [95% CI 1.0, 1.1]) and parity (aOR 1.6 [95% CI 1.0, 2. 5]) were not significant. Unadjusted risk was higher for women from deprived areas or who did not take folate. Type and duration of diabetes, ethnicity, age, BMI, preconception care, smoking and fetal sex were not associated with congenital anomaly risk. CONCLUSIONS: Peri-conception glycaemia is the most important modifiable risk factor for congenital anomaly in women with diabetes. The association with nephropathy merits further study.

  18. Photosynthetic traits around budbreak in pre-existing needles of Sakhalin spruce (Picea glehnii) seedlings grown under elevated CO2 concentration assessed by chlorophyll fluorescence measurements.

    PubMed

    Kitao, Mitsutoshi; Tobita, Hiroyuki; Utsugi, Hajime; Komatsu, Masabumi; Kitaoka, Satoshi; Maruyama, Yutaka; Koike, Takayoshi

    2012-08-01

    To assess the effects of elevated CO(2) concentration ([CO(2)]) on the photosynthetic properties around spring budbreak, we monitored the total leaf sugar and starch content, and chlorophyll fluorescence in 1-year-old needles of Sakhalin spruce (Picea glehnii Masters) seedlings in relation to the timing of budbreak, grown in a phytotron under natural daylight at two [CO(2)] levels (ambient: 360 μmol mol(-1) and elevated: 720 μmol mol(-1)). Budbreak was accelerated by elevated [CO(2)] accompanied with earlier temporal declines in the quantum yield of PSII electron transport (Φ(PSII)) and photochemical quenching (q(L)). Plants grown under elevated [CO(2)] showed pre-budbreak leaf starch content twice as high with no significant difference in Φ(PSII) from ambient-CO(2)-grown plants when compared at the same measurement [CO(2)], i.e., 360 or 720 μmol mol(-1), suggesting that the enhanced pre-budbreak leaf starch accumulation might not cause down-regulation of photosynthesis in pre-existing needles under elevated [CO(2)]. Conversely, lower excitation pressure adjusted for the efficiency of PSII photochemistry ((1 - q(P)) F(v)'/F(m)') was observed in plants grown under elevated [CO(2)] around budbreak when compared at their growth [CO(2)] (i.e., comparing (1 - q(P)) F(v)'/F(m)' measured at 720 μmol mol(-1) in elevated-CO(2)-grown plants with that at 360 μmol mol(-1) in ambient-CO(2)-grown plants), which suggests lower rate of photoinactivation of PSII in the elevated-CO(2)-grown plants around spring budbreak. The degree of photoinhibition, as indicated by the overnight-dark-adapted F(v)/F(m), however, showed no difference between CO(2) treatments, thereby suggesting that photoprotection during the daytime or the repair of PSII at night was sufficient to alleviate differences in the rate of photoinactivation.

  19. Modeling fault kinematics, segment interaction and transfer zone geometry as a function of pre-existing fabrics: the Albertine rift, East African Rift System.

    NASA Astrophysics Data System (ADS)

    Aanyu, Kevin; Koehn, Daniel

    2010-05-01

    This study focuses on the development of the Rwenzori Mountains, an uplift horst block within the northern-most segment of the western branch of the East African Rift System (EARS). Attention is drawn to the role of pre-existing crustal weaknesses left behind by Proterozoic mobile belts that pass around cratonic Archean shields namely the Tanzanian Craton to the southeast and the Congo craton to the northwest. We study how the southward propagating sub-segment of the rift that contains Lake Albert to the north interacts with the northward propagating sub-segment that contains the lakes Edward and George and how this interaction produces the structural geometries observed within and around the Rwenzori horst block. Analogue experiments are used to simulate behavior of the upper crust with pre-cut rubber strips of varying overstep/overlap, placed oblique and/or orthogonal to the extension vector. The points of connection to the basal sheet present velocity discontinuities to localize deformation below the sand. Surface geometry of the developing rifts and section cuts are used to study the kinematics that result from the given boundary conditions. In general we try to model two parallel rifts that propagate towards each other and interact. Results show that greater overstep of rifts produces an oblique shear-dominated transfer zone with deep grabens (max.7.0km) in the adjoining segments. Smaller overlap ends in extension-dominated transfer, offset rift segments without oblique transfer faults to join two adjacent rift arms and produces moderately deep grabens (max.4.6km). When overlap doubles the overstep (SbR5), rifts propagate sub-orthogonal to the extension direction in a rotation-dominated transfer and form shallow valleys (max.2.9km). Whether a block like the Rwenzori Mountains is captured and rotates, depends on the overlap/overstep ratio where the rotation direction of a captured block is determined by the sense of overlap (right- or left-lateral). Fault

  20. Integrity of Pre-existing Wellbores in Geological Sequestration of CO2 – Assessment Using a Coupled Geomechanics-fluid Flow Model

    DOE PAGES

    Kelkar, Sharad; Carey, J. William; Dempsey, David; ...

    2014-12-31

    Assessment of potential CO2 and brine leakage from wellbores is central to any consideration of the viability of geological CO2 sequestration. Depleted oil and gas reservoirs are some of the potential candidates for consideration as sequestration sites. The sequestration sites are expected to cover laterally extensive areas to be of practical interest. Hence there is a high likelihood that such sites will contain many pre-existing abandoned wells. Most existing work on wellbore integrity has focused on field and laboratory studies of chemical reactivity. Very little work has been done on the impacts of mechanical stresses on wellbore performance. This studymore » focuses on the potential enhancement of fluid flow pathways in the near-wellbore environment due to modifications in the geomechanical stress field resulting from the CO2 injection operations. The majority of the operational scenarios for CO2 sequestration lead to significant rise in the formation pore pressure. This is expected to lead to an expansion of the reservoir rock and build-up of shear stresses near wellbores where the existence of cement and casing are expected to constrain the expansion. If the stress buildup is large enough, this can lead to failure with attendant permeability enhancement that can potentially provide leakage pathways to shallower aquifers and the surface. In this study, we use a numerical model to simulate key features of a wellbore (casing, annulus and cement) embedded in a system that includes the upper aquifer, caprock, and storage aquifer. We present the sensitivity of damage initiation and propagation to various operational and formation parameters. We consider Mohr-Coulomb shear-failure models; tensile failure is also likely to occur but will require higher stress changes and will be preceded by shear failure. The modeling is performed using the numerical simulator FEHM developed at LANL that models coupled THM processes during multi-phase fluid flow and deformation in

  1. Integrity of Pre-existing Wellbores in Geological Sequestration of CO2 – Assessment Using a Coupled Geomechanics-fluid Flow Model

    SciTech Connect

    Kelkar, Sharad; Carey, J. William; Dempsey, David; Lewis, Kayla

    2014-12-31

    Assessment of potential CO2 and brine leakage from wellbores is central to any consideration of the viability of geological CO2 sequestration. Depleted oil and gas reservoirs are some of the potential candidates for consideration as sequestration sites. The sequestration sites are expected to cover laterally extensive areas to be of practical interest. Hence there is a high likelihood that such sites will contain many pre-existing abandoned wells. Most existing work on wellbore integrity has focused on field and laboratory studies of chemical reactivity. Very little work has been done on the impacts of mechanical stresses on wellbore performance. This study focuses on the potential enhancement of fluid flow pathways in the near-wellbore environment due to modifications in the geomechanical stress field resulting from the CO2 injection operations. The majority of the operational scenarios for CO2 sequestration lead to significant rise in the formation pore pressure. This is expected to lead to an expansion of the reservoir rock and build-up of shear stresses near wellbores where the existence of cement and casing are expected to constrain the expansion. If the stress buildup is large enough, this can lead to failure with attendant permeability enhancement that can potentially provide leakage pathways to shallower aquifers and the surface. In this study, we use a numerical model to simulate key features of a wellbore (casing, annulus and cement) embedded in a system that includes the upper aquifer, caprock, and storage aquifer. We present the sensitivity of damage initiation and propagation to various operational and formation parameters. We consider Mohr-Coulomb shear-failure models; tensile failure is also likely to occur but will require higher stress changes and will be preceded by shear failure. The modeling is performed using the numerical simulator FEHM developed at LANL that models coupled THM processes during multi

  2. The use of continuous ambulatory peritoneal dialysis for patients with end-stage renal disease and pre-existing advanced liver disease.

    PubMed

    Kaul, Anupma; Sharma, R K; Gupta, Amit; Prasad, Narayan

    2013-07-01

    End-stage renal disease (ESRD) associated with pre-existing advanced liver disease (ALD) has increased the risk of morbidity and mortality. The aim of this study is to assess the outcome following the use of continuous ambulatory peritoneal dialysis (CAPD) in ESRD patients with ALD. A retrospective case-controlled study was performed on 16 patients with ALD and ESRD (ESRD-ALD) and 27 control patients with ESRD but without liver disease (ESRD); both groups were started on CAPD during the same period. No major complications were observed in either group in the immediate post-surgical period and, after an average break in period of 11.3 days, the cases and controls were started on regular CAPD. The average duration of follow-up was 8 ± 2.3 months in the ESRD-ALD group compared with 20 ± 1.3 months in the ESRD group. The overall peritonitis rates were 1.26/treatment year in the ESRD-ALD group and 0.63 in the ESRD group. The 6- and 12-month survivals among ESRD-ALD patients were 63.75% and 38.75%, respectively. Patients with ESRD-ALD had significantly lower baseline serum protein and albumin levels at the time of initiation of CAPD. On follow-up, the hemoglobin levels improved in both the groups along with an improvement in the serum protein and albumin levels. Fourteen of the 16 ESRD-ALD patients died at the end of the 3-year follow-up period; deaths were due to terminal liver failure in nine patients and peritonitis in five patients. Patients who died in the ESRD-ALD group had lower serum albumin, lower body mass index (BMI) (median BMI 18.2 vs. 25.6) and higher grades of liver disease [child Pugh grade B (8), grade C (6) vs. grade B (2)] at initiation of CAPD. Our study suggests that CAPD is a safe modality in patients with ESRD-ALD and that it does not carry any major risk for bleeding tendencies, technique failure or worsening of nutritional status. Low serum albumin, lower BMI and higher grade of liver disease at initiation are associated with higher mortality

  3. Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients

    PubMed Central

    Zhang, Yu; Cao, Ying; Zhang, Renwen; Zhang, Xiaxia; Lu, Haiying; Wu, Chihong; Huo, Na; Xu, Xiaoyuan

    2016-01-01

    Background The efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline. Methods Direct sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus. Results The incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region. Conclusions Pre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline. PMID:27812165

  4. Testing the influence of vertical, pre-existing joints on normal faulting using analogue and 3D discrete element models (DEM)

    NASA Astrophysics Data System (ADS)

    Kettermann, Michael; von Hagke, Christoph; Virgo, Simon; Urai, Janos L.

    2015-04-01

    Brittle rocks are often affected by different generations of fractures that influence each other. We study pre-existing vertical joints followed by a faulting event. Understanding the effect of these interactions on fracture/fault geometries as well as the development of dilatancy and the formation of cavities as potential fluid pathways is crucial for reservoir quality prediction and production. Our approach combines scaled analogue and numerical modeling. Using cohesive hemihydrate powder allows us to create open fractures prior to faulting. The physical models are reproduced using the ESyS-Particle discrete element Modeling Software (DEM), and different parameters are investigated. Analogue models were carried out in a manually driven deformation box (30x28x20 cm) with a 60° dipping pre-defined basement fault and 4.5 cm of displacement. To produce open joints prior to faulting, sheets of paper were mounted in the box to a depth of 5 cm at a spacing of 2.5 cm. Powder was then sieved into the box, embedding the paper almost entirely (column height of 19 cm), and the paper was removed. We tested the influence of different angles between the strike of the basement fault and the joint set (0°, 4°, 8°, 12°, 16°, 20°, and 25°). During deformation we captured structural information by time-lapse photography that allows particle imaging velocimetry analyses (PIV) to detect localized deformation at every increment of displacement. Post-mortem photogrammetry preserves the final 3-dimensional structure of the fault zone. We observe that no faults or fractures occur parallel to basement-fault strike. Secondary fractures are mostly oriented normal to primary joints. At the final stage of the experiments we analyzed semi-quantitatively the number of connected joints, number of secondary fractures, degree of segmentation (i.e. number of joints accommodating strain), damage zone width, and the map-view area fraction of open gaps. Whereas the area fraction does not change

  5. Origin of the Ciomadul Dacite, Carpathian-Pannonian Region, Eastern-Central Europe: Rejuvenation of a Pre-Existing Crystal Mush

    NASA Astrophysics Data System (ADS)

    Kiss, B.; Harangi, S.; Molnar, K.; Jankovics, E. M.; Lukacs, R.; Ntaflos, T.

    2012-12-01

    Dacitic composite volcanoes and calderas worldwide have many common specific characters. Notably, their activities are fairly unpredictable since the repose time between the active phases could be rather long, i.e. even several tens or hundreds ka. This nature might be related to the origin of such magmas. Petrological observations indicate that relatively old, cool, highly crystalline magma body (i.e., a crystal mush) could be present beneath the seemingly inactive dacitic volcanoes before reawakening. Reactivation of such locked magma chambers could occur due to the upwelling and intrusion of mafic magma and recent calculations suggest that this process takes place rather fast. Understanding the nature and time-scale of such remobilization events is crucial to explain the reason of the change in volcanic behaviour from dormant to active phase (i.e., the reawakening of the volcano). In this study, we show the role and the character of a pre-existing near-solidus granodioritic crystal mush to generate the eruptible dacitic magma in the Ciomadul volcano. The Ciomadul dacite is a crystal-rich rock with ubiquitous plagioclases and amphiboles. They form viscous lava domes and pumices generated by sub-plinian explosive eruptions. Combined, mineral-scale textural and geochemical investigations indicate a complex origin of these minerals, formed partly in a low temperature dioritic-granodioritic crystal mush body, partly in higher temperature hybrid magma. In addition, biotite, titanite, apatite, allanite, zircon, K-feldspar and quartz occur in various amounts and are interpreted also as antecrysts derived from the remobilized mushy body. High-Mg olivines and clinopyroxenes represent basaltic magma intruded into the mush. The nature of the crystal mush was closely investigated through the detailed analysis of the crystal clots found often in the Ciomadul dacites. Their texture resembles plutonic rocks, but they contain interstitial vesiculated glasses. The glass could

  6. Insertion sequence IS256 in canine pyoderma isolates of Staphylococcus pseudintermedius associated with antibiotic resistance.

    PubMed

    Casagrande Proietti, P; Bietta, A; Coletti, M; Marenzoni, M L; Scorza, A V; Passamonti, F

    2012-06-15

    Staphylococcus pseudintermedius is the most frequent staphylococcal species isolated from canine pyoderma. The control of S. pseudintermedius infection is often difficult due to the expanded antimicrobial resistance phenotypes. Antibiotic resistance in staphylococcal pathogens is often associated to mobile genetic elements such as the insertion sequence IS256 that was first described as a part of the transposon Tn4001, which confers aminoglycoside resistance in Staphylococcus aureus and in Staphylococcus epidermidis. In this study a collection of 70 S. pseudintermedius isolates from canine pyoderma was used to investigate antimicrobial susceptibility to 15 antibiotics and the presence of IS256, not revealed in S. pseudintermedius yet. Antibiotic resistance profiling demonstrated that all S. pseudintermedius isolates had a multi-drug resistance phenotype, exhibiting simultaneous resistance to at least five antibiotics; indeed methicillin resistant S. pseudintermedius isolates were simultaneously resistant to at least nine antibiotics and all were also gentamicin resistant. PCR analyses revealed the presence of IS256 in 43/70 S. pseudintemedius isolates. The association between the presence of IS256 and the resistance was particularly significant for certain antibiotics: cefovecin, amikacin, gentamicin and oxacillin (χ(2)p-value<0.05). However, there was a striking result in frequency of strains resistant to gentamicin and oxacillin, suggesting a specific association between the presence of the IS256 element and the determinants for the resistance to these antibiotics. To the best of our knowledge, this is the first report showing the detection of IS256 in S. pseudintermedius isolates and its association with antibiotic resistance. Our findings suggest that S. pseudintermedius may acquire antibiotic resistance genes through mobile genetic elements which may play a predominant role in the dissemination of multi-drug resistance.

  7. A case of blastomycosis-like pyoderma caused by mixed infection of Staphylococcus epidermidis and Trichophyton rubrum.

    PubMed

    Ouchi, Takeshi; Tamura, Mai; Nishimoto, Shuhei; Sato, Tomotaka; Ishiko, Akira

    2011-06-01

    Blastomycosis-like pyoderma (BLP) is a type of chronic pyoderma characterized histologically by specific epidermal changes namely: pseudoepitheliomatous hyperplasia and intraepithelial abscesses. These epidermal changes are also seen in blastomycosis (referred to as deep dermatophytosis in North America). Here, we describe the case of a 53-year-old male with prurigo nodularis, diabetes, and chronic lymphocytic leukemia who presented with multiple yellowish-red colored papules that coalesced to form a vegetating plaque. In addition to the typical features of BLP, spores with budding were seen histopathologically in a biopsy specimen. Cultures of a skin specimen grew Staphylococcus epidermidis and Trichophyton rubrum. Antibiotic therapy was effective but failed to eliminate the lesion until antifungal therapy using terbinafine was administered concurrently. Past reports suggest that BLP is mainly caused by bacterial infection, but our case suggests that fungal infection can also be involved as the causative organism in BLP.

  8. Characterization of a New Epidemic Necrotic Pyoderma in Fur Animals and Its Association with Arcanobacterium phocae Infection

    PubMed Central

    Nordgren, Heli; Aaltonen, Kirsi; Sironen, Tarja; Kinnunen, Paula M.; Kivistö, Ilkka; Raunio-Saarnisto, Mirja; Moisander-Jylhä, Anna-Maria; Korpela, Johanna; Kokkonen, Ulla-Maija; Hetzel, Udo; Sukura, Antti; Vapalahti, Olli

    2014-01-01

    A new type of pyoderma was detected in Finnish fur animals in 2007. The disease continues to spread within and between farms, with severe and potentially fatal symptoms. It compromises animal welfare and causes considerable economic losses to farmers. A case-control study was performed in 2010–2011 to describe the entity and to identify the causative agent. Altogether 99 fur animals were necropsied followed by pathological and microbiological examination. The data indicated that the disease clinically manifests in mink (Neovison vison) by necrotic dermatitis of the feet and facial skin. In finnraccoons (Nyctereutes procyonoides), it causes painful abscesses in the paws. Foxes (Vulpes lagopus) are affected by severe conjunctivitis and the infection rapidly spreads to the eyelids and facial skin. A common finding at necropsy was necrotic pyoderma. Microbiological analysis revealed the presence of a number of potential causative agents, including a novel Streptococcus sp. The common finding from all diseased animals of all species was Arcanobacterium phocae. This bacterium has previously been isolated from marine mammals with skin lesions but this is the first report of A. phocae isolated in fur animals with pyoderma. The results obtained from this study implicate A. phocae as a potential causative pathogen of fur animal epidemic necrotic pyoderma (FENP) and support observations that the epidemic may have originated in a species -shift of the causative agent from marine mammals. The variable disease pattern and the presence of other infectious agents (in particular the novel Streptococcus sp.) suggest a multifactorial etiology for FENP, and further studies are needed to determine the environmental, immunological and infectious factors contributing to the disease. PMID:25302603

  9. Characterization of meticillin-resistant and meticillin-susceptible isolates of Staphylococcus pseudintermedius from cases of canine pyoderma in Australia.

    PubMed

    Siak, Meng; Burrows, Amanda K; Coombs, Geoffrey W; Khazandi, Manouchehr; Abraham, Sam; Norris, Jacqueline M; Weese, J Scott; Trott, Darren J

    2014-09-01

    Meticillin-resistant Staphylococcus pseudintermedius (MRSP) has recently emerged as a worldwide cause of canine pyoderma. In this study, we characterized 22 S. pseudintermedius isolates cultured from 19 dogs with pyoderma that attended a veterinary dermatology referral clinic in Australia in 2011 and 2012. Twelve isolates were identified as MRSP by mecA real-time PCR and phenotypic resistance to oxacillin. In addition to β-lactam resistance, MRSP isolates were resistant to erythromycin (91.6 %), gentamicin (83.3 %), ciprofloxacin (83.3 %), chloramphenicol (75 %), clindamycin (66 %), oxytetracycline (66 %) and tetracycline (50 %), as shown by disc-diffusion susceptibility testing. Meticillin-susceptible S. pseudintermedius isolates only showed resistance to penicillin/ampicillin (90 %) and tetracycline (10 %). PFGE using the SmaI restriction enzyme was unable to type nine of the 12 MRSP isolates. However the nine isolates provided the same PFGE pulsotype using the Cfr91 restriction enzyme. Application of the mec-associated direct repeat unit (dru) typing method identified the nine SmaI PFGE-untypable isolates as dt11cb, a dru type that has only previously been associated with MRSP sequence type (ST)45 isolates that possess a unique SCCmec element. The dt11cb isolates shared a similar multidrug-resistant antibiogram phenotype profile, whereas the other MRSP isolates, dt11a, dt11af (dt11a-associated) and dt10h, were resistant to fewer antibiotic classes and had distinct PFGE profiles. This is the first report of MRSP causing pyoderma in dogs from Australia. The rapid intercontinental emergence and spread of multidrug-resistant MRSP strains confirms the urgent need for new treatment modalities for recurrent canine pyoderma in veterinary practice. © 2014 The Authors.

  10. Evidence that proliferation of golgi apparatus depends on both de novo generation from the endoplasmic reticulum and formation from pre-existing stacks during the growth of tobacco BY-2 cells.

    PubMed

    Abiodun, Moses Olabiyi; Matsuoka, Ken

    2013-04-01

    In higher plants, the numbers of cytoplasmic-distributed Golgi stacks differ based on function, age and cell type. It has not been clarified how the numbers are controlled, whether all the Golgi apparatus in a cell function equally and whether the increase in Golgi number is a result of the de novo formation from the endoplasmic reticulum (ER) or fission of pre-existing stacks. A tobacco prolyl 4-hydroxylase (NtP4H1.1), which is a cis-Golgi-localizing type II membrane protein, was tagged with a photoconvertible fluorescent protein, mKikGR (monomeric Kikume green red), and expressed in tobacco bright yellow 2 (BY-2) cells. Transformed cells were exposed to purple light to convert the fluorescence from green to red. A time-course analysis after the conversion revealed a progressive increase in green puncta and a decrease in the red puncta. From 3 to 6 h, we observed red, yellow and green fluorescent puncta corresponding to pre-existing Golgi; Golgi containing both pre-existing and newly synthesized protein; and newly synthesized Golgi. Analysis of the number and fluorescence of Golgi at different phases of the cell cycle suggested that an increase in Golgi number with both division and de novo synthesis occurred concomitantly with DNA replication. Investigation with different inhibitors suggested that the formation of new Golgi and the generation of Golgi containing both pre-existing and newly synthesized protein are mediated by different machineries. These results and modeling based on quantified results indicate that the Golgi apparatuses in tobacco BY-2 cells are not uniform and suggest that both de novo synthesis from the ER and Golgi division contribute almost equally to the increase in proliferating cells.

  11. Prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) from skin and carriage sites of dogs after treatment of their meticillin-resistant or meticillin-sensitive staphylococcal pyoderma.

    PubMed

    Beck, Karri M; Waisglass, Stephen E; Dick, Hani L N; Weese, J Scott

    2012-08-01

    Meticillin-resistant staphylococci are significant pathogens in veterinary dermatology, yet longitudinal studies of the impact of routine antimicrobial therapy on emergence or resolution of resistance are lacking. To determine the prevalence of meticillin-resistant staphylococci on skin and carriage sites in dogs with bacterial pyoderma and evaluate the prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) colonization after successful treatment of pyoderma. One hundred and seventy-three dogs that presented to a dermatology referral service with pyoderma and 41 healthy control dogs. Skin, nasal and rectal swabs for bacterial culture were collected at the time of referral and after clinical resolution of the pyoderma. Meticillin resistance was confirmed by demonstration of penicillin binding protein 2a antigen. Initially, skin cultures yielded MRSP in 70 (40.5%) dogs, meticillin-resistant Staphylococcus aureus (MRSA) in three (1.7%) and meticillin-resistant Staphylococcus schleiferi ssp. coagulans (MRSScoag) in five (2.9%). Samples collected from the nose and rectum (carriage sites) yielded MRSP in 59 (34.1%) dogs, MRSA in 11 (6.4%) and MRSScoag in seven (4.0%). One hundred and two dogs were available for follow-up cultures after clinical cure. Of 42 dogs initially diagnosed with MRSP pyoderma, MRSP was isolated at follow-up from skin in 19 (45.2%) and carriage sites in 20 (47.6%). Of 60 dogs that did not have MRSP pyoderma initially, MRSP was isolated post-treatment from the skin in 17 (28.3%), and MRSP from carriage sites increased from 7.8% (initially) to 26.7% (P = 0.0022). Colonization by MRSP often persists after resolution of MRSP pyoderma. Acquisition of MRSP during treatment appears to be common. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

  12. The effect of pre-existing health conditions on the cost of recovery from road traffic injury: insights from data linkage of medicare and compensable injury claims in Victoria, Australia.

    PubMed

    Hassani-Mahmooei, Behrooz; Berecki-Gisolf, Janneke; Hahn, Youjin; McClure, Roderick J

    2016-04-29

    Comorbidity is known to affect length of hospital stay and mortality after trauma but less is known about its impact on recovery beyond the immediate post-accident care period. The aim of this study was to investigate the role of pre-existing health conditions in the cost of recovery from road traffic injury using health service use records for 1 year before and after the injury. Individuals who claimed Transport Accident Commission (TAC) compensation for a non-catastrophic injury that occurred between 2010 and 2012 in Victoria, Australia and who provided consent for Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) linkage were included (n = 738) in the analysis. PBS and MBS records dating from 12 months prior to injury were provided by the Department of Human Services (Canberra, Australia). Pre-injury use of health service items and pharmaceuticals were considered to indicate pre-existing health condition. Bayesian Model Averaging techniques were used to identify the items that were most strongly correlated with recovery cost. Multivariate regression models were used to determine the impact of these items on the cost of injury recovery in terms of compensated ambulance, hospital, medical, and overall claim cost. Out of the 738 study participants, 688 used at least one medical item (total of 15,625 items) and 427 used at least one pharmaceutical item (total of 9846). The total health service cost of recovery was $10,115,714. The results show that while pre-existing conditions did not have any significant impact on the total cost of recovery, categorical costs were affected: e.g. on average, for every anaesthetic in the year before the accident, hospital cost of recovery increased by 24 % [95 % CI: 13, 36 %] and for each pathological test related to established diabetes, hospital cost increased by $10,407 [5466.78, 15346.28]. For medical costs, each anaesthetic led to $258 higher cost [174.16, 341.16] and every prescription of drugs

  13. Ecthyma gangrenosum following toxic epidermal necrolysis syndrome in a 3-year-old boy-a survivable series of events.

    PubMed

    Gresik, Christine M; Brewster, Luke P; Abood, Gerard; Supple, Kathy G; Silver, Geoffrey M; Gamelli, Richard L; Nickoloff, Brian J

    2008-01-01

    Toxic epidermal necrolysis syndrome (TENS) is a severe but rare skin reaction leading to epidermal desquamation of greater than 30% of the TBSA. It is most commonly precipitated by the administration of medication. Frequent complications of this syndrome include local wound infections, respiratory, mucocutaneous, and ocular complications. Ecthyma gangrenosum (EG) is a rare disease characterized by a milliary seeding of the cutaneous tissue with Gram-negative bacteria; it is most commonly seen in immunocompromised individuals. Here we report a 3-year-old boy who developed EG subsequent to TENS. Although he had a complicated and prolonged hospital course, he survived these series of events. To our knowledge, this is the first reported case of TENS/EG in the pediatric population, and the first report of survivability following these illnesses.

  14. A case of antibacterial-responsive mucocutaneous disease in a seven-year-old dwarf lop rabbit (Oryctolagus cuniculus) resembling mucocutaneous pyoderma of dogs.

    PubMed

    Benato, L; Stoeckli, M R; Smith, S H; Dickson, S; Thoday, K L; Meredith, A

    2013-04-01

    A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was referred with severe swelling and erythema of the mucocutaneous junctions of the lips, nares and vulva. Bilateral, severe periocular dermatitis was also present. Heavy pure growths of a member of the Staphylococcus intermedius group were cultured from nasal and aural swabs and skin biopsies. Other possible differential diagnoses were eliminated by standard tests. The clinical features and histopathological characteristics of the biopsies were most consistent with mucocutaneous pyoderma, a dermatosis previously reported in dogs but not in rabbits. Treatment of the bacterial infection with oral marbofloxacin and topical ofloxacin eye drops together with supportive therapy resulted in resolution of the lesions. To the authors' knowledge, this is the first report of mucocutaneous bacterial pyoderma, similar to mucocutaneous pyoderma of dogs, in a rabbit. © 2013 British Small Animal Veterinary Association.

  15. The mechanism of Fe(2+)-initiated lipid peroxidation in liposomes: the dual function of ferrous ions, the roles of the pre-existing lipid peroxides and the lipid peroxyl radical.

    PubMed Central

    Tang, L; Zhang, Y; Qian, Z; Shen, X

    2000-01-01

    The mechanism of Fe(2+)-initiated lipid peroxidation in a liposomal system was studied. It was found that a second addition of ferrous ions within the latent period lengthened the time lag before lipid peroxidation started. The apparent time lag depended on the total dose of Fe(2+) whenever the second dose of Fe(2+) was added, which indicates that Fe(2+) has a dual function: to initiate lipid peroxidation on one hand and suppress the species responsible for the initiation of the peroxidation on the other. When the pre-existing lipid peroxides (LOOH) were removed by incorporating triphenylphosphine into liposomes, Fe(2+) could no longer initiate lipid peroxidation and the acceleration of Fe(2+) oxidation by the liposomes disappeared. However, when extra LOOH were introduced into liposomes, both enhancement of the lipid peroxidation and shortening of the latent period were observed. When the scavenger of lipid peroxyl radicals (LOO(.)), N,N'-diphenyl-p-phenylene-diamine, was incorporated into liposomes, neither initiation of the lipid peroxidation nor acceleration of the Fe(2+) oxidation could be detected. The results may suggest that both the pre-existing LOOH and LOO(.) are necessary for the initiation of lipid peroxidation. The latter comes initially from the decomposition of the pre-existing LOOH by Fe(2+) and can be scavenged by its reaction with Fe(2+). Only when Fe(2+) is oxidized to such a degree that LOO(.) is no longer effectively suppressed does lipid peroxidation start. It seems that by taking the reactions of Fe(2+) with LOOH and LOO(.) into account, the basic chemistry in lipid peroxidation can explain fairly well the controversial phenomena observed in Fe(2+)-initiated lipid peroxidation, such as the existence of a latent period, the critical ratio of Fe(2+) to lipid and the required oxidation of Fe(2+). PMID:11062055

  16. Detection of antibody responses against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins in children with community-acquired pneumonia: effects of combining pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness.

    PubMed

    Borges, I C; Andrade, D C; Vilas-Boas, A-L; Fontoura, M-S H; Laitinen, H; Ekström, N; Adrian, P V; Meinke, A; Cardoso, M-R A; Barral, A; Ruuskanen, O; Käyhty, H; Nascimento-Carvalho, C M

    2015-08-01

    We evaluated the effects of combining different numbers of pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness on the detection of IgG responses against eight Streptococcus pneumoniae proteins, three Haemophilus influenzae proteins, and five Moraxella catarrhalis proteins in 690 children aged <5 years with pneumonia. Serological tests were performed on acute and convalescent serum samples with a multiplexed bead-based immunoassay. The median sampling interval was 19 days, the median age was 26.7 months, and the median duration of illness was 5 days. The rate of antibody responses was 15.4 % for at least one pneumococcal antigen, 5.8 % for H. influenzae, and 2.3 % for M. catarrhalis. The rate of antibody responses against each pneumococcal antigen varied from 3.5 to 7.1 %. By multivariate analysis, pre-existing antibody levels showed a negative association with the detection of antibody responses against pneumococcal and H. influenzae antigens; the sampling interval was positively associated with the detection of antibody responses against pneumococcal and H. influenzae antigens. A sampling interval of 3 weeks was the optimal cut-off for the detection of antibody responses against pneumococcal and H. influenzae proteins. Duration of illness was negatively associated with antibody responses against PspA. Age did not influence antibody responses against the investigated antigens. In conclusion, serological assays using combinations of different pneumococcal proteins detect a higher rate of antibody responses against S. pneumoniae compared to assays using a single pneumococcal protein. Pre-existing antibody levels and sampling interval influence the detection of antibody responses against pneumococcal and H. influenzae proteins. These factors should be considered when determining pneumonia etiology by serological methods in children.

  17. The prevalence of the pre-existing hepatitis C viral variants and the evolution of drug resistance in patients treated with the NS3-4a serine protease inhibitor telaprevir

    SciTech Connect

    Rong, Libin; Ribeiro, Ruy M; Perelson, Alan S

    2008-01-01

    Telaprevir (VX-950), a novel hepatitis C virus (HCV) NS3-4A serine protease inhibitor, has demonstrated substantial antiviral activity in patients infected with HCV genotype 1. Some patients experience viral breakthrough, which has been shown to be associated with emergence of telaprevir-resistant HCV variants during treatment. The exact mechanisms underlying the rapid selection of drug resistant viral variants during dosing are not fully understood. In this paper, we develop a two-strain model to study the pre-treatment prevalence of the mutant virus and derive an analytical solution of the mutant frequency after administration of the protease inhibitor. Our analysis suggests that the rapid increase of the mutant frequency during therapy is not due to mutant growth but rather due to the rapid and profound loss of wild-type virus, which uncovers the pre-existing mutant variants. We examine the effects of backward mutation and hepatocyte proliferation on the pre-existence of the mutant virus and the competition between wild-type and drug resistant virus during therapy. We then extend the simple model to a general model with multiple viral strains. Mutations during therapy do not play a significant role in the dynamics of various viral strains, although they are capable of generating low levels of HCV variants that would otherwise be completely suppressed because of fitness disadvantages. Hepatocyte proliferation may not affect the pretreatment frequency of mutant variants, but is able to influence the quasispecies dynamics during therapy. It is the relative fitness of each mutant strain compared with wild-type that determines which strain(s) will dominate the virus population. The study provides a theoretical framework for exploring the prevalence of pre-existing mutant variants and the evolution of drug resistance during treatment with other protease inhibitors or HCV polymerase inhibitors.

  18. Clinical efficacy and safety of cefovecin in the treatment of canine pyoderma and wound infections.

    PubMed

    Stegemann, M R; Coati, N; Passmore, C A; Sherington, J

    2007-07-01

    To determine the efficacy and safety of cefovecin in the treatment of bacterial skin infections in dogs. Dogs with superficial or deep pyoderma or wounds/abscesses were enrolled in three separate studies. Dogs (354) were randomised to treatment and received either cefovecin administered by subcutaneous injection at 14 day intervals, as clinically necessary, or amoxicillin/clavulanic acid as oral tablets twice daily for 14 days. Courses of treatment were repeated at 14 day intervals up to a total of four courses. Clinicians responsible for assessing lesions were masked to treatment allocation. Only animals where the presence of a pretreatment bacterial pathogen was confirmed were included in the analysis of efficacy. Cases were evaluated for clinical efficacy at 28 days after initiation of the final course of treatment. Clinical efficacy was assessed by scoring the clinical signs typical of skin infections. Cefovecin demonstrated statistical non-inferiority compared with amoxicillin/clavulanic acid for all three clinical diagnoses; for cefovecin, up to 96.9 per cent efficacy was observed versus 92.5 per cent for amoxicillin/clavulanic acid. Cefovecin was shown to be as effective as amoxicillin/clavulanic acid administered orally in the treatment of bacterial skin infections in dogs. Cefovecin offers the additional benefit of eliminating owner non-compliance.

  19. Streptococcal Immunity Is Constrained by Lack of Immunological Memory following a Single Episode of Pyoderma

    PubMed Central

    Pandey, Manisha; Ozberk, Victoria; Calcutt, Ainslie; Langshaw, Emma; Powell, Jessica; Rivera-Hernandez, Tania; Philips, Zachary; Batzloff, Michael R.; Good, Michael F.

    2016-01-01

    The immunobiology underlying the slow acquisition of skin immunity to group A streptococci (GAS), is not understood, but attributed to specific virulence factors impeding innate immunity and significant antigenic diversity of the type-specific M-protein, hindering acquired immunity. We used a number of epidemiologically distinct GAS strains to model the development of acquired immunity. We show that infection leads to antibody responses to the serotype-specific determinants on the M-protein and profound protective immunity; however, memory B cells do not develop and immunity is rapidly lost. Furthermore, antibodies do not develop to a conserved M-protein epitope that is able to induce immunity following vaccination. However, if re-infected with the same strain within three weeks, enduring immunity and memory B-cells (MBCs) to type-specific epitopes do develop. Such MBCs can adoptively transfer protection to naïve recipients. Thus, highly protective M-protein-specific MBCs may never develop following a single episode of pyoderma, contributing to the slow acquisition of immunity and to streptococcal endemicity in at-risk populations. PMID:28027314

  20. Towards ethical guidelines for dealing with unsolicited patient emails and giving teleadvice in the absence of a pre-existing patient-physician relationship — systematic review and expert survey

    PubMed Central

    2000-01-01

    Background Many health information providers on the Internet and doctors with email accounts are confronted with the phenomenon of receiving unsolicited emails from patients asking for medical advice. Also, a growing number of websites offer "ask-the-doctor" services, where patients can ask questions to health professionals via email or other means of telecommunication. It is unclear whether these types of interactions constitute medical practice, and whether physicians have the ethical obligation to respond to unsolicited patient emails. Objective To improve the quality of online communication between patients and health professionals (physicians, experts) in the absence of a pre-existing patient-physician relationship or face-to-face communication, by preparing a set of guiding ethical principles applicable to this kind of interaction. Methods Systematic review of the literature, professional, and ethical codes; and consultation with experts. Results Two different types of patient-physician encounters have to be distinguished. "Traditional" clinical encounters or telemedicine applications are called "Type B" interactions here (Bona fide relationship). In comparison, online interactions lack many of the characteristics of bona fide interactions; most notably there is no pre-existing relationship and the information available to the physician is limited if, for example, a physician responds to the email of a patient who he has never seen before. I call these "Type A" consultations (Absence of pre-existing patient-physician relationship). While guidelines for Type B interactions on the Internet exist (Kane, 1998), this is not the case for Type A interactions. The following principles are suggested: Physicians responding to patients' requests on the Internet should act within the limitations of telecommunication services and keep the global nature of the Internet in mind; not every aspect of medicine requires face-to-face communication; requests for help, including

  1. Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non-MRS canine superficial pyoderma: a randomized, blinded, antibiotic-controlled study.

    PubMed

    Borio, Stefano; Colombo, Silvia; La Rosa, Giuseppe; De Lucia, Michela; Damborg, Peter; Guardabassi, Luca

    2015-10-01

    There is a lack of studies comparing topical antiseptics to systemic antibiotics in the treatment of canine superficial pyoderma. To compare the efficacy of topical chlorhexidine with systemic amoxicillin-clavulanic acid for the treatment of canine superficial pyoderma. A randomized controlled trial was conducted in dogs with superficial pyoderma. Group T (n = 31) was treated topically with 4% chlorhexidine digluconate shampoo (twice weekly) and solution (once daily) for 4 weeks. Group S (n = 20) was treated orally with amoxicillin-clavulanic acid (25 mg/kg) twice daily for 4 weeks. Bacterial culture and susceptibility testing were performed on clinical specimens collected before treatment. Severity of lesions and number of intracellular bacteria were evaluated using four-point scales to calculate a total pyoderma score for each dog. Pruritus was assessed by owners using a visual analog scale (range 0-10). Scores were analysed for statistical differences between groups T and S. Staphylococcus pseudintermedius was isolated from 48 dogs, including eight meticillin-resistant strains (MRSP). Although the number of dogs was small, no significant differences in pyoderma and pruritus scores were observed between groups throughout the study except for day 1, when group S had a significantly higher total score than group T (P = 0.03). Treatment with chlorhexidine products resulted in resolution of clinical signs in all dogs including those infected with MRSP. Topical therapy with chlorhexidine digluconate products may be as effective as systemic therapy with amoxicillin-clavulanic acid. This finding supports the current recommendations to use topical antiseptics alone for the management of superficial pyoderma. © 2015 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.

  2. Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.

    PubMed

    Zur, Gila; Soback, Stefan; Weiss, Yfat; Perry, Elad; Lavy, Eran; Britzi, Malka

    2014-04-01

    Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 μg/mL and 1.03 ± 0.43 μg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2).

  3. Deep pyoderma caused by Burkholderia cepacia complex associated with ciclosporin administration in dogs: a case series.

    PubMed

    Banovic, Frane; Koch, Sandra; Robson, David; Jacob, Megan; Olivry, Thierry

    2015-08-01

    Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous Gram-negative bacilli associated with fatal nosocomial infections in humans; multi-antibiotic resistance makes this organism a serious threat in hospital settings. To describe the historical, clinicopathological and treatment characteristics of Bcc-associated deep skin infections in dogs. Six dogs with skin infections in which skin bacterial cultures resulted in pure growth of Bcc. Retrospective study with review of medical records and skin biopsies. All dogs were receiving oral ciclosporin at the time of skin infection development. All dogs were castrated males and four of six were West Highland white terriers. Cutaneous lesions consistent with deep pyoderma were confined mainly to the trunk. In all dogs skin cytology revealed a strong inflammatory response, with moderate to abundant numbers of intracellular (neutrophils and macrophages) and extracellular bacilli. In three dogs histopathology showed a multifocal, nodular to coalescing pyogranulomatous dermatitis associated with multifocal folliculitis and furunculosis. Tissue Giemsa and Gram stains identified numerous Gram-negative rods within macrophages. Antimicrobial susceptibility testing revealed multidrug-resistant Bcc strains with sensitivity to trimethoprim/sulfonamides in all dogs and to marbofloxacin, piperacillin and ceftazidime in three dogs. Successful treatment was achieved in all dogs using trimethoprim/sulfonamides or quinolones (marbofloxacin, ciprofloxacin) or doxycycline in conjunction with ciclosporin withdrawal. Clinicians should be aware of the rare potential for Bcc-associated deep skin infections in dogs receiving oral ciclosporin. Owners should be made conscious of the potential transmission risk to humans or other animals. © 2015 ESVD and ACVD.

  4. A study of community-associated methicillin-resistant Staphylococcus aureus in patients with pyoderma

    PubMed Central

    Venniyil, Prasanth V.; Ganguly, Satyaki; Kuruvila, Sheela; Devi, Sheela

    2016-01-01

    Background: Health care–associated methicillin-resistant Staphylococcus aureus(HA-MRSA) are resistant to multiple antibiotics, therefore infections caused by them are difficult to treat resulting in high morbidity and mortality. While most of the research activities and public health initiatives are focused on HA-MRSA, the newly emerging pathogen, community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) is gaining in significance in respect to patient morbidity. There is a significant paucity of data regarding CA-MRSA in the developing parts of the world. Aim: To study the proportions of HA-MRSA and CA-MRSA infections among patients with culture-proven S. aureus infection and to find out how many of these patients showed presence of MRSA in nasal cultures of healthy contacts. Materials and Methods: Clinical details of 227 patients were recorded in the study, such as the duration and recurrence of the infection, history of antibiotic intake, and the presence of other medical illnesses. A pus swab was taken from each lesion and sent for culture and sensitivity. If the culture grew S. aureus, they were screened for methicillin resistance. A swab from the anterior nares of the healthy contact of each patient, whenever available, was collected and it was screened for MRSA. Results: Furunculosis was most common among the primary pyodermas (53/134; 39. 5%). Out of 239 pus culture samples obtained from 227 patients, 192 (84.58%) grew S. aureus; of these 150 (78.12%) were methicillin-sensitive S. aureus (MSSA), whereas 42 (21.98%) were MRSA. Out of the 42 MRSA isolated, 33 turned out to be CA-MRSA (78%) and 9 (22%) were HA-MRSA. Nasal swabs of healthy contacts of 34 MRSA patients were cultured. Out of them, two grew MRSA in the culture. Conclusion: The isolation rate of S. aureus was high in our study. Furthermore, our study, although hospital based, clearly indicated the substantial magnitude of the CA-MRSA problem in the local population. PMID:27294048

  5. Antimicrobial susceptibility and methicillin resistance in Staphylococcus pseudintermedius and Staphylococcus schleiferi subsp. coagulans isolated from dogs with pyoderma in Japan.

    PubMed

    Kawakami, Tetsuji; Shibata, Sanae; Murayama, Nobuo; Nagata, Masahiko; Nishifuji, Koji; Iwasaki, Toshiroh; Fukata, Tsuneo

    2010-12-01

    To understand species distribution, trends of antimicrobial susceptibility and prevalence of methicillin resistance in canine staphylococci in Japan, 190 coagulase-positive staphylococci (CoPS) were isolated from dogs with pyoderma in 2 Japanese veterinary referral hospitals. Using a multiplex polymerase chain reaction (M-PCR) method, two CoPS species were identified: 170 Staphylococcus pseudintermedius (89.5%) and 20 S. schleiferi subsp. coagulans isolates (10.5%). In these isolates, susceptibility to 7 antimicrobial agents was determined. Overall, the levels of susceptibility to cefalexin (CEX), amoxicillin/clavulanic acid (CVA/AMPC), minocycline (MINO), ofloxacin (OFLX), norfloxacin (NFLX), lincomycin (LCM) and clindamycin (CLDM) in S. pseudintermedius isolates were 38.2, 52.4, 34.7, 31.2, 34.1, 1.2 and 11.2%, respectively. In S. schleiferi subsp. coagulans isolates, 55% demonstrated susceptibility to CEX, 80% to CVA/AMPC, 70% to MINO, 45% to OFLX or NFLX and 30% to CLDM. None of S. schleiferi subsp. coagulans isolates was susceptible to LCM. To determine the prevalence of methicillin-resistant strains, we used a PCR method, which enabled detection of the fragment of mecA gene in 66.5% (113 of 170) in S. pseudintermedius and 30.0% (6 of 20) in S. schleiferi subsp. coagulans isolates. The frequencies of susceptibility to CEX, CVA/AMPC, OFLX, NFLX and CLDM were significantly lower in methicillin-resistant CoPS than in methicillin-susceptible CoPS isolates. These data suggest a high level of methicillin resistance in staphylococci isolated from dogs with pyoderma in Japan.

  6. Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-existing Liver and/or Renal Dysfunction

    PubMed Central

    Sasaki, Koji; Lahoti, Amit; Jabbour, Elias; Jain, Preetesh; Pierce, Sherry; Borthakur, Gautam; Daver, Naval; Kadia, Tapan; Pemmaraju, Naveen; Ferrajoli, Alessandra; O’Brien, Susan; Kantarjian, Hagop; Cortes, Jorge

    2016-01-01

    Summary BACKGROUND The safety and efficacy of frontline nilotinib and dasatinib in newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) patients with pre-existing liver and/or renal dysfunction are unknown. PATIENTS and METHODS We analyzed adverse event rates, response rates, and survival rates of 215 CML-CP patients with or without renal and/or liver dysfunction who were treated with front-line nilotinib (108 patients) or dasatinib (107 patients). RESULTS Overall median follow-up was 49 months. At baseline, 6 (6%) dasatinib-treated patients had mild renal dysfunction and 13 (12%) had mild liver dysfunction. Eight (7%) nilotinib-treated patients had mild renal dysfunction, 1 (1%) had moderate renal dysfunction, and 9 (8%) mild liver dysfunction. There were no significant differences in the rates of complete cytogenetic response, major molecular response, or MR4.5 between organ function cohorts. Dasatinib- or nilotinib- treated patients with baseline renal dysfunction had a higher incidence of transient reversible acute kidney injury (p=0.011; p<0.001), and nilotinib-treated patients with renal dysfunction had a higher incidence of bleeding (p<0.001). CONCLUSION CML-CP patients with mild to moderate renal or liver dysfunction can be safely treated with frontline dasatinib or nilotinib and can achieve response rates similar to those of CML-CP patients with normal organ function. PMID:26796981

  7. Novel application of stereotactic ablative radiotherapy using CyberKnife(®) for early-stage renal cell carcinoma in patients with pre-existing chronic kidney disease: Initial clinical experiences.

    PubMed

    Lo, Cheng-Hsiang; Huang, Wen-Yen; Chao, Hsing-Lung; Lin, Kuen-Tze; Jen, Yee-Min

    2014-07-01

    The treatment of renal cell carcinoma (RCC) in patients diagnosed with chronic kidney disease (CKD) requires particular care in order to preserve the remaining renal function. The present study aimed to investigate the potential of a novel nephron-sparing treatment, which is capable of targeting tumors embedded deep within tissues. The present study analyzed three patients, with pre-existing CKD and multiple comorbidities, who were successfully treated for stage I RCC using the CyberKnife(®) stereotactic ablative radiotherapy (SABR) system. The total prescribed dose was 40 Gy in five fractions administered over five consecutive days. Treatment efficiency was determined using computed tomography scans of the tumors and periodic measurements of the glomerular filtration rate over a period of 12-40 months. Local control, defined as a radiologically stable condition, was achieved in all patients. Lung metastasis was observed in one patient nine months after SABR; however, the side-effects were generally mild and self-limiting. One patient developed renal failure 26 months after SABR, while the severity of CKD was only marginally altered in the other two patients and renal failure did not occur. In conclusion, in the present study, SABR with CyberKnife(®) was observed to be well tolerated in the patients, with an acceptable acute toxicity effect. Therefore, it may represent a potential therapeutic option for patients with early-stage RCC who have previously been diagnosed with CKD, but for whom other nephron-sparing treatments are contraindicated.

  8. One dose of an MF59-adjuvanted pandemic A/H1N1 vaccine recruits pre-existing immune memory and induces the rapid rise of neutralizing antibodies.

    PubMed

    Faenzi, Elisa; Zedda, Luisanna; Bardelli, Monia; Spensieri, Fabiana; Borgogni, Erica; Volpini, Gianfranco; Buricchi, Francesca; Pasini, Franco Laghi; Capecchi, Pier Leopoldo; Montanaro, Fabio; Belli, Riccardo; Lattanzi, Maria; Piccirella, Simona; Montomoli, Emanuele; Ahmed, Syed Sohail; Rappuoli, Rino; Del Giudice, Giuseppe; Finco, Oretta; Castellino, Flora; Galli, Grazia

    2012-06-08

    Protective antibody responses to a single dose of 2009 pandemic vaccines have been observed in the majority of healthy subjects aged more than 3 years. These findings suggest that immune memory lymphocytes primed by previous exposure to seasonal influenza antigens are recruited in the response to A/H1N1 pandemic vaccines and allow rapid seroconversion. However, a clear dissection of the immune memory components favoring a fast response to pandemic vaccination is still lacking. Here we report the results from a clinical study where antibody, CD4+ T cell, plasmablast and memory B cell responses to one dose of an MF59-adjuvanted A/H1N1 pandemic vaccine were analyzed in healthy adults. While confirming the rapid appearance of antibodies neutralizing the A/H1N1 pandemic virus, we show here that the response is dominated by IgG-switched antibodies already in the first week after vaccination. In addition, we found that vaccination induces the rapid expansion of pre-existing CD4+ T cells and IgG-memory B lymphocytes cross-reactive to seasonal and pandemic A/H1N1 antigens. These data shed light on the different components of the immune response to the 2009 H1N1 pandemic influenza vaccination and may have implications in the design of vaccination strategies against future influenza pandemics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Influence of pre-existing fabrics on fault kinematics and rift geometry of interacting segments: Analogue models based on the Albertine Rift (Uganda), Western Branch-East African Rift System

    NASA Astrophysics Data System (ADS)

    Aanyu, K.; Koehn, D.

    2011-02-01

    This study aims at showing how far pre-existing crustal weaknesses left behind by Proterozoic mobile belts, that pass around cratonic Archean shields (Tanzania Craton to the southeast and Congo Craton to the northwest), control the geometry of the Albertine Rift. Focus is laid on the development of the Lake Albert and Lake Edward/George sub-segments and between them the greatly uplifted Rwenzori Mountains, a horst block located within the rift and whose highest peak rises to >5000 m above mean sea level. In particular we study how the southward propagating Lake Albert sub-segment to the north interacts with the northward propagating Lake Edward/George sub-segment south of it, and how this interaction produces the structures and geometry observed in this section of the western branch of the East African Rift, especially within and around the Rwenzori horst. We simulate behaviour of the upper crust by conducting sandbox analogue experiments in which pre-cut rubber strips of varying overstep/overlap connected to a basal sheet and oriented oblique and/or orthogonal to the extension vector, are placed below the sand-pack. The points of connection present velocity discontinuities to localise deformation, while the rubber strips represent ductile domain affected by older mobile belts. From fault geometry of developing rift segments in plan view and section cuts, we study kinematics resulting from a given set of boundary conditions, and results are compared with the natural scenario. Three different basal model-configurations are used to simulate two parallel rifts that propagate towards each other and interact. Wider overstep (model SbR3) produces an oblique transfer zone with deep grabens (max. 7.0 km) in the adjoining segments. Smaller overlap (model SbR4) ends in offset rift segments without oblique transfer faults to join the two, and produces moderately deep grabens (max. 4.6 km). When overlap doubles the overstep (model SbR5), rifts propagate sub-orthogonal to the

  10. Antimicrobial resistance, integron carriage, and gyrA and gyrB mutations in Pseudomonas aeruginosa isolated from dogs with otitis externa and pyoderma in Brazil.

    PubMed

    Arais, Lavicie R; Barbosa, André V; Carvalho, Cristiane A; Cerqueira, Aloysio M F

    2016-04-01

    Pseudomonas aeruginosa is associated with otitis and pyoderma in dogs and is frequently resistant to several antimicrobial drugs. Resistance genes can be carried by integrons with quinolone resistance mainly due to mutations in DNA topoisomerases II and IV. To evaluate the antimicrobial susceptibility, integron carriage, and gyrA and gyrB mutations in P. aeruginosa isolates from canine otitis and pyoderma. One hundred and four P. aeruginosa strains isolated from dogs with otitis externa (n = 93) and pyoderma (n = 11). Antimicrobial susceptibility against 16 antibacterial agents was evaluated through agar diffusion tests. Integron carriage, class and gyrA and gyrB mutations were analysed by PCR, restriction fragment length polymorphism (RFLP)-PCR and genetic sequencing assays. Isolates were mostly resistant to enrofloxacin (72.2%) and ticarcillin (59.7%). Lower resistance to ciprofloxacin (7.7%), tobramycin (3.8%) and polymixin B (0.0%) was detected. Ten (9.6%) multidrug-resistant (MDR) strains were detected. Eight (7.7%) strains carried class 1 integrons and this was associated with MDR (three isolates, P ≤ 0.05). Five of the integron-carrying strains exhibited aminoglycoside resistance genes. Mutations of gyrA and gyrB were observed in 10 isolates, seven of them resistant to all fluoroquinolones tested. Enrofloxacin and ticarcilin resistance was widespread in P. aeruginosa isolated from dogs in Brazil. Pseudomonas aeruginosa carrying integrons may present a significant challenge for treatment. © 2016 ESVD and ACVD.

  11. Identification of a novel Staphylococcus pseudintermedius exfoliative toxin gene and its prevalence in isolates from canines with pyoderma and healthy dogs.

    PubMed

    Iyori, Keita; Hisatsune, Junzo; Kawakami, Tetsuji; Shibata, Sanae; Murayama, Nobuo; Ide, Kaori; Nagata, Masahiko; Fukata, Tsuneo; Iwasaki, Toshiroh; Oshima, Kenshiro; Hattori, Masahira; Sugai, Motoyuki; Nishifuji, Koji

    2010-11-01

    Staphylococcal exfoliative toxins are involved in some cutaneous infections in mammals by targeting desmoglein 1 (Dsg1), a desmosomal cell-cell adhesion molecule. Recently, an exfoliative toxin gene (exi) was identified in Staphylococcus pseudintermedius isolated from canine pyoderma. The aim of this study was to identify novel exfoliative toxin genes in S. pseudintermedius. Here, we describe a novel orf in the genome of S. pseudintermedius isolated from canine impetigo, whose deduced amino acid sequence was homologous to that of the SHETB exfoliative toxin from Staphylococcus hyicus (70.4%). The ORF recombinant protein caused skin exfoliation and abolished cell surface staining of Dsg1 in canine skin. Moreover, the ORF protein degraded the recombinant extracellular domains of canine Dsg1, but not Dsg3, in vitro. PCR analysis revealed that the orf was present in 23.2% (23/99) of S. pseudintermedius isolates from dogs with superficial pyoderma exhibiting various clinical phenotypes, while the occurrence in S. pseudintermedius isolates from healthy dogs was 6.1% (3/49). In summary, this newly found orf in S. pseudintermedius encodes a novel exfoliative toxin, which targets a cell-cell adhesion molecule in canine epidermis and might be involved in a broad spectrum of canine pyoderma.

  12. Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals.

    PubMed

    Balotta, C; Berlusconi, A; Pan, A; Violin, M; Riva, C; Colombo, M C; Gori, A; Papagno, L; Corvasce, S; Mazzucchelli, R; Facchi, G; Velleca, R; Saporetti, G; Galli, M; Rusconi, S; Moroni, M

    2000-03-01

    We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.

  13. The Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) is more useful than pre-existing laboratory tests for predicting hazardous drinking: a cross-sectional study.

    PubMed

    Fujii, Hideki; Nishimoto, Naoki; Yamaguchi, Seiko; Kurai, Osamu; Miyano, Masato; Ueda, Wataru; Oba, Hiroko; Aoki, Tetsuya; Kawada, Norifumi; Okawa, Kiyotaka

    2016-05-10

    It is important to screen for alcohol consumption and drinking customs in a standardized manner. The aim of this study was 1) to investigate whether the AUDIT score is useful for predicting hazardous drinking using optimal cutoff scores and 2) to use multivariate analysis to evaluate whether the AUDIT score was more useful than pre-existing laboratory tests for predicting hazardous drinking. A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted our internal medicine department. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. Forty (23 %) male patients reported daily alcohol consumption ≥ 40 g, and 16 (10 %) female patients reported consumption ≥ 20 g. The optimal cutoff values of hazardous drinking were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2, with a sensitivity of 95.5 %, specificity of 87.0 %, false positive rate of 13.0 %, false negative rate of 4.5 %, and area under the receiver operating characteristic curve of 0.97. Multivariate analysis revealed that the most popular short version of the AUDIT consisting solely of its three consumption items (AUDIT-C) and patient sex were significantly associated with hazardous drinking. The aspartate transaminase (AST)/alanine transaminase (ALT) ratio and mean corpuscular volume (MCV) were weakly significant. This study showed that the AUDIT score and particularly the AUDIT-C score were more useful than the AST/ALT ratio and MCV for predicting hazardous drinking.

  14. Effect of catheter ablation and periprocedural anticoagulation regimen on the clinical course of migraine in atrial fibrillation patients with or without pre-existent migraine: results from a prospective study.

    PubMed

    Mohanty, Sanghamitra; Mohanty, Prasant; Rutledge, J Neal; Di Biase, Luigi; Yan, Rachel Xue; Trivedi, Chintan; Santangeli, Pasquale; Bai, Rong; Cardinal, Deb; Burkhardt, J David; Gallinghouse, Joseph G; Horton, Rodney; Sanchez, Javier E; Bailey, Shane; Hranitzky, Patrick M; Zagrodzky, Jason; Al-Ahmad, Amin; Natale, Andrea

    2015-04-01

    We examined the influence of catheter ablation and periprocedural anticoagulation regimen on trajectory of migraine in atrial fibrillation patients with or without migraine history. Forty patients with (group 1: 64 ± 8 years; men 78%) and 85 (group 2: 61 ± 10 years; men 73%) without migraine history undergoing atrial fibrillation-ablation were enrolled. Migraine status and quality of life were evaluated using standardized questionnaires. Diffusion magnetic resonance imaging of brain was performed for all at pre and 24 hours post procedure. Catheter ablation was performed with (88, 70%) or without (37, 30%) continuous warfarin treatment. Fifty-four patients (11 and 43 from groups 1 and 2, respectively) had subtherapeutic international normalized ratio on procedure day. At 17 ± 5 months follow-up, from group 1, 25 (63%) reported no migraine, 10 (25%) had < 1, and 3 (8%) had 2 to 3 monthly symptoms. Intensity of pain decreased from baseline 7 (Q1-Q3, 4-8) to 2 (0-4) scale points at follow-up (P < 0.001) and duration of headache from median 8 (Q1-Q3, 4-15) to 0.5 (Q1-Q3, 0-2) hours (P < 0.001). Two patients from group 1 reported increased migraine severity and 2 from group 2 had new-onset migraine. Follow-up diffusion magnetic resonance imaging revealed new infarcts in 9.6% (12/125) patients; of which 11 had subtherapeutic preprocedural international normalized ratio on or off continuous warfarin. Quality of life improved significantly in patients with successful ablation, being more pronounced in group 1. In most patients, migraine symptoms improved substantially after catheter ablation. Interestingly, the only cases of new migraine and aggravation of pre-existent headache had subtherapeutic international normalized ratio during the procedure and new cerebral infarcts. © 2015 American Heart Association, Inc.

  15. 3-D numerical modelling of the influence of reactivated pre-existing faults on the distribution of deformation: example of North-Western Ghana around 2.15-2.00 Ga

    NASA Astrophysics Data System (ADS)

    FENG, Xiaojun; Gerbault, Muriel; Martin, Roland; Ganne, Jérôme; Jessell, Mark

    2015-04-01

    High strain zones appear to play a significant role in feeding the upper crust with fluids and partially molten material from lower crust sources. The Bole-Bulenga terrain (North-Western Ghana) is located in between two subvertical shear zones, and mainly consists of high-grade orthogneisses, paragneisses and metabasites intruded by partially molten lower crustal material with monzogranites and orthogneisses (Eburnean orogeny, around 2.1 Ga). In order to understand the location of these high grade rocks at the edges and in between these two shear zones, a three dimensional numerical model was built to test the influence of different orientations of a system of branched strike-slip faults on visco-plastic deformation, under compressional and simple shear boundary conditions. Our models indicate domains of tensile vs. compressional strain as well as shear zones, and show that not only internal fault zones but also the host rock in between the faults behave relatively softer than external regions. Under both applied compressive and simple shear boundary conditions, these softened domains constitute preferential zones of tensile strain accommodation (dilation) in the upper crust, which may favor infilling by deeper partially molten rocks. Our modeled pre-existing faults zones are assumed to have formed during an early D1 stage of deformation, and they are shown to passively migrate and rotate together with the solid matrix under applied external boundary conditions (corresponding to a post D1 - early D2 phase of deformation). We suggest that in the Bole-Bulenga terrain, fluids or partially molten material stored in deeper crustal domains, preferentially intruded the upper crust within these highly (shear and tensile) strained domains, thanks to this D2 shearing deformation phase. Building relief at the surface is primarily controlled by fault orientations, together with mechanical parameters and external boundary conditions. In particular, greatest magnitudes of relief

  16. Tectonic inheritance in the development of the Kivu - north Tanganyika rift segment of the East African Rift System: role of pre-existing structures of Precambrian to early Palaeozoic origin.

    NASA Astrophysics Data System (ADS)

    Delvaux, Damien; Fiama Bondo, Silvanos; Ganza Bamulezi, Gloire

    2017-04-01

    The present architecture of the junction between the Kivu rift basin and the north Tanganyika rift basin is that of a typical accommodation zone trough the Ruzizi depression. However, this structure appeared only late in the development of the Western branch of the East African Rift System and is the result of a strong control by pre-existing structures of Precambrian to early Palaeozoic origin. In the frame of a seismic hazard assessment of the Kivu rift region, we (Delvaux et al., 2016) constructed homogeneous geological, structural and neotectonic maps cross the five countries of this region, mapped the pre-rift, early rift and Late Quaternary faults and compiled the existing knowledge on thermal springs (assumed to be diagnostic of current tectonic activity along faults). We also produced also a new catalogue of historical and instrumental seismicity and defined the seismotectonic characteristics (stress field, depth of faulting) using published focal mechanism data. Rifting in this region started at about 11 Ma by initial doming and extensive fissural basaltic volcanism along normal faults sub-parallel to the axis of the future rift valley, as a consequence of the divergence between the Nubia and the Victoria plate. In a later stage, starting around 8-7 Ma, extension localized along a series of major border faults individualizing the subsiding tectonic basins from the uplifting rift shoulders, while lava evolved towards alkali basaltic composition until 2.6 Ma. During this stage, initial Kivu rift valley was extending linearly in a SSW direction, much further than its the actual termination at Bukavu, into the Mwenga-Kamituga graben, up to Namoya. The SW extremity of this graben was linked via a long oblique transfer zone to the central part of Lake Tanganyika, itself reactivating an older ductile-brittle shear zone. In the late Quaternary-early Holocene, volcanism migrated towards the center of the basin, with the development of the Virunga volcanic massif

  17. Experimental Infection of Mink Enforces the Role of Arcanobacterium phocae as Causative Agent of Fur Animal Epidemic Necrotic Pyoderma (FENP)

    PubMed Central

    Nordgren, Heli; Aaltonen, Kirsi; Raunio-Saarnisto, Mirja; Sukura, Antti; Vapalahti, Olli; Sironen, Tarja

    2016-01-01

    Fur Animal Epidemic Necrotic Pyoderma (FENP) is a severe, often lethal infectious disease affecting all three fur animal species: mink (Neovision vision), foxes (Vulpes lagopus) and finnraccoons (Nyctereutes procyonoides). Previous studies showed an association between Arcanobacterium phocae and FENP. An experimental infection was conducted to confirm the ability of A. phocae to infect mink either alone or concurrently with a novel Streptococcus sp. found together with A. phocae in many cases of FENP. Different inoculation methods were tested to study possible routes of transmission. Typical signs, and gross- and histopathological findings for FENP were detected when naïve mink were infected with the tissue extract of mink with FENP, using a subcutaneous/ intradermal infection route. Edema, hemorrhage, necrosis and pus formation were detected in the infection site. A pure culture preparation of A. phocae alone or concurrently with the novel Streptococcus sp. caused severe acute signs of lethargy, apathy and anorexia and even mortality. The histopathological findings were similar to those found in naturally occurring cases of FENP. In contrast, the perorally infected mink presented no clinical signs nor any gross- or histopathological lesions. This study showed that A. phocae is able to cause FENP. The study also indicated that predisposing factors such as the environment, the general condition of the animals, temperature and skin trauma contribute to the development of the disease. PMID:27973532

  18. Investigations into the basis of chloramphenicol and tetracycline resistance in Staphylococcus intermedius isolates from cases of pyoderma in dogs.

    PubMed

    Kim, T J; Na, Y R; Lee, J I

    2005-04-01

    A total of 160 Staphylococcus intermedius isolates were recovered from cases of pyoderma in 2002 and were examined for susceptibility to 13 different antimicrobial agents. Ninety per cent (144) of the isolates were resistant to tetracycline, derivatives of which have been used until recently, and 18% (29) were resistant to chloramphenicol which was banned from use 13 years ago. The presence of genes encoding chloramphenicol acetyltransferase (CAT) and tetracycline resistance (tet); tet(K), (L), (M), and (O) were determined by PCR in the 29 chloramphenicol and tetracycline resistant isolates. Seventeen (59%) isolates contained the cat gene while 12 (41%) isolates did not carry the cat gene, implying there may be other genes for chloramphenicol resistance that were not detected by the primers (primer set 1) used in this study. The tet(M) gene was found in 28 (97%) of the resistant S. intermedius isolates, but none contained the tet(O) gene. All 29 isolates carried one or two tet genes; tet(K), (L), and (M), with four different distribution patterns. New PCR products, a 1.1 kb product using primer set 1 and a 0.2 kb product using primer set 2, were cloned and sequenced. A 904 bp fragment of S. aureus plamid pS194, including sequence from the streptomycin adenyltransferase gene (804 bp), was found inserted into the terminal region of the cat gene (GenBank accession no. AY604739), whilst the sequence of 0.2 kb was previously unpublished.

  19. Prevalence of and risk factors for isolation of meticillin-resistant Staphylococcus spp. from dogs with pyoderma in northern California, USA.