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Sample records for pre-existing pyoderma gangrenosum

  1. Peristomal pyoderma gangrenosum.

    PubMed

    Keltz, M; Lebwohl, M; Bishop, S

    1992-08-01

    A patient with Crohn's disease and peristomal pyoderma gangrenosum is described. This patient is unique because she had a rapid response to intralesionally injected steroids. This treatment is ideal for peristomal pyoderma gangrenosum because it is administered intermittently when the ostomy appliance is changed and it does not interfere with adhesion of the device. All 11 cases of peristomal pyoderma gangrenosum described in the literature are reviewed. PMID:1387659

  2. Pyoderma gangrenosum in ulcerative colitis.

    PubMed

    Misra, S P; Singh, S K; Chari, S T; Sarin, S K; Anand, B S

    1991-07-01

    We present a patient with pyoderma gangrenosum, a rare complication of ulcerative colitis. The patient's disease was limited to the distal colon, was clinically mild and responded quickly to treatment, and yet it was associated with pyoderma gangrenosum and arthritis, complications generally associated with more severe and extensive ulcerative colitis. PMID:1839305

  3. Sporotrichosis presenting as pyoderma gangrenosum.

    PubMed

    Liao, W Q; Zang, Y L; Shao, J Z

    1991-12-01

    A 56-year-old female with an eight-year history of corticosteroid therapy for rheumatoid arthritis presented with large, deep, painful ulcers on the left buttock and thigh. The lesions appeared typical of pyoderma gangrenosum. Nine separate cultures of the exudate grew Sporothrix schenckii. During the course of iodide therapy, the patient expired due to Escherichia coli pneumonia. This is the third case report of sporotrichosis presenting as pyoderma gangrenosum and the first report from China. Sporotrichosis presenting as pyoderma gangrenosum is a special form of this disease. It develops quickly and must be treated promptly. Only two cases have been reported in the world literature. This is the first case reported from China. PMID:1795732

  4. Pyoderma gangrenosum following reduction mammaplasty

    PubMed Central

    Simon, Amy M; Khuthaila, Dana; Hammond, Dennis C; Andres, Albert

    2006-01-01

    The failure of a postoperative local infection to resolve after appropriate antibiotic therapy should prompt consideration of other diagnoses. Reported here is a case of pyoderma gangrenosum, a rare necrotizing disorder, occurring after reduction mammaplasty. The clinical presentation was one of progressive wound deterioration with associated erythema and intense pain. After failure of antibiotic therapy and local wound care, tissue biopsy of the enlarging wound edge confirmed the diagnosis, which then responded rapidly to systemic steroid treatment. Given that the treatment for pyoderma gangrenosum is at odds with the standard treatment for an infection (steroids versus antibiotics), differentiating between the two diagnoses is vital to providing resolution of the process and limiting any untoward scarring resulting from the advancing open wounds that can develop. With this in mind, the physical signs and symptoms that characterize this condition and thus allow early diagnosis are presented, and treatment options discussed. PMID:19554230

  5. 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. PMID:24769650

  6. 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

  7. Pyoderma gangrenosum induced by episiotomy.

    PubMed

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

    2016-01-01

    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. PMID:26786531

  8. 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

  9. 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. PMID:26779805

  10. Pulmonary pyoderma gangrenosum without cutaneous manifestations.

    PubMed

    Sakata, Kenneth Kazuto; Penupolu, Sudheer; Colby, Thomas Vail; Gotway, Michael Bruce; Wesselius, Lewis Jon

    2016-07-01

    Pyoderma gangrenosum is a chronic sterile skin disorder that is frequently seen in association with systemic disorders such as inflammatory bowel disease. Extracutaneous pyoderma gangrenosum is rare and most commonly occurs in the lungs. It is particularly unusual for extracutaneous pyoderma gangrenosum to manifest prior to skin findings and without an associated systemic disorder. A 19-year-old white man presented with shortness of breath and a productive cough. His skin exam was normal. Unenhanced chest computed tomography showed peripheral consolidations, areas of cavitation, nodules and bilateral pleural effusions. A bronchoalveolar lavage and an autoimmune panel were unremarkable. Right lung wedge biopsies via thoracostomy was performed and showed pulmonary pyoderma gangrenosum. He was treated with corticosteroids and has returned back to his baseline. This is the first case of pulmonary pyoderma gangrenosum without any associated underlying systemic disorder and without any cutaneous manifestations to date. Serial follow-ups are necessary to assess for the development of an associated systemic disorder or skin lesions. PMID:25354722

  11. 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

  12. 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

  13. 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. PMID:25024856

  14. Pyoderma gangrenosum – a review

    PubMed Central

    Wollina, Uwe

    2007-01-01

    Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis. Clinically it starts with sterile pustules that rapidly progress and turn into painful ulcers of variable depth and size with undermined violaceous borders. The legs are most commonly affected but other parts of the skin and mucous membranes may also be involved. Course can be mild or malignant, chronic or relapsing with remarkable morbidity. In many cases PG is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatic or haematological disease and malignancy. Diagnosis of PG is based on history of an underlying disease, typical clinical presentation, histopathology, and exclusion of other diseases that would lead to a similar appearance. The peak of incidence occurs between the ages of 20 to 50 years with women being more often affected than men. Aetiology has not been clearly determined yet. The treatment of PG is a challenge. Randomized, double-blinded prospective multicenter trials for PG are not available. The best documented treatments are systemic corticosteroids and ciclosporin A. Combinations of steroids with cytotoxic drugs are used in resistant cases. The combination of steroids with sulfa drugs or immunosuppressants has been used as steroid-sparing modalities. Anti-tumor necrosis alpha therapy in Crohn's disease showed a rapid response of PG. Skin transplants and the application of bioengineered skin is useful in selected cases as a complement to the immunosuppressive treatment. Topical therapy with modern wound dressings is useful to minimize pain and the risk of secondary infections. Despite recent advances in therapy, the prognosis of PG remains unpredictable. PMID:17433111

  15. A Second Case of Sunitinib-associated Pyoderma Gangrenosum

    PubMed Central

    Dean, Steven M.

    2010-01-01

    Pyoderma gangrenosum is a painful, noninfectious, ulcerative, cutaneous disorder that most commonly affects the lower extremities. The diagnosis is made by recognizing the characteristic clinical manifestations in the setting of a causative systemic disease and excluding other causes of similar-appearing ulcerations. Pyoderma gangrenosum often evolves in the setting of systemic illnesses, such as inflammatory bowel disease, rheumatological disorders, and hematological conditions. However, several medications have rarely been linked to pyoderma gangrenosum. The authors report the second case of sunitinib-associated pyoderma gangrenosum in a 61-year-old patient with recurrent renal cell carcinoma. PMID:20877540

  16. 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

  17. 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. PMID:26891139

  18. 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. PMID:24986794

  19. [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. PMID:26169896

  20. Neutrophilic dermatoses: pyoderma gangrenosum and Sweet's syndrome.

    PubMed Central

    Lear, J. T.; Atherton, M. T.; Byrne, J. P.

    1997-01-01

    Pyoderma gangrenosum and Sweet's syndrome are classified as neutrophilic dermatoses as they exhibit intense dermal inflammatory infiltrates composed of neutrophils with little evidence of a primary vasculitis. They share several characteristics and respond to immunosuppressives. Aetiology is felt to represent a manifestation of altered immunologic reactivity. Patients with both conditions concurrently have been described. Diagnosis is based on clinical and histopathological findings. However, clinically the typical forms of the two conditions are quite distinct: pyoderma showing cutaneous ulceration with a purple undermined border and Sweet's syndrome having tender, erythematous, nonulcerated plaques and nodules. Approximately 50% of cases of pyoderma are associated with a specific systemic disorder. These include inflammatory bowel disease, rheumatoid arthritis, non-Hodgkin's lymphoma and myeloproliferative disorders. Many associations with Sweet's syndrome have been described, including acute myeloid leukaemia, myeloma and adenocarcinomas, and haematological malignancy. There is overlap between the two conditions with lesions categorised as Sweet's syndrome being clinically more characteristic of atypical pyoderma and vice versa. We believe that pyoderma and Sweet's syndrome represent a continuum of spectrum of disease. The reason for the clinical differences between the conditions is unclear and merits further investigation but may be explained by varying levels of intensity and extent of the inflammatory process. This review will describe the pathogenesis, clinical features, diagnosis, associations and treatment of the two conditions. Images Figure 1 Figure 2 PMID:9122099

  1. Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma).

    PubMed

    Mantovani, Lucia; Zauli, Stefania; Sarno, Oriele; Querzoli, Patrizia; Corazza, Monica; Virgili, Annarosa

    2013-06-01

    A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed. As retreatment with oral methylprednisolone induced glucose intolerance and high arterial pressure, sulfa drugs were initially employed with a transitory recovery of the skin lesion. A successive prolonged course with minocycline induced a new complete resolution. To date, at six months' follow-up, the patient is relapse-free. This case confirms that sulfa drugs and minocycline may also be considered alternative therapies in PM. PM is a variety of PG characterized by specific morphological features, a higher tendency to relapse, and poor responsiveness to treatment. PMID:23330662

  2. Postoperative pyoderma gangrenosum: A rare complication after appendectomy

    PubMed Central

    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. PMID:25511218

  3. Pyoderma gangrenosum in a newborn - Case report*

    PubMed Central

    Carneiro, Francisca Regina Oliveira; dos Santos, Maria Amélia Lopes; de Sousa, Brena Andrade; do Nascimento, Carla do Socorro Silva; Amin, Gabriela Athayde; Moutinho, Ana Thais Machado

    2013-01-01

    Pyoderma gangrenosum is a rare, inflammatory, chronic and recurrent disease of unknown etiology, characterized by noninfectious, necrotizing and painful cutaneous ulcers. Usually it affects adults aged between 25 and 54 years old and rarely children (less than 4%), in which it mainly affects the head, face, buttocks, genital and perianal region. The disease presents a quick response to systemic corticosteroids. We report a case of a newborn with hemorrhagic and necrotic ulcers, distributed in the abdomen, buttocks and genital region with rapid and effective response to oral prednisone. PMID:24346911

  4. Pustular pyoderma gangrenosum: an uncommon variant which is easily misdiagnosed.

    PubMed

    Chia, M W; Teo, L; Tay, Y K; Poh, W T

    2008-01-01

    Pustular pyoderma gangrenosum is a relatively uncommon clinical form of pyoderma gangrenosum; it presents with vesiculo-pustular lesions that do not develop into frank ulceration. We report a case of a 44-year-old man with associated ulcerative colitis, who was misdiagnosed as having necrotizing fasciitis. He underwent multiple debridements and a subsequent skin grafting procedure, but without improvement. The diagnosis of pyoderma gangrenosum is often challenging because there is no defining diagnostic clinical, laboratory, or histopathological feature. A high index of suspicion is, therefore, essential to diagnose pyoderma gangrenosum clinically because failure to do so in the early stages of the disease can lead to disfigurement and even unnecessary and detrimental surgery. PMID:18700124

  5. Fatal Pyoderma Gangrenosum with Pathergy after Coronary Artery Bypass Grafting

    PubMed Central

    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. PMID:23304049

  6. [A non-infectious pyodermatitis: Pyoderma gangrenosum].

    PubMed

    Lambert, J; Jonlet, F; Vanhooteghem, O; Richert, B; de la Brassinne, M

    2001-02-01

    Pyoderma gangrenosum (PG) is a rare chronic inflammatory skin disease characterized by the recurring development of necrotizing and painful ulcers. The skin lesions appear spontaneously or after minor traumatic injuries. Sites of predilection include the lower limbs and the trunk but any part of the body may be affected. PG is not an infectious disease; although the etiology is not completely understood, an immune disturbance is certainly involved. An underlying systemic disorder is associated in up to 50% of the cases, specially inflammatory bowel diseases, arthritis, paraproteinemias and hematologic malignancies. Chronic venous or arterial ulcers as well as bacterial gangrene are the most frequent false diagnoses. A right diagnosis, based upon the distinctive clinical features and a compatible histology, is essential to avoid surgical procedure that often tends to exacerbed the process. Because of its persistent and recurrent nature, systemic long-term therapy based upon corticosteroids associated with sulfones or immunosuppressive agents is required. PMID:11294044

  7. 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

  8. Nasal septum perforation in patient with pyoderma gangrenosum

    PubMed Central

    Maia, Camilla Bezerra da Cruz; Felix, Felippe; Paes, Vania; de Azevedo, Julia Alves; Grangeiro, Eliza Raquel Negrão; Riccio, Jonatah Lucas N.; Rito, Helen Cruz

    2012-01-01

    Summary Introduction: The cocaine is obtained from the leaves of the coca (Erythroxylon coca). It can be used in many ways, but the most common is the drug inhalation. The Cocaine also causes vasoconstriction at nasal mucous membrane and its chronic use can cause necrosis and nasal septum perforation. Pyoderma gangrenosum is an uncommon idiopathic disease characterized by ulcerations, usually observed on the legs. Its diagnosis is most common an exclusion of others diseases. So far, there is no specific treatment based on evidence by randomized controlled trials. Objective: Describe the rare association between Pyoderma gangrenosum and cocaine. Case Report: E. A., 27-year-old woman with destruction of nasal septum and palate who has been using a big amount of cocaine, been necessary note the difference from which disease cause de damage. Final Comments: Also there are only three cases of Pyoderma gangrenosum complicated with nasal septum perforation in cocaine users. PMID:25991946

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

    PubMed

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

    2016-01-01

    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 gangrenosum in their differential diagnosis, especially in the setting of a nonhealing surgical wound or skin infection. PMID:27345376

  10. Successful treatment of postoperative pyoderma gangrenosum with cyclosporin.

    PubMed

    Schöfer, H; Baur, S

    2002-03-01

    Postoperative pyoderma gangrenosum (PPG), also known as postoperative progressive gangrene of Cullen, is a rare and rapidly evolving complication of surgical procedures. Since the first description by Cullen in 1924 (Surg Gynecol Obstet 1924; 38: 579-582) various case reports have been published. Even in typical cases PPG is often misdiagnosed and therefore wrongly treated; the unknown aetiology makes treatment difficult. The therapies used for pyoderma gangrenosum include systemic corticosteroids, azathioprine, dapsone, mercaptopurine, sulphasalazine, sulphapyridine, thalidomide, cyclophosphamide, clofazimine, isotretinoin, immunoglobulins and cyclosporin. We report on two patients with PPG following breast surgery who were successfully treated with low-dose cyclosporin (2.5-5 mg/kg per day). PMID:12046819

  11. All that is red is not cellulitis. Pyoderma gangrenosum.

    PubMed

    Sharma, Prashant; Dhungel, Sourab

    2014-02-01

    A 60-year-old patient presented with progressive worsening, non-healing ulcer on her shin with surrounding erythema following a minor trauma and was treated with several antibiotics for presumed cellulitis with no improvement. A skin biopsy eventually suggested pyoderma gangrenosum and a colonic biopsy showed an underlying ulcerative colitis. PMID:24393443

  12. Pyoderma gangrenosum after totally implanted central venous access device insertion

    PubMed Central

    Inan, Ihsan; Myers, Patrick O; Braun, Rolf; Hagen, Monica E; Morel, Philippe

    2008-01-01

    Background Pyoderma gangrenosum is an aseptic skin disease. The ulcerative form of pyoderma gangrenosum is characterized by a rapidly progressing painful irregular and undermined bordered necrotic ulcer. The aetiology of pyoderma gangrenosum remains unclear. In about 70% of cases, it is associated with a systemic disorder, most often inflammatory bowel disease, haematological disease or arthritis. In 25–50% of cases, a triggering factor such as recent surgery or trauma is identified. Treatment consists of local and systemic approaches. Systemic steroids are generally used first. If the lesions are refractory, steroids are combined with other immunosuppressive therapy or to antimicrobial agents. Case presentation A 90 years old patient with myelodysplastic syndrome, seeking regular transfusions required totally implanted central venous access device (Port-a-Cath®) insertion. Fever and inflammatory skin reaction at the site of insertion developed on the seventh post-operative day, requiring the device's explanation. A rapid progression of the skin lesions evolved into a circular skin necrosis. Intravenous steroid treatment stopped the necrosis' progression. Conclusion Early diagnosis remains the most important step to the successful treatment of pyoderma gangrenosum. PMID:18325095

  13. Concurrent pyoderma gangrenosum and infection with Scedosporium apiospermum.

    PubMed

    Tilakaratne, Dev; Ryan, Emma; Pearce, Annette

    2016-05-01

    We present a patient with pyoderma gangrenosum (PG) following hip surgery, who developed an exacerbation of her ulceration in conjunction with new areas on her lower limbs. Clinically, features of PG and deep fungal infection were apparent. Scedosporium apiospermum was isolated from the ulcers. PMID:25920922

  14. Pyoderma Gangrenosum: A Report of 27 Patients.

    PubMed

    Adışen, Esra; Erduran, Funda; Gürer, Mehmet Ali

    2016-06-01

    The aim of this study was to document the profile of pyoderma gangrenosum (PG) patients who were treated in our clinic and to compare our patients' clinical and demographic characteristics with those described in the literature to help our understanding of the total burden of PG. A total of 27 (17 women, 10 men) patients with a mean age 48.6 years at diagnosis were included in the study. Seven (25.9%) of them had 3 or more ulcers. The lower extremity was the most common site of occurrence (92.5%). During the study period, 6 patients were admitted twice, and 7 were admitted 3 or more times (range 1 to >10), and the median length of stay was 27 days. A concomitant disease was present in PG patients especially in those between 20 and 40 years of age. Systemic therapy was used in 21 (91.3%) patients, 17 patients were treated with systemic corticosteroids, either alone in 7 patients or combination with other agents in 10 patients. Three of our patients died because of disease or treatment-related complications during the study period. Despite the high (70.3%) percentage of the PG patients with improving disease at the time of discharge, 1 year after hospital discharge, one third of our 27 patients still had PG requiring readmission. In conclusion, none of the current therapies provide satisfying results in all of the patients, and our data indicate a long-standing unmet need for effective therapy for the unexpected course of PG. PMID:27009790

  15. Concurrent hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of the scalp, and pyoderma gangrenosum in a 16-year-old boy.

    PubMed

    Koshelev, Misha V; Garrison, Paige A; Wright, Teresa S

    2014-01-01

    We report the case of a 16-year-old boy who presented to our clinic with concomitant hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of the scalp, and pyoderma gangrenosum. Recent reports describe the co-occurrence of pyoderma gangrenosum, acne, and hidradenitis suppurativa. This case further expands the spectrum of concomitant pyoderma gangrenosum and dissecting cellulitis of the scalp. PMID:24118007

  16. Bromoderma mimicking pyoderma gangrenosum caused by commercial sedatives.

    PubMed

    Oda, Fumiko; Tohyama, Mikiko; Murakami, Akiko; Kanno, Kazuhisa; Sonobe, Naomi; Sayama, Koji

    2016-05-01

    Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides. PMID:26507105

  17. Pyoderma gangrenosum mimicking a diabetic foot infection: a case report.

    PubMed

    Lee, Ho Seong; Choi, Young Rak; Ha, Sung Hoon; Jeong, Jae Jung

    2013-01-01

    An adult with ulcerative colitis and diabetes presented with a painful, swollen, edematous left foot. Diagnostic images and laboratory tests were inconclusive. Antibiotics were started immediately but aggravated his symptoms, and the laboratory results worsened. His foot was debrided twice per protocol for treating diabetic foot ulcers or cellulitis. After debridement, his condition worsened rapidly. Pyoderma gangrenosum was correctly diagnosed on the basis of massive neutrophilic infiltration detected in the biopsy tissue and because the lesion was well-defined and colored deep red to violet, unlike the bullosis diabeticorum blisters observed in the diabetic foot. His foot improved with systemic corticosteroids and topical wound care, and a skin defect was treated with a skin graft. After 9 months, his foot was well healed. Pyoderma gangrenosum can be diagnosed by careful examination and must be distinguished from an ulcerated diabetic foot lesion. PMID:23073270

  18. Bullous pyoderma gangrenosum associated with pancytopenia of unknown origin

    PubMed Central

    Wolska, Katarzyna; Michalska-Jakubus, Małgorzata; Pucuła, Joanna; Chodorowska, Grażyna; Dzida, Grzegorz; Mosiewicz, Jerzy; Prystupa, Andrzej; Podhorecka, Monika

    2014-01-01

    Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown origin. Clinically it starts with a pustule, nodule or bulla that rapidly progresses and turns into a painful ulcer with raised, undermined borders. The etiopathogenesis of PG remains unknown. However it is frequently associated with systemic diseases such as inflammatory bowel disease (IBD), haematological disorders or arthritis. The latest multicentric retrospective analysis published by Ghazal et al. shows that anaemia has been observed very often in German patients suffering from PG (in 45.6% of 259) so this disorder is supposed to be a possible cofactor in the pathogenesis of PG. According to its progressive course, patients require intensive diagnostic procedures and rapid initiation of the treatment. In this article, we report a case of bullous pyoderma gangrenosum in association with pancytopenia of unknown origin, according to its diagnostic and therapeutic difficulties. PMID:25254015

  19. Pyoderma Gangrenosum-A New Manifestation of Wilson Disease?

    PubMed

    Freg, George Naiem Ibrahiem; Shah, Venisha; Nagral, Aabha; Jhaveri, Ajay

    2016-03-01

    Seventeen year old girl, a known case of Wilson disease presented to us with a non-healing skin ulcer followed by appearance of jaundice, ascites and progressive fatigue of 1 month duration. She was diagnosed to have Wilson disease 5 years back and had been well controlled on d-penicillamine. On enquiry, she was found to be noncompliant with her medication in the preceding 6 months. On examination, she had severe pallor, icterus with moderate ascites and oedema feet. Investigations revealed severe haemolytic anemia and deranged liver function. The lesion was diagnosed to be pyoderma gangrenosum on skin biopsy. The appearance of a cutaneous lesion followed by deterioration in the liver disease and hemolysis suggested uncontrolled Wilson disease as the triggering factor. Chelation therapy improved her haemoglobin and liver function as well as led to healing of the ulcer. We describe pyoderma gangrenosum as a new manifestation of Wilson disease. PMID:27194899

  20. [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. PMID:25627229

  1. 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. PMID:26711368

  2. Fatal pyoderma gangrenosum in association with C7 deficiency.

    PubMed

    Friduss, S R; Sadoff, W I; Hern, A E; Fivenson, D P

    1992-08-01

    Although pyoderma gangrenosum (PG) is often associated with systemic diseases, it has not been reported in association with congenital complement deficiencies. We describe an aggressive and ultimately fatal case of PG in a patient with a congenital C7 deficiency. Deficiencies of C7 can be associated with decreased neutrophil chemotaxis, phagocytosis, and opsonization, similar to the immunologic abnormalities described in patients with PG. Our patient's decreased complement level, if not directly related to the development of PG, may have contributed to the aggressive nature of her disease. PMID:1517503

  3. [Pyoderma gangrenosum, an etiology of chronic ulcer disregarded?].

    PubMed

    Zaugg, Patrice; Koch, Nathalie; Erba, Paolo; Raffoul, Wassim

    2016-02-10

    We report the case of a 65years old patient followed for more than 4 years for a leg ulcer in whom a rare combination of pyoderma gangrenosum with breast cancer was diagnosed. This is a rare skin disease, usually associated with systemic disease: digestive, rheumatological or malignant. The diagnosis is mainly clinical. Taking patient diagnostic management has two objectives: to eliminate other causes of skin ulcer and determine whether there is a concomitant illness that can be treated. Bacteriological swab and a biopsy should always be performed. The treatment consists of topical corticosteroids and systemic therapy with corticosteroids or immunosuppressive agents. PMID:27039446

  4. Pyoderma gangrenosum, rare parietal complication after colorectal surgery.

    PubMed

    Miron, A; Giulea, C; Tudose, I; Petrache, D; Giurcaneanu, C

    2014-01-01

    Pyoderma gangrenosum (PG) is a rare chronic destructive inflammatory skin disease characterized by the presence of nodules and pustules with progressively enlarging ulcers and orcutaneous necrosis. In most cases PG is idiopathic, but sometimes it is associated with conditions that often have vasculitis, such as gammapathies, inflammatory bowel diseases or chronic arthritis. PG is neither infectious nor gangrenous,but some authors advanced the theory that an infectious etiology (streptococci and staphylococci) could be incriminated.Recently, there are reports in the literature stating that PG is a condition that can occur after local trauma, especially surgery.We report the case of a 73 year old man who presented himself to the Surgery Department with rectal adenocarcinoma and postoperatively developed well-demarcated, vegetative plaques,ranging from 2 to 5 cm in diameter, with central ulceration associated with necrosis and a purulent secretion, delimitated by raised, dusky erythematous borders. These lesions were located on the abdomen and it is important to mention that the injuries occurred at the site of surgical stitches used during the rectum amputation surgery, with no other anatomical locations,pruritus or pain associated. We performed two different histopathological examinations for this patient, regarding the rectal specimens and the cutaneous specimen. The first examinations revealed rectal adenocarcinoma and nonspecific colitis. The second examination was concluded with the diagnosis of pyoderma gangrenosum, the ulcerative stage. The patient had a very good clinical response to systemic steroid therapy. PMID:24742420

  5. [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. PMID:25672810

  6. Use of Becaplermin for nondiabetic ulcers: pyoderma gangrenosum and calciphylaxis

    PubMed Central

    Twu, Olivia; Mednik, Suzanne; Scumpia, Philip; Doaty, Sarah; Worswick, Scott

    2015-01-01

    Large difficult to heal ulcers of various etiologies carry a high morbidity and mortality rate. Becaplermin is a recombinant platelet-derived growth factor approved for treatment of diabetic ulcers. In this two-case series, we report the use of becaplermin in the treatment of ulcers due to (i) calciphylaxis, an often fatal condition resulting from systemic calcification and thrombosis of vessels and (ii) pyoderma gangrenosum (PG), a neutrophilic dermatosis. We also report that topical collagenase worsened PG ulcers, consistent with pathergy. Becaplermin can be used to help treat ulcers resulting from calciphylaxis and PG. These encouraging results lend support for the utilization of becaplermin in the treatment of nondiabetic chronic ulcers of various etiologies. PMID:26556220

  7. Use of Becaplermin for nondiabetic ulcers: pyoderma gangrenosum and calciphylaxis.

    PubMed

    Twu, Olivia; Mednik, Suzanne; Scumpia, Philip; Doaty, Sarah; Worswick, Scott

    2016-03-01

    Large difficult to heal ulcers of various etiologies carry a high morbidity and mortality rate. Becaplermin is a recombinant platelet-derived growth factor approved for treatment of diabetic ulcers. In this two-case series, we report the use of becaplermin in the treatment of ulcers due to (i) calciphylaxis, an often fatal condition resulting from systemic calcification and thrombosis of vessels and (ii) pyoderma gangrenosum (PG), a neutrophilic dermatosis. We also report that topical collagenase worsened PG ulcers, consistent with pathergy. Becaplermin can be used to help treat ulcers resulting from calciphylaxis and PG. These encouraging results lend support for the utilization of becaplermin in the treatment of nondiabetic chronic ulcers of various etiologies. PMID:26556220

  8. Successful vaginal birth after prior cesarean section in a patient with pyoderma gangrenosum.

    PubMed

    Park, Jee Yoon; Lee, JoonHo; Park, Joong Shin; Jun, Jong Kwan

    2016-01-01

    Pyoderma gangrenosum is an extremely rare chronic cutaneous disease causing severe ulceration. It can be developed after minor trauma or surgical procedure. The typical features mimic acute infection site, however the treatment methods are opposing since pyoderma gangrenosum is improved with the use of corticosteroids, not antibiotic therapy. We here report a patient who had been diagnosed for acute infection after cesarean delivery in 2011 and treated with a number of antibiotics, but failed to recover. The patient had suffered from pain of the disease and also renal failure caused by antibiotics. Ultimately she had been diagnosed as pyoderma gangrenosum and managed successfully with steroids. For her next pregnancy in 2013, we tried vaginal delivery after prior cesarean section and it was uneventful during and after delivery. PMID:26866039

  9. Successful vaginal birth after prior cesarean section in a patient with pyoderma gangrenosum

    PubMed Central

    Park, Jee Yoon; Lee, JoonHo; Park, Joong Shin

    2016-01-01

    Pyoderma gangrenosum is an extremely rare chronic cutaneous disease causing severe ulceration. It can be developed after minor trauma or surgical procedure. The typical features mimic acute infection site, however the treatment methods are opposing since pyoderma gangrenosum is improved with the use of corticosteroids, not antibiotic therapy. We here report a patient who had been diagnosed for acute infection after cesarean delivery in 2011 and treated with a number of antibiotics, but failed to recover. The patient had suffered from pain of the disease and also renal failure caused by antibiotics. Ultimately she had been diagnosed as pyoderma gangrenosum and managed successfully with steroids. For her next pregnancy in 2013, we tried vaginal delivery after prior cesarean section and it was uneventful during and after delivery. PMID:26866039

  10. Pyoderma gangrenosum in an abdominal surgical site: a case report.

    PubMed

    Ogata, Kenichi; Takamori, Hiroshi; Ikuta, Yoshiaki; Tanaka, Hideyuki; Ozaki, Nobuyuki; Hayashi, Hiromitsu; Ogawa, Katsuhiro; Doi, Koichi

    2015-12-01

    Pyoderma gangrenosum (PG) is an uncommon, ulcerative skin disease that is often associated with systemic diseases. Herein, we report a development of PG in a surgical site after cholecystectomy that was difficult to discriminate from surgical site infection. The patient was a 74-year-old man who had previously been diagnosed with myelodysplastic syndrome (MDS). Laparoscopic cholecystectomy was planned under diagnosis of cholecystolithiasis, but we converted to open cholecystectomy. The surgical wound was partially erythematous 4 days after surgery. In spite of opening the wound, cleansing it with sterile saline, and administration of antibiotics, inflammation spread with erosion. The clinical manifestations and histopathologic features of biopsy specimen indicated that diagnosis of PG associated with MDS was most likely. Administration of glucocorticoids made a rapid response of skin inflammation. The differential diagnosis of postoperative wound healing complications that were unresponsive to conventional wound local care and antibiotic therapy should include PG, especially in patients with systemic diseases such as MDS. PMID:26943446

  11. 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. PMID:26047254

  12. Recalcitrant pyoderma gangrenosum--two cases successfully treated with cyclosporin A.

    PubMed

    Kavanagh, G M; Ross, J S; Cronin, E; Smith, N P; Black, M M

    1992-01-01

    The successful use of cyclosporin A (CSA) in organ transplantation is now well established. In recent years its usefulness has extended to the treatment of cutaneous autoimmune disorders, including pyoderma gangrenosum (P.G.). We report two further cases of recalcitrant P.G., both associated with rheumatoid arthritis (R.A.) which responded to low dose CSA. PMID:1424262

  13. Perianal pyoderma gangrenosum after excision and fulguration of anal condyloma acuminatum

    PubMed Central

    Agnew, Jennifer L.; Strombom, Paul D.; Fong, Carmen F.; Kelly, Timothy J.; Martz, Joseph E.

    2015-01-01

    Introduction Pyoderma gangrenosum (PG) is a rare, inflammatory skin pathology frequently associated with systemic inflammatory disease. While rare after surgery, recognition of this disease in the post-surgical setting is important as it can mimic wound infection. Presentation of case We herein present a dramatic presentation of perianal PG four days after routine excision and fulguration of anal condyloma acuminatum. The affected area did not improve with broad spectrum antibiotics or surgical debridement. A diagnosis of PG was made from clinical suspicion and pathology findings, and further confirmed with rapid improvement after starting steroids. Diagnosis of this disease in the postoperative period requires high suspicion when the characteristic ulcerative or bullae lesions are seen diffusely and show minimal improvement with antibiotic treatment or debridement. Discussion Our case highlights the importance of recognizing this disease in the post-operative period, to allow for early initiation of appropriate treatment and prevent unnecessary surgical debridement of a highly sensitive area. There have been 32 case reports of PG in the colorectal literature, mostly following stoma creation. There is one case report of idiopathic perianal pyoderma gangrenosum with no known prior trauma. To our knowledge there are no previously reported cases of perianal PG after routine elective anorectal surgery. Conclusion This is the first reported case of perianal pyoderma gangrenosum in the post-surgical setting. Increased awareness of pyoderma gangrenosum in the surgical literature will aid in prompt diagnosis and proper medical management of this uncommon postoperative morbidity. PMID:26547888

  14. 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. PMID:23188209

  15. 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. PMID:24986043

  16. A case of surgically treated peristomal pyoderma gangrenosum in a patient with rheumatoid arthritis.

    PubMed

    Khajehnoori, Masoomeh; O'Brien, Tim

    2016-01-01

    Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is difficult to diagnose and treat. It is characterized by the rapid progression of painful necrotic ulcer surrounding an area of abdominal stoma. It is almost exclusively associated with inflammatory bowel disease even after bowel surgery and is associated with significant morbidity. Diagnosis of pyoderma gangrenosum is based on exclusion of other disorders replicating some of its clinical features and histopathological evidence.This is a case report of a 56-year-old lady with rheumatoid arthritis who presented with rapidly progressing abdominal ulcer 8 months after a Hartmanns procedure for perforated diverticulitis. The ulcer had formed a large cavity causing faecal filling in the dependent defect. The other causes of ulcer were excluded with negative histopathology, negative polymerase chain reaction for Mycobacterium ulcerans and negative acid fast bacillus (AFB) test. She was diagnosed with PPG which is routinely treated medically due to risk of setting off a second focus of pyoderma if surgically intervened. However due to increased risk of faecal peritonitis, it was decided to proceed with surgical debridement. This article will discuss the case in more detail and briefly discuss diagnosis and treatment options for PPG. PMID:27302499

  17. A case of surgically treated peristomal pyoderma gangrenosum in a patient with rheumatoid arthritis

    PubMed Central

    Khajehnoori, Masoomeh; O'Brien, Tim

    2016-01-01

    Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is difficult to diagnose and treat. It is characterized by the rapid progression of painful necrotic ulcer surrounding an area of abdominal stoma. It is almost exclusively associated with inflammatory bowel disease even after bowel surgery and is associated with significant morbidity. Diagnosis of pyoderma gangrenosum is based on exclusion of other disorders replicating some of its clinical features and histopathological evidence. This is a case report of a 56-year-old lady with rheumatoid arthritis who presented with rapidly progressing abdominal ulcer 8 months after a Hartmanns procedure for perforated diverticulitis. The ulcer had formed a large cavity causing faecal filling in the dependent defect. The other causes of ulcer were excluded with negative histopathology, negative polymerase chain reaction for Mycobacterium ulcerans and negative acid fast bacillus (AFB) test. She was diagnosed with PPG which is routinely treated medically due to risk of setting off a second focus of pyoderma if surgically intervened. However due to increased risk of faecal peritonitis, it was decided to proceed with surgical debridement. This article will discuss the case in more detail and briefly discuss diagnosis and treatment options for PPG. PMID:27302499

  18. Leech Induced Pyoderma Gangrenosum in an Ulcerative Colitis Patient: A Case Report.

    PubMed

    Sadeghi, Anahita; Navabakhsh, Behrouz; Izadi Vahedi, Niloofar

    2016-01-01

    Pyoderma gangrenosum (PG) is a painful skin lesion that results from excessive inflammatory response to a host of traumatic, inflammatory, or neoplastic processes in susceptible individuals. A clear pathogenetic mechanism as well as an exhaustive list of potential triggers for PG is yet to be fully characterized. This case documents the occurrence of pyoderma gangrenosum following leech-therapy in a patient who is a known case of ulcerative colitis and it deserves attention because leeches have been part of medical armamentarium since ancient times and have re-emerged in the last century relying on their ancient charm and modern research revealing potential benefits of several bioactive substances in their saliva. PMID:26933484

  19. Leech Induced Pyoderma Gangrenosum in an Ulcerative Colitis Patient: A Case Report

    PubMed Central

    Sadeghi, Anahita; Navabakhsh, Behrouz; Izadi Vahedi, Niloofar

    2016-01-01

    Pyoderma gangrenosum (PG) is a painful skin lesion that results from excessive inflammatory response to a host of traumatic, inflammatory, or neoplastic processes in susceptible individuals. A clear pathogenetic mechanism as well as an exhaustive list of potential triggers for PG is yet to be fully characterized. This case documents the occurrence of pyoderma gangrenosum following leech-therapy in a patient who is a known case of ulcerative colitis and it deserves attention because leeches have been part of medical armamentarium since ancient times and have re-emerged in the last century relying on their ancient charm and modern research revealing potential benefits of several bioactive substances in their saliva. PMID:26933484

  20. Pyoderma gangrenosum in association with Janus kinase 2 (JAK2V617F) mutation.

    PubMed

    Palanivel, J A; Macbeth, A E; Levell, N J

    2013-01-01

    Pyoderma gangrenosum (PG) commonly occurs in association with various haematological and inflammatory disorders. We report a new association, a Janus kinase (JAK)2 mutation, in a 63-year-old patient with PG. We hypothesise that PG occurs by direct activation of JAK along with signal transducers and activators of transcription (STAT), a common mechanism involved in the pathogenesis of inflammatory and haematological diseases. PMID:22607468

  1. Granulomatous pyoderma gangrenosum of the genitalia in the absence of Crohn's disease

    PubMed Central

    Kambil, Srinath M.; Bhat, Ramesh M.; Dandekeri, Sukumar

    2015-01-01

    Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic disorder of the skin. Atypical variants of PG such as vegetative PG, bullous PG, and pustular forms are described in literature. Occasionally, granulomatous reaction in dermis may be seen on histology when PG is associated with Crohn's disease or in the vegetative variant of PG. We report a case of granulomatous PG involving the genitalia in a 43-year-old female without associated inflammatory bowel disease. PMID:26392658

  2. Pyoderma gangrenosum in association with erythema elevatum diutinum: report of two cases.

    PubMed

    Planagumà, M; Puig, L; Alomar, A; Matías-Guiu, X; de Moragas, J M

    1992-03-01

    We report on the appearance of centrifugally spreading ulcers with undermined borders in two patients with chronic recurrent erythema elevatum diutinum controlled with dapsone. The ulcerated lesions were consistent on clinical and pathologic examination with the diagnosis of pyoderma gangrenosum. They eventually responded to treatment with oral corticosteroids. The addition of cyclosporine was required in one case. No associated disease was found in any of the patients. The possible pathophysiological mechanisms of this uncommon association are reviewed. PMID:1572226

  3. [Pyoderma gangrenosum of the penis presenting as Fournier's gangrene: a case report].

    PubMed

    Kohjimoto, Yasuo; Inagaki, Takeshi; Iba, Akinori; Kikkawa, Kazuro; Suzuki, Atsushi; Uekado, Yasunari; Shinka, Toshiaki

    2005-06-01

    We report a case of pyoderma gangrenosum of the penis presenting as Fournier's gangrene. A 77-year-old man who had undergone radiotherapy for localized prostate cancer 16 month earlier, presented with penile pain and fever. Symptoms began with erythema and induration on the dorsal surface of the penile shaft followed by spontaneous purulent drainage with severe pain. Magnetic resonance imaging was unremarkable except for swelling of the penile skin. Biopsy of the ulcerative penile lesion demonstrated a nonspecific inflammation without vasculitis or malignancy. Despite broad-spectrum antibiotics and debridement, the penile lesion extended and new satellite lesions developed as pustules on the glans. Since cultures were negative for aerobic and anaerobic bacteria, a course of intravenous prednisolone was then initiated at 100 mg/day. Within 24 hours the temperature normalized, progression of the penile lesions stopped and became convalescent. The steroid was then tapered and discontinued. The penile lesions healed slowly during the subsequent 1-month period. Based on the clinical course and histopathological findings as well as exclusion of other ulcerative conditions, a diagnosis of pyoderma gangrenosum was made. Penile involvement of this non-infectious ulcerating skin disease has rarely been reported. Pyoderma gangrenosum affecting the penile skin, such as that in present case, may show a similar presentation as Fournier's gangrene. Prompt differential diagnosis is mandatory since effective management for each processes is markedly different. PMID:16050483

  4. [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. PMID:26699892

  5. Gauze-based negative pressure wound therapy: a valid method to manage pyoderma gangrenosum.

    PubMed

    Fraccalvieri, Marco; Fierro, Maria Teresa; Salomone, Marco; Fava, Paolo; Zingarelli, Enrico M; Cavaliere, Giovanni; Bernengo, Maria G; Bruschi, Stefano

    2014-04-01

    Pyoderma gangrenosum (PG) is an uncommon ulcerative, non-infective chronic inflammatory skin disorder of unknown aetiology. Systemic therapies are necessary to control the associated medical diseases, and, due to the inflammatory nature of PG, topical or systemic immunosuppressant agents are effective, but wound healing is usually slow. Negative wound pressure therapy (NPWT) has become an important tool for the management of complex skin ulcers, and usage in PG has been recently described in the literature: we present four cases of classic PG in which NPWT in association with systemic therapy achieved wound healing and a drastic pain reduction. PMID:22891652

  6. Pyoderma gangrenosum with an underlying ulcerative colitis associated with bone tuberculosis

    PubMed Central

    Patvekar, Milind A.; Virmani, Neha C.

    2013-01-01

    Pyoderma gangrenosum is a rare noninfective neutrophilic dermatosis, characterized by progressive painful ulceration. It is frequently associated with systemic disorders like inflammatory bowel disease, rheumatoid arthritis and myeloproliferative diseases. However, its association with infectious diseases in particular with tuberculosis is extremely rare. Diagnosis is based on the history of an underlying disease, a typical clinical presentation, histopathology and exclusion of other diseases leading to ulcerations of similar appearance. Immunosuppression with corticosteroids remains the mainstay of treatment. We report a case of a 49-year-old male with long-standing ulcerative colitis, associated with tuberculosis of hip, who presented with nonhealing ulcers over the lower extremity. PMID:23440150

  7. The adverse consequences of pyoderma gangrenosum in a 13 year old child

    PubMed Central

    Lambropoulos, Vassilis; Patsatsi, Aikaterini; Tsona, Afroditi; Papakonstantinou, Antonios; Filippopoulos, Antonios; Sotiriadis, Dimitrios

    2011-01-01

    Introduction Pyoderma gangrenosum (PG) is an uncommon, but serious, non infectious, neutrophilic dermatosis that causes cutaneous necrosis with a characteristically rapid evolution. Presentation of case A 13 year-old girl was admitted with a postoperative infected wound, which was surgically debrided. A new more aggressive lesion on the left upper extremity led the patient to the intensive care unit. Clinical diagnosis of pyoderma gangrenosum was introduced with a crucial delay. An immediate clinical improvement after immunosuppressive therapy with systemic corticosteroids and cyclosporine was observed. The extensive cutaneous deficits were covered with keratinocyte cultured cells with an aesthetically good outcome. Discussion Diagnosis of PG in young children is very difficult, especially without dermatological evaluation. This deforming ulcerative skin disease is probably a result of altered immunologic reactivity. Its early recognition may prevent unnecessary surgical treatment which leads to dangerous complications. Conclusion To our knowledge this is the first case of PG with such a widespread distribution reported in a child, as a consequence of iatrogenic pathergy. PMID:22096733

  8. Pyoderma gangrenosum and Wegener granulomatosis-like syndrome induced by cocaine.

    PubMed

    Jiménez-Gallo, D; Albarrán-Planelles, C; Linares-Barrios, M; Rodríguez-Hernández, C; Martínez-Rodríguez, A; García-Moreno, E; Bravo-Monge, R

    2013-12-01

    Cocaine abuse is associated with various skin and rheumatological diseases that mimic primary autoimmune diseases, including retiform purpura with involvement of the ears, cocaine-induced midline destructive lesions (CIMDL), and eruptive pyoderma gangrenosum (PG). Previous reports have suggested the use of perinuclear antineutrophil cytoplasmic antibodies (pANCA) with specificity against human neutrophil elastase (HNE) to differentiate these cocaine-induced diseases from primary autoimmune diseases. We describe a case of a 54-year-old woman with a history of cocaine abuse, who had PG lesions on her legs with accompanying CIMDL and lung lesions similar to those seen in Wegener granulomatosis. Detection of HNE-positive pANCA, and improvement or clinical recurrence after cessation or consumption of cocaine, respectively, were key to differentiating this presentation from primary autoimmune disease. PMID:24252079

  9. 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

  10. Pyoderma Gangrenosum Mimicking an Infected Wound following Dynamic Hip Screw Fixation

    PubMed Central

    Nizamoglu, Metin

    2015-01-01

    Pyoderma gangrenosum (PG) is an inflammatory ulcerative neutrophilic dermatosis that can occur following skin trauma. The correct diagnosis is not often made immediately as the condition can mimic an infective appearance. This leads to delays in the appropriate management of high dose steroids. Although debridement can offer aid in resolving lesions, this is contraindicated in the acute phase as this can cause acceleration of the pathogenic process. Biopsy of the lesion does not offer a definitive diagnosis; therefore suspicion must be maintained as the diagnosis is ultimately a clinical one. Any postoperative pustular ulcerative lesion not improving despite antibiotic therapy that also yields negative bacteriological and fungal studies should lead to consideration of this diagnosis. We document the first case of PG developing following intertrochanteric femur fracture fixation using dynamic hip screw. PMID:26380139

  11. Juvenile gangrenous vasculitis of the scrotum: Is it a variant of pyoderma gangrenosum?

    PubMed

    Caputo, Ruggero; Marzano, Angelo V; Di Benedetto, Alessandra; Ramoni, Stefano; Cambiaghi, Stefano

    2006-08-01

    Juvenile gangrenous vasculitis of the scrotum was described by Piñol et al in 1974 as a unique variant of scrotal gangrene of unknown origin, occurring exclusively in young individuals. It was characterized by an acute onset of skin ulcers undergoing complete resolution after appropriate therapy, with no relapses. We present a typical case of this extremely rare disease affecting a 16-year-old boy in whom the scrotal ulcerations were preceded by an episode of pharyngitis with fever. The condition promptly regressed after administration of intramuscular betamethasone in combination with oral ciprofloxacin. According to Piñol et al, juvenile gangrenous vasculitis of the scrotum, although poorly known to dermatologists, should be regarded as a distinctive entity within the wide group of scrotal gangrenes. On the other hand, the hypothesis that this condition may well represent a variant of pyoderma gangrenosum is discussed. PMID:16843125

  12. Refractory postsurgical pyoderma gangrenosum in a patient with Beckwith Wiedemann syndrome: response to multimodal therapy

    PubMed Central

    Fakhar, Faiza; Memon, Sehrish; Deitz, Diane; Abramowitz, Richard; Alpert, Deborah R

    2013-01-01

    Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be difficult to diagnose and treat. We presented a 41-year-old woman who required skin grafting following third-degree burns to her left breast. She suffered recurrent graft dehiscence and infections over many years, prompting elective bilateral reduction mammoplasty. She subsequently developed suture margin ulcerations unresponsive to topical therapies and antibiotics. Skin biopsies were non-specific, and a clinical diagnosis of PG was established. Although initially responsive to corticosteroids, wounds promptly recurred following steroid taper. She was treated unsuccessfully with various immunomodulatory agents and underwent elective bilateral mastectomy. Following a mastectomy, she developed progressive deep chest wall ulcerations. She failed numerous immunomodulatory treatments, surgical wound closure and negative pressure wound therapy. Ultimately, treatment with adalimumab, mycophenolate mofetil and prednisone, in addition to hyperbaric oxygen therapy facilitated progressive healing. Our case highlights the role of collaborative multimodal therapy for the treatment of refractory PG. PMID:24154999

  13. Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn's disease.

    PubMed

    Hurabielle, Charlotte; Schneider, Pierre; Baudry, Clotilde; Bagot, Martine; Allez, Matthieu; Viguier, Manuelle

    2016-01-01

    Systemic steroids, in association or not with cyclosporin, are indicated for the treatment of large or widespread Pyoderma gangrenosum (PG). We report the case of a 27-year-old woman with a 15-year history of severe Crohn's disease, who developed a severe and disseminated PG, refractory to multiple lines of treatment. Infliximab and adalimumab were contraindicated, either because of allergy or of ineffectiveness on Crohn's disease. The addition of certolizumab pegol to the baseline treatment, associating systemic steroids and tacrolimus, finally allowed the complete healing of PG. Oral prednisone was stopped and tacrolimus was decreased, without any cutaneous or digestive relapse. Certolizumab pegol could be an alternative therapy in the treatment of PG in case of intolerance or ineffectiveness of the other anti-tumor necrosis factor (anti-TNF) therapies. PMID:25909366

  14. Pyoderma gangrenosum and pregnancy: an example of abnormal inflammation and challenging treatment.

    PubMed

    Steele, R B; Nugent, W H; Braswell, S F; Frisch, S; Ferrell, J; Ortega-Loayza, A G

    2016-01-01

    Pyoderma gangrenosum (PG) is a neutrophil-predominant inflammatory disease that initially presents as a sterile pustule and may progress to ulcerations. Its root cause is unknown, but the presentation is commonly associated with systemic inflammatory conditions such as inflammatory bowel disease, arthritis and haematological abnormalities. On the other hand, pregnant women show a progressive neutrophilia during gestation, which culminates in a major inflammatory event to help drive labour. Although uncommonly, PG has been associated with pregnancy, which provides an additional link to systemic inflammation as an underlying cause of PG. We reviewed documented presentations of PG in gravid and post-partum patients, and have speculated on the possible pathogenesis based on their clinical presentations. Also, we summarize the reported treatments and their outcomes in these patients. PMID:26474193

  15. Pyoderma gangrenosum of articulations carpi associated with ulcerative colitis: one case report

    PubMed Central

    Meng, Xia; Zhu, Xinying; Chen, Liping; Wu, Jing; Liu, Gaifang; Xia, Bing

    2015-01-01

    Pyoderma gangrenosum (PG), an extra-intestinal manifestation of ulcerative colitis (UC), is extremely rare. Up to now, there is no any data reported the occurrence of PG in joints, especially in China. The management of PG associated with UC is a therapeutic challenge. Our report here showed that a female patient diagnosed as UC complained a pustule in the dorsal side of left wrist, primarily was diagnosed as bone tuberculosis. The pustule progressed rapidly into a severe painful necrolytic cutaneous ulcer with a pale purple irregular destructive ulcer edge, this patient was diagnosed by UC complicated with PG, and skin lesions were cured by UC treatment. Here, we for the first time present a case acquired correct diagnosis and successful treatment of UC associated with PG of articulations carpi. We report this case here in order to provide more information about this disease to more doctors, furthermore, to decrease the rates of misdiagnosis and missed diagnosis. PMID:26770554

  16. Idiopathic Pyoderma Gangrenosum as a Novel Manifestation of the HIV Immune Reconstitution Inflammatory Syndrome: A Report of Three Cases.

    PubMed

    Nambudiri, Vinod E; Kersellius, Romona; Harp, Joanna; Maniar, J K; Maurer, Toby A

    2015-07-01

    The initiation of antiretroviral treatment for individuals with HIV may be accompanied by a paradoxical flare of underlying inflammatory diseases, the recurrence of dormant infections, or worsening of prior treated opportunistic infections, termed the immune reconstitution inflammatory syndrome (IRIS). Cutaneous manifestations of IRIS are common. Pyoderma gangrenosum is a neutrophilic dermatosis postulated to reflect disrupted innate immune regulation causing altered neutrophil chemotaxis. It is uncommonly reported in association with HIV. In this case series, we present three cases of IRIS manifesting with pyoderma gangrenosum in individuals with HIV from India and the United States to raise awareness of this previously undescribed presentation and discuss the treatment challenges in the management of these patients. PMID:26731836

  17. Treatment of refractory Crohn's disease and pyoderma gangrenosum with a combination regimen of rifaximin, gentamicin and metronidazole.

    PubMed

    Goldberg, Neil D; Vadlamudi, Aravinda; Parrish, Nicole

    2015-01-01

    The etiology of Crohn's disease (CD) remains controversial. It is hypothesized that CD is the result of an abnormal immune response to the gut flora in genetically susceptible hosts. However, an infectious etiology has not been completely ruled out. Antibiotics have been utilized with some success to modify the course of the disease. Here, we report a patient with CD and pyoderma gangrenosum refractory to standard therapy, including biologics, who achieved remission with a combination of rifaximin, gentamicin and metronidazole. PMID:25802494

  18. Treatment of Refractory Crohn's Disease and Pyoderma Gangrenosum with a Combination Regimen of Rifaximin, Gentamicin and Metronidazole

    PubMed Central

    Goldberg, Neil D.; Vadlamudi, Aravinda; Parrish, Nicole

    2015-01-01

    The etiology of Crohn's disease (CD) remains controversial. It is hypothesized that CD is the result of an abnormal immune response to the gut flora in genetically susceptible hosts. However, an infectious etiology has not been completely ruled out. Antibiotics have been utilized with some success to modify the course of the disease. Here, we report a patient with CD and pyoderma gangrenosum refractory to standard therapy, including biologics, who achieved remission with a combination of rifaximin, gentamicin and metronidazole. PMID:25802494

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

    PubMed

    2015-02-01

    [In the article "Association of Pyoderma Gangrenosum, Acne, and Suppurative Hidradenitis (PASH) Shares Genetic and Cytokine Profiles With Other Autoinflammatory Diseases", which appeared in Volume 93, Issue 27 of Medicine, one of Orietta M. Borghi's affiliations was omitted. The article should have stated that Orietta M. Borghi is associated with the IRCCS Istituto Auxologico Italiano, Milano, Italy as well as the Dipartimento di Scienze Cliniche e di Comunità, Università di Milano.]. PMID:25803365

  20. [Pseudo-septicemic pyoderma gangrenosum and breast cancer. Apropos of a case caused by an intramuscular injection].

    PubMed

    Maigre, M; Bouachour, G; Varache, N; Alquier, P; Verret, J L

    1991-01-01

    We report a case of pyoderma gangrenosum (PG) mimicking a severe infectious skin disease in a woman with metastatic breast cancer. PG started at the site of an intramuscular injection administered a few days previously, and it subsequently extended. The skin disease was cured by high-dose corticosteroid therapy and clofazimine, but it marked a turn for the worst in the course of the breast cancer which became rapidly fatal. PMID:1792438

  1. Hyperbaric Oxygen Therapy for the Adjunctive Treatment of Pyoderma Gangrenosum: A Case Report.

    PubMed

    Chiang, I-Han; Liao, Yi-Shu; Dai, Niann-Tzyy; Chiao, Hao-Yu; Chou, Chang-Yi; Chen, Shyi-Gen; Chen, Tim-Mo; Chang, Shun-Cheng

    2016-05-01

    Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by an ulcerative skin condition and confirmed through a diagnosis of exclusion. Management usually consists of systemic drug therapy, such as corticosteroids, sulfones, or immunosuppressants, either alone or in combination. Long-term use of these medications often has untold side effects. Hyperbaric oxygen therapy (HBOT) has been shown effective in the treatment of PG, reducing pain and tempering the need for medication. A case is presented of a 54-year-old woman with diabetes, hypertension, and a peptic ulcer who presented with painful, purulent ulcers on her buttocks, hands, and lower extremities of 2 weeks' duration. She was ultimately diagnosed with PG and provided 20 mg/day of oral prednisone for 1 week, tapered to 10 mg/day in the next week and then stopped. In addition, she received 12 sessions of HBOT - she breathed in 100% oxygen under 2.5 atmospheres absolute pressure for 90 minutes over 2 weeks. Her wounds healed without scarring. This excellent outcome including good wound healing, decreased pain, and reduced doses of systemic corticosteroids warrants additional study of the adjunctive use of HBOT for PG. PMID:27192719

  2. 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. PMID:23171584

  3. Multiple pulmonary cavitary nodules with pyoderma gangrenosum in patient with rheumatoid arthritis.

    PubMed

    Be, Miae; Cha, Hee Jeong; Park, Chanho; Park, Yongtae; Jung, Hwasik; Lee, Yoeunim; Jegal, Yangjin

    2016-01-01

    Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic disorder of skin. Its pulmonary manifestations are uncommon and only less than forty cases have been reported in the literature previously. PG is associated with variable systemic diseases, most commonly inflammatory bowel disease and hematologic malignancies. It reported rarely in rheumatoid arthritis (RA). We report a case of PG lung involvement in patient with RA associated interstitial lung disease. A 66-year-old woman presented with productive cough and recurrent ulcerative lesion on her left ankle. She had a 15-year history of RA associated interstitial lung disease and treated with methotrexate, sulfasalazine, hydroxychloroquine and methylprednisolone. On physical examination, there were a few tender, erythematous subcutaneous nodules ranging from 1 to 3 cm in diameter on her left thigh and left elbow. Anti-neutrophil cytoplasmic antibodies (ANCAs) are negative. Her chest CT scan demonstrated multifocal cavitary consolidations on the background of reticular opacity and honeycombing. Punch biopsy of erythematous nodule on thigh showed neutrophilic abscess with necrotic debris. The skin and lung lesions were rapidly improved with 0.5 mg/kg/day of prednisolone. PMID:26889492

  4. Multiple pulmonary cavitary nodules with pyoderma gangrenosum in patient with rheumatoid arthritis

    PubMed Central

    Be, Miae; Cha, Hee Jeong; Park, Chanho; Park, Yongtae; Jung, Hwasik; Lee, Yoeunim

    2016-01-01

    Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic disorder of skin. Its pulmonary manifestations are uncommon and only less than forty cases have been reported in the literature previously. PG is associated with variable systemic diseases, most commonly inflammatory bowel disease and hematologic malignancies. It reported rarely in rheumatoid arthritis (RA). We report a case of PG lung involvement in patient with RA associated interstitial lung disease. A 66-year-old woman presented with productive cough and recurrent ulcerative lesion on her left ankle. She had a 15-year history of RA associated interstitial lung disease and treated with methotrexate, sulfasalazine, hydroxychloroquine and methylprednisolone. On physical examination, there were a few tender, erythematous subcutaneous nodules ranging from 1 to 3 cm in diameter on her left thigh and left elbow. Anti-neutrophil cytoplasmic antibodies (ANCAs) are negative. Her chest CT scan demonstrated multifocal cavitary consolidations on the background of reticular opacity and honeycombing. Punch biopsy of erythematous nodule on thigh showed neutrophilic abscess with necrotic debris. The skin and lung lesions were rapidly improved with 0.5 mg/kg/day of prednisolone. PMID:26889492

  5. Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome case

    PubMed Central

    Malkan, Umit Yavuz; Gunes, Gursel; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin

    2016-01-01

    Thalidomide may be used as a treatment option for pyoderma gangrenosum (PG) and myelodysplastic syndrome (MDS). Herein, we aimed to report a patient who was treated well with thalidomide and whose diagnosis was PG with MDS. A 61-year-old man with painless ecchymotic lesions in his right upper extremity was admitted to the hospital in Isparta, Turkey, in January 2015. The lesions were diagnosed as PG. In his anamnesis, it was found that he was diagnosed with MDS 6 years ago and had been treated with cyclosporine at 2×100 mg for 5 years, which was stopped in January 2015. Aspiration from liver lesion revealed the presence of Mycobacterium tuberculosis, so antituberculosis treatment was started. Bone marrow investigation revealed MDS-refractory anemia with excess blasts (7%). For lesions in bilateral upper extremities, thalidomide treatment was started at 50 mg/d. After 1 month from the initiation of thalidomide treatment, the lesions in upper extremities had disappeared. In the literature, there are some reports of patients with PG who were successfully treated with thalidomide. Our patient is a complicated case who simultaneously has MDS, PG, and tuberculosis infection. The reason for thalidomide usage in our patient was the need of immune modulation without immune suppression. Our patient has tolerated the drug well, and excellent response was obtained after 1 month of initiation of thalidomide treatment. To conclude, thalidomide is a very effective drug acting as an immune modulator, which is useful in the clinical management of both MDS and PG. PMID:27051318

  6. Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome case.

    PubMed

    Malkan, Umit Yavuz; Gunes, Gursel; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin

    2016-01-01

    Thalidomide may be used as a treatment option for pyoderma gangrenosum (PG) and myelodysplastic syndrome (MDS). Herein, we aimed to report a patient who was treated well with thalidomide and whose diagnosis was PG with MDS. A 61-year-old man with painless ecchymotic lesions in his right upper extremity was admitted to the hospital in Isparta, Turkey, in January 2015. The lesions were diagnosed as PG. In his anamnesis, it was found that he was diagnosed with MDS 6 years ago and had been treated with cyclosporine at 2×100 mg for 5 years, which was stopped in January 2015. Aspiration from liver lesion revealed the presence of Mycobacterium tuberculosis, so antituberculosis treatment was started. Bone marrow investigation revealed MDS-refractory anemia with excess blasts (7%). For lesions in bilateral upper extremities, thalidomide treatment was started at 50 mg/d. After 1 month from the initiation of thalidomide treatment, the lesions in upper extremities had disappeared. In the literature, there are some reports of patients with PG who were successfully treated with thalidomide. Our patient is a complicated case who simultaneously has MDS, PG, and tuberculosis infection. The reason for thalidomide usage in our patient was the need of immune modulation without immune suppression. Our patient has tolerated the drug well, and excellent response was obtained after 1 month of initiation of thalidomide treatment. To conclude, thalidomide is a very effective drug acting as an immune modulator, which is useful in the clinical management of both MDS and PG. PMID:27051318

  7. 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. PMID:26470620

  8. Complete resolution of non-necrotizing lung granuloma and pyoderma gangrenosum after restorative proctocolectomy in a woman with severe ulcerative colitis and cytomegalovirus infection.

    PubMed

    Sartini, Alessandro; Bianchini, Marcello; Schepis, Filippo; Marzi, Luca; De Maria, Nicola; Villa, Erica

    2016-02-01

    Here, we report the unusual case of an ulcerative colitis female patient presenting together with cytomegalovirus infection, pyoderma gangrenosum and a noncaseating lung granuloma, both resistant to immunomodulatory drugs which dramatically obtained a clinical stable remission after restorative proctocolectomy. PMID:26862424

  9. 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. PMID:25876705

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

    PubMed Central

    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. PMID:26327988

  11. Generalized Pyoderma Gangrenosum Associated with Ulcerative Colitis: Successful Treatment with Infliximab and Azathioprine.

    PubMed

    Chatzinasiou, Foteini; Polymeros, Dimitrios; Panagiotou, Maro; Theodoropoulos, Konstadinos; Rigopoulos, Dimitrios

    2016-04-01

    Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, part of the spectrum of neutrophilic and auto-inflammatory dermatoses. Its pathogenesis is unknown, although immune pathways have been implicated. Lesion biopsies show a predominantly neutrophilic infiltrate. The incidence of PG is uncertain, but it is estimated to be 3-10 per million per year, occurring at any age but most commonly between 20 and 50 years with a possible slightly higher incidence in women. Approximately 50% of patients with PG also have another disease associated with PG. The most common is inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis (UC). Local treatment may be sufficient for mild cases, while for severe cases systemic immunosuppressants are the mainstay (1,2). We report the case of a patient with bullous PG and UC successfully treated with infliximab and azathioprine. A 32-year-old male Caucasian patient presented with painful violaceous vesicles and enlarging bullae of various sizes and with acute onset, located on the trunk and bilaterally on both the lower and the upper extremities. Lesions on the trunk were composed of hemorrhagic pustules with a surrounding erythematous overhanging border. Some of the lesions had undergone central necrosis and ulceration (Figure 1, a-d). The patient reported of the lesions had appeared one week ago, simultaneously with the exacerbation of a known inflammatory bowel disease with hemorrhagic mucoid diarrhea and fever of up to 38.5°C. The patient's medical history included UC affecting the whole colon (pancolitis), diagnosed 5 months prior to the onset of the epidermal lesions, for which the patient was receiving treatment with oral prednisolone 10 mg/day and mesalazine granules. Blood tests showed severe anemia, leukocytosis, and increased inflammatory markers (C-reactive protein, erythrocyte sedimentation rate). Antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) andtibodies, antineutrophil

  12. Pyoderma Gangrenosum with Ulcerative Colitis Successfully Treated by the Combination of Granulocyte and Monocyte Adsorption Apheresis and Corticosteroids.

    PubMed

    Ohno, Masashi; Koyama, Shigeki; Ohara, Mariko; Shimamoto, Kazumi; Kobayashi, Yu; Nakamura, Fumiyasu; Mitsuru, Kazuki; Andoh, Akira

    2016-01-01

    A 36-year-old woman was admitted to our hospital due to swelling and redness of the left lateral malleolus and dorsum of the left foot with severe pain, with a flare-up of ulcerative colitis (UC). A pathologic examination by skin biopsy led to a diagnosis of pyoderma gangrenosum (PG). She was treated with the intravenous administration of prednisolone (60 mg/day), and granulocyte and monocyte adsorption apheresis (GMA) was performed twice-a-week for 5 weeks. This treatment dramatically improved both the skin and colonic mucosal lesions. These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC. PMID:26726081

  13. Pyoderma gangrenosum complicated with myelodysplastic syndrome followed by rapidly progressing pyothorax-associated lymphoma: a case report.

    PubMed

    Goto, Akiko; Yamamoto, Satoshi; Notoya, Atsushi; Takada, Akio; Mukai, Masaya

    2006-07-01

    This report describes a patient with pyoderma gangrenosum (PG) complicated with myelodysplastic syndrome (MDS) followed by rapidly progressing pyothorax-associated lymphoma (PAL). A 74-year-old man was admitted with cutaneous gangrene associated with MDS. We diagnosed him as having PG, and high-dose oral prednisolone was started. Two months after admission he developed lymphoma rapidly. The patient died in spite of radiation therapy. On autopsy, the pathological diagnosis was diffuse large cell lymphoma. Epstein-Barr virus (EBV)-encoded RNA, and EBV-encoded nuclear antigen (EBNA) were detected in lymphoma cells. This case suggested that immunosuppressive therapy might favour the clonal proliferation of EBV-infected cells. PMID:16892654

  14. Multimodal Therapy of Ulcers on the Dorsum of the Hand With Exposed Tendons Caused by Pyoderma Gangrenosum.

    PubMed

    Leitsch, Sebastian; Koban, Konstantin Christoph; Pototschnig, Adrian; Titze, Virginia; Giunta, Riccardo Enzo

    2016-03-01

    The authors present the case of a 54-year-old man with ul- cers on the dorsal hand and forearm with exposed extensor tendons after he received misdiagnoses at 2 other hospitals, leading to deep soft tissue defects from multiple debridements. Due to the compli- cated nature of the wound, the ulcers did not heal under the sys- temic medication. After careful debridement, the defect was primar- ily closed with a collagen-glycosaminoglycan biodegradable matrix (Integra Matrix Wound Dressing, Integra LifeSciences, Plainsboro, NJ) on the dorsal hand and covered with a mesh graft 14 days later. Necrosis and superinfection over the index finger was treated again with systemic antibiotics and an unmeshed skin graft under a vacuum bandage with a mesh wound contact layer (Mepitel, Mölnlycke Health Care, Norcross, GA). The patient was satisfied with the functional and aesthetic outcome 1 month later when wounds were completely healed. The authors conclude that in cases where patients are living with pyoderma gangrenosum, even a challenging and complicated wound can be handled successfully with correct systemic immuno- suppression and appropriate soft tissue coverage. PMID:26992198

  15. Dehydrated Human Amnion/Chorion Membrane as Adjunctive Therapy in the Multidisciplinary Treatment of Pyoderma Gangrenosum: A Case Report.

    PubMed

    Snyder, Robert J; Ead, Joey; Glick, Brad; Cuffy, Cherlson

    2015-09-01

    Pyoderma gangrenosum (PG) is an uncommon chronic and progressive skin disorder that can lead to severe tissue necrosis, pathergy, horrendous pain, and disfigurement if not properly and promptly diagnosed and treated. Systemic treatment traditionally consists of long-term immunosuppression. Topical care of the painful wound often represents a clinical challenge. A 77-year-old woman with multiple comorbidities including venous insufficiency and diabetes mellitus was diagnosed through exclusion with refractory, painful PG. She was managed for 3 months by a multidisciplinary team comprised of an internist, 2 dermatologists, and a podiatric wound care specialist using immunosuppressive therapy, several local wound care modalities, and supportive bandages. During that time, severe wound pain continued unabated and the affected area changed from 3 separate wounds measuring 1.4 cm x 1.0 cm x .01 cm, 1.2 cm x 0.5 cm x 0.1 cm, and 0.6 cm x 0.5 cm x 0.1 cm to 1 wound measuring 8.0 cm x 10.3 cm x 0.1 cm. At that time, dehydrated human amnion/chorion membrane (dHACM) allograft, previously reported to facilitate healing venous leg and diabetic foot ulcers, was incorporated into the treatment plan. The patient reported wound pain decreased from 10 out of 10 to 5 out of 10 within hours following application. At the 4 day follow-up visit, she reported no pain; after 1 week, the wound decreased 6.4 cm x 9.4 cm x 0.1 cm in size and after 2 months (3 applications) the wound had reduced in area from 103 cm2 to 57.96 cm2 (reduced by more than half [56%]). In this patient, following the application of dHACM as an adjunct to immunosuppressive therapy, pain receded and wound healing commenced. Additional controlled studies are needed to ascertain the generalizability of this observation. PMID:26367481

  16. 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

  17. 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

  18. 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. PMID:25501066

  19. 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

    2016-01-01

    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. PMID:27530224

  20. 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

  1. 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

  2. Case of pyoderma gangrenosum showing oral and genital ulcers, misdiagnosed as Behcet's disease at first medical examination.

    PubMed

    Tsuboi, Hiromi

    2008-05-01

    It is occasionally difficult to distinguish between Behcet's disease (BD) and pyoderma gangrenous (PG). Our case showed ulcers of the oral, vaginal and perineal areas, and in the ileum, thus resulting in our initial diagnosis of BD. However, the patient showed a continued leukopenia, and she was subsequently diagnosed by bone marrow biopsy as having a myelodysplastic syndrome, which will sometimes accompany PG. In addition, following a hysterectomy, the ulcers of the stump in the vagina and the perineum showed the characteristic findings of a PG-like destructive ulceration. Based on these findings, we finally diagnosed our case to have PG. PMID:18477229

  3. 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

  4. 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

  5. [Presentation of pyoderma gangraenosum in a dermatologic atlas of the early 19th century].

    PubMed

    Kuner, N; Hartschuh, W

    2000-07-01

    Pyoderma gangrenosum was first described in 1930 by Brunsting, Goeckermann and O'Leary. Nevertheless we found some illustrations in an atlas on dermatology, published by Marie-Nicolas Devergie in the first half of the 19th century, which appear to be pyoderma gangrenosum. In addition to discussions of typical syphilitic affections of the skin, Devergie's "Clinique de la Maladie Syphilitique" includes illustrations of gangrenous ulcers, which appeared unexpectedly after local and systemic therapy with mercury. Devergie interpreted those enlarging ulcers as a side effect of mercury therapy. Thus we were able to find evidence of pyoderma gangrenosum more than 100 years before first description in 1930. The etiology of this clinical picture is still unsettled. The favorite postulate has been a bacterial genesis which was the subject of numerous publications until the 1960s. PMID:10969411

  6. [Pyoderma gangraenosum. Case report and comparison with necrotizing fasciitis].

    PubMed

    Heermann, R; Kiehl, P; Issing, P R; Lenarz, T

    2002-03-01

    The differential diagnosis of patients with ulcerative trachelophyma repeatedly causes difficulties. Particularly in view of the possibly fatal outcome, early differentiation between two clinical pictures is very important. Necrotizing fasciitis is often misdiagnosed or the diagnosis is delayed with a mortality rate of approximately 25-40%. It is characterized by local disintegration of the subcutaneous fascia and extensive gangrene of the skin. Sometimes it is not even possible to control the disease using combined antibiotics. Early surgical exploration is mandatory to stop progression of the disease. Pyoderma gangrenosum develops following an initial lesion with pustules and bullae in an ulceration with slight bleeding. Therapy consists of i.v. glucocorticoids (60-200 mg prednisolone/day) administered as early as possible. In complete contrast to the therapy for necrotizing fasciitis, surgical intervention should be strictly avoided in cases of pyoderma gangrenosum. PMID:11975081

  7. Bilateral periorbital ecthyma gangrenosum.

    PubMed

    Ghosheh, Faris R; Kathuria, Sajeev S

    2006-01-01

    We describe a case of bilateral periorbital ecthyma gangrenosum in a diabetic patient with renal failure. Ecthyma gangrenosum is a cutaneous manifestation of Pseudomonas sepsis. We briefly review the pathogenesis of ecthyma gangrenosum and discuss previous reports of periocular involvement. In our patient, conservative measures and supportive care of the periorbital tissue resulted in a good outcome. PMID:17117116

  8. [Gangrenous pyoderma and enterocutaneous fistulas after ileal pouch-anal anastomosis].

    PubMed

    Fadrique, Alfonso García; Ferrer, Francisco Villalba; Esteban, Marcos Bruna; Vila, José Vicente Roig

    2007-05-01

    We describe the medical-surgical management of a patient with a complex inflammatory bowel disease who developed 2 acute episodes of pyoderma gangrenosum and enterocutaneous fistulas after ileal pouch-anal anastomosis for ulcerative colitis. The rarity of this postsurgical complication is emphasized. A good response to topical tacrolimus was achieved in cutaneous wounds. A less favorable response to infliximab was achieved in the abdominal fistulas, requiring surgical excision of the pouch. PMID:17498458

  9. Ecthyma gangrenosum: an important feature of pseudomonal sepsis in a previously well child.

    PubMed

    Goolamali, S I; Fogo, A; Killian, L; Shaikh, H; Brathwaite, N; Ford-Adams, M; Macfarlane, S

    2009-07-01

    Ecthyma gangrenosum is a rare, distinctive skin disorder associated with potentially fatal underlying pseudomonal sepsis. Although typically occurring in neutropenic or immunocompromised patients, it can occasionally affect healthy children. The appearances are characteristic with small indurated vesicular papules progressing rapidly to infarcted necrotic areas with surrounding erythema and a typical black eschar. In young children, these are often accompanied by fever and diarrhoea. The absence of suppuration and slough distinguishes it from the more recognized pyoderma gangrenosum. Lesions can occur at any site although are most commonly found over the buttocks, limbs, axillae and perineum. We describe the case of a 28-month-old, previously well child who presented with typical features of ecthyma gangrenosum secondary to Pseudomonas infection who responded to appropriate antibiotic treatment. Despite a thorough search, no underlying cause was found. Early recognition and prompt treatment with antipseudomonal antibiotics is vital to reduce morbidity and potential mortality. PMID:19094136

  10. 15 CFR 922.47 - Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights. 922.47 Section 922.47 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC...

  11. 15 CFR 922.47 - Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights. 922.47 Section 922.47 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE...

  12. Pre-existing Antibody: Biotherapeutic Modality-Based Review.

    PubMed

    Gorovits, Boris; Clements-Egan, Adrienne; Birchler, Mary; Liang, Meina; Myler, Heather; Peng, Kun; Purushothama, Shobha; Rajadhyaksha, Manoj; Salazar-Fontana, Laura; Sung, Crystal; Xue, Li

    2016-03-01

    Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed. PMID:26821802

  13. Gate dielectric degradation: Pre-existing vs. generated defects

    SciTech Connect

    Veksler, Dmitry E-mail: gennadi.bersuker@sematech.org; Bersuker, Gennadi E-mail: gennadi.bersuker@sematech.org

    2014-01-21

    We consider the possibility that degradation of the electrical characteristics of high-k gate stacks under low voltage stresses of practical interest is caused primarily by activation of pre-existing defects rather than generation of new ones. In nFETs in inversion, in particular, defect activation is suggested to be associated with the capture of an injected electron: in this charged state, defects can participate in a fast exchange of charge carriers with the carrier reservoir (substrate or gate electrode) that constitutes the physical process underlying a variety of electrical measurements. The degradation caused by the activation of pre-existing defects, as opposed to that of new defect generation, is both reversible and exhibits a tendency to saturate through the duration of stress. By using the multi-phonon assisted charge transport description, it is demonstrated that the trap activation concept allows reproducing a variety of experimental results including stress time dependency of the threshold voltage, leakage current, charge pumping current, and low frequency noise. Continuous, long-term degradation described by the power law time dependency is shown to be determined by the activation of defects located in the interfacial SiO{sub 2} layer of the high-k gate stacks. The findings of this study can direct process optimization efforts towards reduction of as-grown precursors of the charge trapping defects as the major factor affecting reliability.

  14. PRESENCE OF PRE-EXISTING ANTIBODIES MEDIATE SURVIVAL IN SEPSIS

    PubMed Central

    Moitra, Rituparna; Beal, Dominic R.; Belikoff, Bryan G.; Remick, Daniel G.

    2011-01-01

    Sepsis is one of the leading causes of death in hospitals worldwide. Even with optimal therapy, severe sepsis results in 50% mortality, indicating variability in the response of individuals towards treatment. We hypothesize that the presence of pre-existing antibodies present in the blood before the onset of sepsis induced by cecal ligation and puncture (CLP) in mice, accounts for the differences in their survival. A Plasma Enhanced Killing (PEK) assay was performed to calculate the PEK capacity of plasma i.e. the ability of plasma to augment PMN killing of bacteria. PEK was calculated as PEK= (1/log (N)) × 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing. A range of PEK in plasma collected from mice prior to CLP was observed, documenting individual differences in bacterial killing capacity. Mortality was predicted based on plasma IL-6 levels at 24 hr post CLP. Mice predicted to die (Die-P) had a lower PEK (<14) and higher peritoneal bacterial counts 24 hr post sepsis compared to those predicted to live (Live-P) with a PEK>16. Mice with PEK<14 were 3.1 times more likely to die compared to the PEK>16 group. To understand the mechanism of defense conferred by the pre-existing antibodies, binding of IgM or IgG to enteric bacteria was documented by flow cytometry. To determine the relative contribution of IgM or IgG, the immunoglobulins were specifically immuno-depleted from the naïve plasma samples and the PEK of the depleted plasma measured. Compared to naïve plasma, depletion of IgM had no effect on the PEK. However, depletion of IgG increased PEK suggesting that an inhibitory IgG binds to antigenic sites on bacteria preventing optimal opsonization of the bacteria. These data demonstrate that prior to CLP; circulating inhibitory IgG antibodies exist that prevent bacterial killing by PMNs in a CLP model of sepsis. PMID:21921828

  15. Ionospheric Current Closure of the Pre-existing Auroral Arc

    NASA Astrophysics Data System (ADS)

    Jiang, F.; Kivelson, M.; Strangeway, R. J.; Khurana, K. K.; Walker, R. J.; Weygand, J. M.

    2014-12-01

    An auroral substorm commences when a discrete auroral arc brightens and subsequently expands poleward and azimuthally. The arc that brightens is usually the most equatorward of several auroral arcs that remain quiescent for ~5 to ~60 minutes before the break-up commences. This arc is often referred to as the "pre-existing auroral arc (PAA)" or the "growth-phase arc". Till now, the ionospheric electrodynamics of the PAA has been studied extensively by ground radar, rockets and low-altitude spacecraft, and it is well established that the field-aligned currents (FAC) associated with the PAA in the ionosphere are current sheets that are narrow in latitude and elongated in longitude. However, it remains a question whether the ionospheric currents that connect the FAC pair of the PAA are meridional or azimuthal. In this study, we have identified ~180 PAA events from FAST measurements in 1998 and 1999 and used the statistics to investigate the ionospheric current closure of the PAA. We calculate the height-integrated Pedersen currents from the electric fields measured by FAST using an empirical ionospheric conductance model and infer the FAC density from the divergence of the Pedersen currents. We find that in the vicinity of the PAA, the FAC density inferred from the divergence of perpendicular currents mimics the trend of the FAC density inferred from magnetic perturbations seen on FAST, and that the boundaries between the upward and the downward FAC sheets inferred from two different approaches lie very close together. Additionally, the latitudinal gradient of the azimuthal component of the magnetic perturbation is much larger than the azimuthal gradient of the meridional component of the magnetic perturbation in the vicinity of the PAA, indicating that the density of a meridional current is much larger than that of an azimuthal current. Our observational analysis strongly suggests that the perpendicular current that closes the FAC pair of the PAA is a north

  16. 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. PMID:23182321

  17. [Ecthyma gangrenosum caused by Staphylococcus aureus].

    PubMed

    Jaque, Alejandra; Moll-Manzur, Catherina; Dossi, María Teresa; Berroeta-Mauriziano, Daniela; Araos-Baeriswyl, Esteban; Monsalve, Ximena

    2016-06-01

    Ecthyma gangrenosum is an uncommon necrotizing vasculitis, in most cases secondary to sepsis by Pseudo-mona aeruginosa in immunocompromised patients. However, there have been several reports of ecthyma gangre-nosum caused by other infectious etiologies. We report an unusual case of ecthyma gangrenosum associated with methicillin-resistant Staphylococcus aureus infection in a patient without the classic immunological risk factors described in the literature. PMID:27598286

  18. 45 CFR 96.111 - Continuation of pre-existing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Continuation of pre-existing regulations. 96.111 Section 96.111 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Transition Provisions § 96.111 Continuation of pre-existing regulations. The regulations previously issued...

  19. Ecthyma gangrenosum in a patient with hypogammaglobulinemia.

    PubMed

    Ng, W; Tan, C L; Yeow, V; Yeo, M; Teo, S H

    1998-05-01

    Ecthyma gangrenosum is a characteristic skin lesion that is caused by Pseudomonas aeruginosa (P. aeruginosa) in the majority of cases. Systemic P. aeruginosa usually complicates debilitating conditions like leukaemia, burns and cystic fibrosis. We report a patient with underlying hypogammaglobulinemia who developed ecthyma gangrenosum secondary to P. aeruginosa septicaemia, which was potentially life-threatening. Recognition of the characteristic skin lesions with prompt initiation of appropriate antibiotics and intravenous immunoglobulins were life-saving. A review of the English literature reports three other cases of ecthyma gangrenosum in patients with underlying hypogammaglobulinemia. PMID:9661949

  20. Ecthyma gangrenosum-like eruption associated with Morganella morganii infection.

    PubMed

    Del Pozo, J; García-Silva, J; Almagro, M; Martínez, W; Nicolas, R; Fonseca, E

    1998-09-01

    Ecthyma gangrenosum is considered as a pathognomonic sign of Pseudomonas aeruginosa sepsis. Lesions similar to ecthyma gangrenosum may be caused by other organisms. We report a case of an ecthyma gangrenosum-like eruption caused by Morganella morganii, a Gram-negative bacillus. PMID:9767304

  1. 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

  2. Ecthyma gangrenosum in Saudi Arabia.

    PubMed

    Obasi, Obasi E; Osoba, Abimbola O; Raddadi, Ali A

    2007-11-01

    We report a diagnosis of ecthyma gangrenosum EG in 4 females of mean age 54.8 range 43-64 years, within 10 months. Severe drug reaction treated with high dose systemic corticosteroids in patient one, acute myelocytic leukemia treated with high dose dexamethasone, and multiple broad-spectrum antibiotics in patient 2 preceded the onset of EG. Patients 3 and 4 had vasculitic purpura and hemodialysis. In addition, patient 3 was receiving multiple broad-spectrum antibiotics plus anti-tuberculosis TB drugs for gastric TB, while patient 4 was on melphalan and high dose systemic corticosteroids. Pseudomonas aeruginosa was isolated from blood culture of the first 3 patients, and skin culture of patient one. Blister aspirate from patient 4 yielded Candida albicans. Factors enhancing skin invasion by pathogenic organisms in our patients were breached skin integrity, therapy with high dose corticosteroids and multiple broad-spectrum antibiotics, hematologic malignancies and chemotherapy with severe neutropenia. PMID:17965803

  3. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status.

    PubMed

    Melnik, Bodo C; Schmitz, Gerd; John, Swen; Carrera-Bastos, Pedro; Lindeberg, Staffan; Cordain, Loren

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual's pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  4. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

    PubMed Central

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual’s pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  5. 13 CFR 120.922 - Pre-existing debt on the Project Property.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pre-existing debt on the Project Property. 120.922 Section 120.922 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS... Project Property. In addition to its share of Project cost, a Third-Party Loan may include...

  6. 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…

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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…

  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. 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. PMID:18375181

  15. Influence of pre-existing salt structures in the 3D pattern of multilayer folding

    NASA Astrophysics Data System (ADS)

    Fernandez, Naiara; Kaus, Boris J. P.; Collignon, Marine

    2014-05-01

    Upward movement of the Precambrian Hormuz salt in the Fars region of the Zagros is supposed to have started as early as Late Cretaceous. The Late Cretaceous - Tertiary deformation events that lead to the folding of the sedimentary cover in this area would have therefore, enhance the upward salt movement by squeezing the pre-existing salt structures. How these salt diapirs evolve under such compressive events has already been previously addressed using analogue models (e.g. Callot et al. 2012). The same authors observed that pre-existing salt structures control the size and geometry of folds in sandbox models. Our previous work has shown that 3D folding instability gives rise to a wide variety of fold shapes (e.g. from dome shape structures to long en echelon or straight anticlines), resulting of the interactions between growing fold segments. The three dimensional growth of these folds, the wavelength and the lateral propagation, is itself controlled by physical parameters. However, the existence of initial weak zones such as pre-existing salt plugs within the sedimentary cover can affect the development of such folds by localizing part of the deformation. In this study we have used numerical modeling to investigate how the fold pattern in 3D multilayer folding is affected by pre-existing salt structures. High-resolution 3D folding simulations (with and without pre-existing salt structures) were performed with the parallel code LaMEM. Cylindrically shaped diapirs with different diameters and heights have been added to a multilayer folding setup. The use of a finite element based landscape evolution model (both erosion and sedimentation) allows for initially buried salt diapirs to be exposed at the surface during folding evolution. Acknowledgements Funding was provided by the European Research Council under the European Community's Seventh Framework program (FP7/2007-2013) ERC Grant agreement #258830. 3D simulations are performed in the IBM Blue Gene/Q JUQUEEN

  16. 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

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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. PMID:27019533

  18. 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

  19. 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.

  20. Inheritance of pre-existing weakness in continental breakup: 3D numerical modeling

    NASA Astrophysics Data System (ADS)

    Liao, Jie; Gerya, Taras

    2013-04-01

    The whole process of continental rifting to seafloor spreading is one of the most important plate tectonics on the earth. There are many questions remained related to this process, most of which are poorly understood, such as how continental rifting transformed into seafloor spreading? How the curved oceanic ridge developed from a single straight continental rift? How the pre-existing weakness in either crust or lithospheric mantle individually influences the continental rifting and oceanic spreading? By employing the state-of-the-art three-dimensional thermomechanical-coupled numerical code (using Eulerian-Lagrangian finite-difference method and marker-in-cell technic) (Gerya and Yuen, 2007), which can model long-term plate extension and large strains, we studied the whole process of continental rifting to seafloor spreading based on the following question: How the pre-existing lithospheric weak zone influences the continental breakup? Continental rifts do not occur randomly, but like to follow the pre-existing weakness (such as fault zones, suture zones, failed rifts, and other tectonic boundaries) in the lithosphere, for instance, the western branch of East African Rift formed in the relatively weak mobile belts along the curved western border of Tanzanian craton (Corti et al., 2007; Nyblade and Brazier, 2002), the Main Ethiopian Rift developed within the Proterozoic mobile belt which is believed to represent a continental collision zone (Keranen and Klemperer, 2008),the Baikal rift formed along the suture between Siberian craton and Sayan-Baikal folded belt (Chemenda et al., 2002). The early stage formed rift can be a template for the future rift development and continental breakup (Keranen and Klemperer, 2008). Lithospheric weakness can either reduce the crustal strength or mantle strength, and leads to the crustal or mantle necking (Dunbar and Sawyer, 1988), which plays an important role on controlling the continental breakup patterns, such as controlling the

  1. Pre-Existing Rotator Cuff Tears as a Predictor of Outcomes in National Football League Athletes

    PubMed Central

    Gibbs, Daniel; Lynch, Thomas Sean; Gomberawalla, M. Mustafa; Schroeder, Greg; LaBelle, Mark; Hollett, Brian P.; Saltzman, Matthew; Nuber, Gordon W.

    2015-01-01

    Objectives: Fifty percent of all athletes at the National Football League (NFL) Combine report having had a shoulder injury at some point during their playing career. Rotator cuff tears are rare injuries in young athletes, but an increasing incidence has been noted amongst competitive football players. It is unknown how pre-existing rotator cuff tears affect career longevity and performance of NFL athletes. In Combine athletes with pre-existing rotator cuff tears, knowledge of outcomes may help athletes and physicians manage expectations of draft potential, career length and performance. Methods: The written medical evaluations of prospective professional American football athletes from 2003-2011 during the NFL Combine were compiled and evaluated. All players were evaluated for the diagnosis of a pre-existing rotator cuff tear and stratified based on whether or not they underwent surgical intervention. Athletes with rotator cuff tears, who were selected in the NFL draft, were matched by age, position, year, and round drafted to control draftees without significant documented shoulder pathology. Career statistics, including a previously established “Performance Score,” were compiled. The continuous variables of each cohort were compared using a Student's t-test. A Chi Squared test was performed to analyze the categorical data. Statistical significance was accepted with a p-value < 0.05. Results: Between the years of 2003 and 2011, 2,965 consecutive athletes were evaluated. Forty-nine athletes were identified with a pre-existing rotator cuff tear; twenty-two of these athletes underwent surgical intervention for their tear and 27 were treated non-operatively. Those who attended the NFL Combine with a history of a rotator cuff tear were significantly less likely to be drafted than those without a previous injury (55.1% vs. 77.5% respectively, p = 0.002) (Table 1A). The 27 drafted athletes with pre-existing rotator cuff tears played significantly fewer years (4.3 vs

  2. Strain Accommodation and its Relationship to Pre-existing Structures along the Karonga Fault, Malawi

    NASA Astrophysics Data System (ADS)

    Dawson, S.; Laó-Dávila, D. A.; Atekwana, E. A.; Clappe, B.; Johnson, T.; Hull, C. D.; Nyalugwe, V.; Abdelsalam, M. G.; Chindandali, P. R. N.; Salima, J.

    2015-12-01

    The Livingstone border fault, with its 7 km of total displacement, accommodates most of the strain in the northern portion of the Malawi Rift. Its hanging wall is also breaking up, as suggested by the 2009 earthquake sequence in Karonga. This hanging wall block is underlain in part by the NW- and N-striking Mughese Shear Zone. The superposition of new faults on the pre-existing structures makes this area an ideal location to study the effect of the orientation of pre-existing structures on the accommodation of strain in the hanging wall in the western flank of the northern Malawi Rift. We used gravity and aeromagnetic data and remote sensing to map the Precambrian macro-scale structural fabric of the greater Karonga region. Moreover, we mapped mesostructures within the Precambrian and younger rocks. In the northern portion of the Karonga fault, a single east-dipping fault zone with a mean strike of 32° and a 59° dip cuts the Precambrian foliation that has a mean strike of 301° and 79° dip, accommodating the majority of strain in this region. South of the city of Karonga, the Precambrian foliation assumes a NNW average strike that is steeply dipping. Here the Karonga fault disperses from a single fault with a 2 km damage zone to several distinct east- and west-dipping faults over 6 km that strike in the same overall direction as the foliation planes from the Mughese Shear Zone. Karoo rift structures (horsts and grabens) and their associated rock formations could also be reactivated in this area. These relationships suggest that within the Malawi Rift, strain can be accommodated differently based on the nature and orientation of pre-existing structures. The structural fabric surrounding the southern portion of the Karonga fault seems to favor reactivation and strain distribution, whereas strain is localized in the northern portion of the fault zone.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the...

  8. 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

    ... Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of... to Part 434—Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining... Maximum Daily Limit at subpart C of this part. In the event that a pollutant concentration in the...

  9. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the...

  10. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the...

  11. 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...

  12. Surrogate-based optimization of hydraulic fracturing in pre-existing fracture networks

    NASA Astrophysics Data System (ADS)

    Chen, Mingjie; Sun, Yunwei; Fu, Pengcheng; Carrigan, Charles R.; Lu, Zhiming; Tong, Charles H.; Buscheck, Thomas A.

    2013-08-01

    Hydraulic fracturing has been used widely to stimulate production of oil, natural gas, and geothermal energy in formations with low natural permeability. Numerical optimization of fracture stimulation often requires a large number of evaluations of objective functions and constraints from forward hydraulic fracturing models, which are computationally expensive and even prohibitive in some situations. Moreover, there are a variety of uncertainties associated with the pre-existing fracture distributions and rock mechanical properties, which affect the optimized decisions for hydraulic fracturing. In this study, a surrogate-based approach is developed for efficient optimization of hydraulic fracturing well design in the presence of natural-system uncertainties. The fractal dimension is derived from the simulated fracturing network as the objective for maximizing energy recovery sweep efficiency. The surrogate model, which is constructed using training data from high-fidelity fracturing models for mapping the relationship between uncertain input parameters and the fractal dimension, provides fast approximation of the objective functions and constraints. A suite of surrogate models constructed using different fitting methods is evaluated and validated for fast predictions. Global sensitivity analysis is conducted to gain insights into the impact of the input variables on the output of interest, and further used for parameter screening. The high efficiency of the surrogate-based approach is demonstrated for three optimization scenarios with different and uncertain ambient conditions. Our results suggest the critical importance of considering uncertain pre-existing fracture networks in optimization studies of hydraulic fracturing.

  13. Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery.

    PubMed

    Rojas, Luis Alfonso; Condezo, Gabriela N; Moreno, Rafael; Fajardo, Carlos Alberto; Arias-Badia, Marcel; San Martín, Carmen; Alemany, Ramon

    2016-09-10

    Recombinant adenoviruses are used as vaccines, gene therapy vectors, and oncolytic viruses. However, the efficacy of such therapies is limited by pre-existing neutralizing antibodies (NAbs), especially when the virus is administered systemically for a wider biodistribution or to reach multiple metastases. To protect adenovirus against NAbs we inserted an albumin-binding domain (ABD) in the main adenovirus capsid protein, the hexon. This domain binds serum albumin to shield the virus upon systemic administration. The ABD-modified adenoviruses bind human and mouse albumin and maintain the infectivity and replication capacity in presence of NAbs. In pre-immunized mice non-modified viruses are completely neutralized, whereas ABD-modified viruses preserve the ability to transduce target organs, induce oncolysis, or generate immune responses to expressed proteins. Our results indicate that albumin coating of the virus capsid represents an effective approach to evade pre-existing NAbs. This strategy has translational relevance in the use of adenovirus for gene therapy, cancer virotherapy, and vaccination. PMID:27388756

  14. Bortezomib reduces pre-existing antibodies to recombinant immunotoxins in mice.

    PubMed

    Manning, Michael L; Mason-Osann, Emily; Onda, Masanori; Pastan, Ira

    2015-02-15

    Recombinant immunotoxin (RIT) therapy is limited in patients by neutralizing Ab responses. Ninety percent of patients with normal immune systems make neutralizing Abs after one cycle of RIT, preventing repeated dosing. Furthermore, some patients have pre-existing Abs from environmental exposure to Pseudomonas exotoxin, the component of the RIT that elicits the neutralizing Ab response. Bortezomib is an U.S. Food and Drug Administration-approved proteasome inhibitor that selectively targets and kills plasma cells that are necessary for the neutralizing Ab response. We hypothesized that bortezomib may abrogate neutralizing Ab levels, making dosing of RIT possible in mice already immune to RIT. We immunized BALB/c mice with multiple doses of SS1P, a RIT whose Ab portion targets mesothelin. Mice with elevated Ab levels were separated into groups to receive saline, bortezomib, the pentostatin/cyclophosphamide (PC) regimen, or the bortezomib/PC (BPC) combination regimen. Four weeks after finishing therapy, plasma Ab levels were assayed, and bone marrow was harvested. The bortezomib and PC regimens significantly reduced Ab levels, and we observed fewer plasma cells in the bone marrow of bortezomib-treated mice but not in PC-treated mice. The BPC combination regimen almost completely eliminated Abs and further reduced plasma cells in the bone marrow. This regimen is more effective than individual regimens and may reduce Ab levels in patients with pre-existing neutralizing Abs to Pseudomonas exotoxin, allowing RIT treatment. PMID:25560410

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

    PubMed

    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

  16. 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.

  17. 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

  18. 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. PMID:23160797

  19. A case of perineal ecthyma gangrenosum.

    PubMed

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

    2016-03-01

    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

  20. 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

  1. 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.

  2. 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).

  3. Gene Therapy for Mucopolysaccharidosis Type VI Is Effective in Cats Without Pre-Existing Immunity to AAV8

    PubMed Central

    Ferla, Rita; O'Malley, Thomas; Calcedo, Roberto; O'Donnell, Patricia; Wang, Ping; Cotugno, Gabriella; Claudiani, Pamela; Wilson, James M.; Haskins, Mark

    2013-01-01

    Abstract Liver gene transfer with adeno-associated viral (AAV) 2/8 vectors is being considered for therapy of systemic diseases like mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease due to deficiency of arylsulfatase B (ARSB). We have previously reported that liver gene transfer with AAV2/8 results in sustained yet variable expression of ARSB. We hypothesized that the variability we observed could be due to pre-existing immunity to wild-type AAV8. To test this, we compared the levels of AAV2/8-mediated transduction in MPS VI cats with and without pre-existing immunity to AAV8. In addition, since levels of lysosomal enzymes as low as 5% of normal are expected to be therapeutic, we evaluated the impact of pre-existing immunity on MPS VI phenotypic rescue. AAV2/8 administration to MPS VI cats without pre-existing neutralizing antibodies to AAV8 resulted in consistent and dose-dependent expression of ARSB, urinary glycosaminoglycan (GAG) reduction, and femur length amelioration. Conversely, animals with pre-existing immunity to AAV8 showed low levels of ARSB expression and limited phenotypic improvement. Our data support the use of AAV2/8-mediated gene transfer for MPS VI and other systemic diseases, and highlight that pre-existing immunity to AAV8 should be considered in determining subject eligibility for therapy. PMID:23194248

  4. Mechanical and microstructural development of Carrara marble with pre-existing deformation history in torsion experiments

    NASA Astrophysics Data System (ADS)

    Bruijn, R. H. C.; Burlini, L.; Kunze, K.

    2009-04-01

    The deformation behaviour of Carrara marble has been studied mostly by performing deformation experiments on initially undeformed samples. In this study, torsion experiments on Carrara marble with a pre-existing deformation history have been conducted and analysed in terms of both mechanical and microstructural development. Torsion experiments have been conducted to deform initially deformed Carrara marble samples until a bulk shear strain of gamma 1 or 2.6 was reached. For Carrara marble experiments typically yielding is followed by strain hardening until a peak stress is reached around a shear strain gamma = 1 , after which a weakening phase occurs. Weakening gradually develops into a steady-state creep. During hardening, a shear microstructure and CPO develops; afterwards dynamic recrystallization becomes increasingly effective resulting in pervasively recrystallized microstructure and recrystallization CPO at gamma 5 and higher. Starting material of the new experiments are sandwich samples consisting of three equally sized segments: a top segment previously deformed counter clockwise, an undeformed centre segment and a previously clockwise deformed segment in the bottom. Shear strain of the deformed bottom and top segments are equal in magnitude but opposite in sense and correspond with the shear strain of the actual experiments (e.g. sample of the gamma 1 experiment, consists of initially gamma 1 deformed top and bottom segments). All torsion experiments were conducted using a Paterson type internally heated gas-medium deformation apparatus equipped with a torsion actuator, under temperature and pressure conditions of 1000K and 300 MPa, respectively. Angular displacement rates during the experiments correspond to a strain rate of 3.0x10-4 s-1 at the outer cylinder periphery. The second deformation event imposed on the sandwich sample is always counter clockwise (or dextral). The sandwich experiment to gamma 1 shows a weakly developed strain partitioning

  5. 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.

  6. The Influence of Pre-existing Deformation on GMA Welding Distortion in Thin Steel Plates

    NASA Astrophysics Data System (ADS)

    Davies, C. M.; Ahn, J.; Tsunori, M.; Dye, D.; Nikbin, K. M.

    2015-01-01

    Weld distortion is particularly problematic for large thin structures that are used in the assembly of ships. The drive toward lighter ships and thinner plate is restricted by the significant increase in distortion as the plate thickness decreases. The influence of pre-existing deformation in the plates to be joined on the resultant distortion in gas metal arc welded structure has been studied. DH-36 steel plate surface profiles were measured before and after the butt welding of two plates 1000 × 500 × 4 mm in size. Three dimensional finite element models that incorporate the initial plate profile have been created to simulate the welding process and to examine the relationship between the final welded plate profiles and the initial deformation present in the plates. Both symmetric and asymmetric models were considered. A significant variation in the unwelded base plates' initial distortion was observed. Generally, it has been found that if an out-of-plane deformation exists in a plate prior to welding, the level of distortion further increases in the same direction following welding. The final distortions are strongly related to the initial plate profiles. The residual stress distributions in the plates are also to some extent affected by the level of distortion initially present.

  7. 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.

  8. TCR Microclusters pre-exist and contain molecules necessary for TCR signal transduction.

    PubMed

    Crites, Travis J; Padhan, Kartika; Muller, James; Krogsgaard, Michelle; Gudla, Prabhakar R; Lockett, Stephen J; Varma, Rajat

    2014-07-01

    TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These pre-existing microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters linker for activation of T cells and growth factor receptor-bound protein 2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could explain, in part, the rapid kinetics with which TCR signal transduction occurs. PMID:24860189

  9. 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.

  10. 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. PMID:17211226

  11. Pyoderma gangraenosum caused by Rhizopus arrhizus.

    PubMed

    Liao, W Q; Yao, Z R; Li, Z Q; Xu, H; Zhao, J

    1995-01-01

    A rare case of pyoderma gangraenosum caused by Rhizopus arrhizus is reported. The patient, a 50-year-old male farmer, was admitted to hospital complaining of gangrening and festering of the right upper arm with severe pain for nearly 2 months. A lesion was found on the inside of right upper arm. The central skin part of the lesion became black dry gangrenous, the periphery was deeply ulcerated with yellow-green pus. The necrotic crust, biceps, triceps and vessels inherited a histopathologically proven fungal infection. The fungus isolated was identified as Rhizopus arrhizus. The infection was successfully treated with itraconazole. PMID:7637685

  12. 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. PMID:25294050

  13. Morbidity risks among older adults with pre-existing age-related diseases.

    PubMed

    Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Kulminski, Alexander; Yashin, Anatoliy I

    2013-12-01

    Multi-morbidity is common among older adults; however, for many aging-related diseases there is no information for U.S. elderly population on how earlier-manifested disease affects the risk of another disease manifested later during patient's lifetime. Quantitative evaluation of risks of cancer and non-cancer diseases for older adults with pre-existing conditions is performed using the Surveillance, Epidemiology, and End Results (SEER) Registry data linked to the Medicare Files of Service Use (MFSU). Using the SEER-Medicare data containing individual records for 2,154,598 individuals, we empirically evaluated age patterns of incidence of age-associated diseases diagnosed after the onset of earlier manifested disease and compared these patterns with those in general population. Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services/procedures, and Medicare enrollment/disenrollment. More than threefold increase of subsequent diseases risk was observed for 15 disease pairs, majority of them were i) diseases of the same organ and/or system (e.g., Parkinson disease for patients with Alzheimer disease, HR=3.77, kidney cancer for patients with renal failure, HR=3.28) or ii) disease pairs with primary diseases being fast-progressive cancers (i.e., lung, kidney, and pancreas), e.g., ulcer (HR=4.68) and melanoma (HR=4.15) for patients with pancreatic cancer. Lower risk of subsequent disease was registered for 20 disease pairs, mostly among patients with Alzheimer's or Parkinson's disease, e.g., decreased lung cancer risk among patients with Alzheimer's (HR=0.64) and Parkinson's (HR=0.60) disease. Synergistic and antagonistic dependences in geriatric disease risks were observed among US elderly confirming known and detecting new associations of wide spectrum of age-associated diseases. The results can be used in optimization of screening, prevention and treatment strategies of chronic diseases among U.S. elderly

  14. Ecthyma gangrenosum and neutropenia in a previously healthy child.

    PubMed

    Pacha, Omar; Hebert, Adelaide A

    2013-01-01

    Ecthyma gangrenosum is the cutaneous manifestation of pseudomonas infection in patients with sepsis. A previously healthy 7-month-old girl who developed ecthyma gangrenosum without apparent inciting factors became neutropenic secondary to autoimmune neutropenia 2 months after initial presentation. She was treated with appropriate surgical and medical intervention and was discharged in stable condition only to die suddenly 2 days after discharge. PMID:22471737

  15. Detection and Management of Pre-Existing Cognitive Impairment and Associated Behavioral Symptoms in the Intensive Care Unit

    PubMed Central

    Lee, Hochang B.; DeLoatch, Candyce J.; Cho, SeongJin; Rosenberg, Paul; Mears, Simon C.; Sieber, Frederick E.

    2008-01-01

    Recent increase in both the elderly population and associated incidence of dementia are of critical importance to patient care in intensive care units (ICU) in the United States. Identification of pre-existing cognitive impairment such as mild cognitive impairment and dementia could prevent delirium and associated morbidity and mortality in ICU. Additionally, non-cognitive behavioral symptoms such as depression, psychosis, agitation, and catastrophic reactions are common in patients with pre-existing cognitive impairment. Detection and management of non-cognitive behavioral symptoms associated with demented elderly patients in ICU leads to improved delivery of life-saving critical care. PMID:18929940

  16. Detection and management of pre-existing cognitive impairment and associated behavioral symptoms in the Intensive Care Unit.

    PubMed

    Lee, Hochang B; DeLoatch, Candyce J; Cho, SeongJin; Rosenberg, Paul; Mears, Simon C; Sieber, Frederick E

    2008-10-01

    Recent increase in both the elderly population and associated incidence of dementia are of critical importance to patient care in ICUs in the United States. Identification of pre-existing cognitive impairment, such as mild cognitive impairment and dementia, could prevent delirium and associated morbidity and mortality in the ICU. Additionally, noncognitive behavioral symptoms, such as depression, psychosis, agitation, and catastrophic reactions, are common in patients with pre-existing cognitive impairment. Detection and management of noncognitive behavioral symptoms associated with MRI and dementia in ICU leads to improved delivery of life-saving critical care. PMID:18929940

  17. [Whiplash injury of the cervical spine--on the role of pre-existing degenerative diseases].

    PubMed

    Meenen, N M; Katzer, A; Dihlmann, S W; Held, S; Fyfe, I; Jungbluth, K H

    1994-06-01

    Radiological investigations contribute little in differentiating the problems of patients with whiplash injuries. Nevertheless the more prolonged cases of whiplash injuries must not be attributed to preexisting degenerative disease, despite radiologically-proven medicolegal opinion. In this study, 60 patients who were seen for whiplash injuries in the Department for Trauma and Reconstructive Surgery at the University Hospital Hamburg-Eppendorf for clinical and radiological evaluation, an average of 5.7 years post injury, were divided into two groups (n = 30) depending on radiologically-proven preexisting degenerative changes of the cervical spine. On average the patients with degenerative changes were 11.2 years older than those with healthy vertebral columns and also demonstrated an increase in acute symptoms in the lower cervical spine (cervicobrachial syndrome). The chronicity of individual symptoms such as neck-pain, dizziness, nausea and psychological illness was also observed in both groups. Problems such as paresthesias as well as pain in the shoulder-arm-area appeared to increase in subsequent check-ups, irrespective of the earlier degenerative changes. Patients with typical posterior headaches recovered faster when they had radiologically normal spines. Presenting late, there was a significant accumulation of patients with pre-existing degenerative changes complaining merely of tinnitus. The earlier changes in any individual motion segment do not determine the clinical course of whiplash injuries, but merely represent an area of increased vulnerability to trauma. On the other hand, trauma has not been proven to influence the development or aggravation of degenerative changes in normal or diseased spines. We are not able to differentiate the posttraumatic course from the natural history of the degenerative process, either clinically or radiologically. Considering the involvement of sensitive neurological structures the classical objective organic diagnosis

  18. Reactivation of pre-existing structures during Palaeogene to recent tectonics - the Southern Upper Rhine Graben

    NASA Astrophysics Data System (ADS)

    Ustaszewski, K.; Schumacher, M.; Schmid, S. M.

    2003-04-01

    Contour maps of the top-basement surface were established for part of the southernmost Upper Rhine Graben and the adjacent Jura Mountains based on seismic reflection profiles. Combined with surface data, they emphasise the importance of pre-existing Palaeozoic faults for the Palaeogene to recent structural evolution of the southern Upper Rhine Graben, an area of increased seismicity. The contemporaneous opening of the Palaeogene Upper Rhine Graben and Bresse Graben systems was kinematically linked by the Rhine-Bresse transform zone (RBTZ). The RBTZ formed along ENE-oriented crustal discontinuities, inherited from post-Variscan transtension. This Palaeogene rifting initiated in Late Priabonian times and encompassed sinistral transtensive reactivation of ENE-oriented basement faults and normal faulting along NNE-striking faults during ESE-WNW-directed extension. In the Mesozoic sedimentary cover these movements were accommodated by the formation of ENE-oriented flexures and NNE-striking half-grabens with hanging-wall growth faults. Mio- to Pliocene thin-skinned folding and thrusting of the Jura Mountains encountered a rift-related structural pattern, which had disrupted the Triassic basal décollement. This inherited pattern controlled the nucleation of thrusts and folds, as well as transfer zones, in the detached sedimentary cover, as is evidenced in the high semblance of subsurface faults and surface structures. Horizontal transport directions of the detached sediments (reconstructed by fault plane inversion) reveal NW- to NNE-directed fan-shaped trajectories, which indicate divergent displacements at the thin-skinned Jura front. On the other hand, increasing transpressional shortening of the frontal thrust sheet towards W with a maximum in the proximity of NNE-striking basement faults suggests a clockwise rotation of the detached sediments. Post-2.9Ma shortening of the sedimentary cover is evidenced in an array of ENE- to NE-trending syn- and anticlines, deforming

  19. Increased Susceptibility to Chemical Toxicity with (Pre-existing) Diseases: Case Studies with Particulate Matter, Cadmium, Mercury, Trichloroethylene and Dioxin

    EPA Science Inventory

    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 increas...

  20. Diagnosis and Management of Drug-Induced Liver Injury (DILI) in Patients with Pre-Existing Liver Disease.

    PubMed

    Teschke, Rolf; Danan, Gaby

    2016-08-01

    The relationship between drugs and pre-existing liver disease is complex, particularly when increased liver tests (LTs) or new symptoms emerge in patients with pre-existing liver disease during drug therapy. This requires two strategies to assess whether these changes are due to drug-induced liver injury (DILI) as a new event or due to flares of the underlying liver disease. Lacking a valid diagnostic biomarker, DILI is a diagnosis of exclusion and requires causality assessment by RUCAM, the Roussel Uclaf Causality Assessment Method, to establish an individual causality grading of the suspected drug(s). Flares of pre-existing liver disease can reliably be assessed in some hepatotropic virus infections by polymerase chain reaction (PCR) and antibody titers at the beginning and in the clinical course to ascertain flares during the natural course of the disease. Unfortunately, flares cannot be verified in many other liver diseases such as alcoholic liver disease, since specific tests are unavailable. However, such a diagnostic approach using RUCAM applied to suspected DILI cases includes clinical and biological markers of pre-existing liver diseases and would determine whether drugs or underlying liver diseases caused the LT abnormalities or the new symptoms. More importantly, a clear diagnosis is essential to ensure effective disease management by drug cessation or specific treatment of the flare up due to the underlying disease. PMID:27091053

  1. 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

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COAL MINING...

  2. Increased Susceptibility to Chemical Toxicity with Pre-existing Diseases: Case Studies with Particulate Matter, Cadmium, Mercury, Trichloroethylene and Dioxin

    EPA Science Inventory

    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 increase...

  3. 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.

  4. Molecular dynamics study on the interactions between helium projectiles and helium bubbles pre-existing in tungsten surfaces

    NASA Astrophysics Data System (ADS)

    Ding, Yuan; Ma, Chaoqiong; Li, Min; Hou, Qing

    2016-02-01

    Molecular dynamics simulations were performed to study the interactions between low-energy (⩽100 eV) helium (He) projectiles and helium bubbles pre-existing near tungsten (W) surfaces. It is observed that with increasing bubble size, the reflection coefficient of the He projectiles was reduced, and the channelling effect that could be observed with no pre-existing He bubble was depressed. The He projectiles can be captured by pre-existing He bubbles and also knock He atoms out of the bubbles. The spatial distribution of the single He atoms, including both the slowed-down projectiles and the knocked-out He atoms, was extracted. The single He atoms were found distributed around the bubbles in a region with the width of 3-5.5 in lattice lengths of W. Although the results were obtained for the interaction of He projectiles with isolated He bubbles pre-existing in W, they suggest that the reflection and retention status of He projectiles would change during the irradiation of high flux/fluence He on W surfaces due to the change of He bubbles coverage near W surfaces. The results can be coupled with Monte Carlo modelling in conditions closer to that in experiments of high flux/fluence He bombardments on W surfaces.

  5. 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. PMID:26191923

  6. 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. PMID:20558090

  7. Phenotypic T Cell Exhaustion in a Murine Model of Bacterial Infection in the Setting of Pre-Existing Malignancy

    PubMed Central

    Mittal, Rohit; Wagener, Maylene; Breed, Elise R.; Liang, Zhe; Yoseph, Benyam P.; Burd, Eileen M.; Farris, Alton B.

    2014-01-01

    While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation. PMID:24796533

  8. Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.

    PubMed

    Mittal, Rohit; Wagener, Maylene; Breed, Elise R; Liang, Zhe; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M; Ford, Mandy L

    2014-01-01

    While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation. PMID:24796533

  9. An Extraordinary Cause of the Sucking Difficulty: Ecthyma Gangrenosum

    PubMed Central

    Demir, Nihat; Kocaman, Selami; Peker, Erdal; Tuncer, Oğuz

    2016-01-01

    Ecthyma gangrenosum is a cutaneous lesion often associated with pseudomonas aeruginosa bacteremia, even though it may develop without bacteremia and may originate from other bacterial and fungal organisms. Pseudomonas aeruginosa bacteremia or sepsis, which mainly affects immunocompromised patients, frequently occurs in hospitals. This lesion typically occurs on the extremities and gluteal and perineal regions. In this report we present a case of ecthyma gangrenosum in a premature newborn occurring secondary to pseudomonas sepsis causing sucking dysfunction due to tissue loss in the lip, soft palate, and tongue. PMID:27143976

  10. 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. PMID:26423787

  11. Simple scaling laws for the role of pre-existing and shock-induced microstructure on spall strength

    NASA Astrophysics Data System (ADS)

    Wilkerson, Justin; Ramesh, Kt

    2015-06-01

    Failure of ductile metals has long been attributed to void nucleation, growth, and finally coalescence leading to fracture. Under extreme loading conditions, a number of experimental investigations have demonstrated a strong rate-dependence in the dynamic tensile strength of such metals, which may be attributed to the fact that voids are constrained to grow at finite rates. Here we show that bounds on these void growth rates may be derived analytically by considering the constraints imposed by micro-inertia as well as relativistic dislocation drag. We then make use of these bounds to derive simple scaling laws for predicting the rate-dependence of spall strength. Though simple, the derived scaling laws compare well with experimental measurements and prove useful in shedding light on some of the more perplexing observations associated with spall failure. In particular, the scaling laws are helpful in understanding the role of pre-existing microstructure, e.g. second-phase particle spacing and grain size, on the spall strength of metals. Under typical loading conditions, we find that the spall strength is governed by this pre-existing microstructure with void growth governed primarily by micro-inertia. However, under the most extreme loading conditions, we find that the spall strength is governed instead by the shock-induced microstructure with growth mediated by dislocation emission. Lastly, we demonstrate how the scaling laws may be utilized to optimize the pre-existing microstructure, e.g. grain size considering the Hall-Petch effect, of a material for a particular application.

  12. 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. PMID:25848870

  13. Ecthyma gangrenosum in a premature low-birth-weight newborn.

    PubMed

    Basu, S; Kumar, A

    2011-12-01

    Ecthyma gangrenosum is a well-recognised cutaneous infection in critically ill and immunocompromised patients. It is commonly associated with Pseudomonas aeruginosa septicaemia. Classic lesions of ecthyma gangrenosum comprise deep ulcers with ecchymotic, gangrenous centres, bright red areolae and typical raised, purplish, indurated, rolled-out edges. We report ecthyma gangrenosum in a premature low-birth-weight neonate, delivered at home to a third gravida mother with history of chorioamnionitis. He was admitted to a private hospital on third day of life, with a diagnosis of early-onset neonatal sepsis and received multiple antibiotics over next 22 days. The infant was referred to the paediatrics emergency department of Sir Sunderlal Hospital, Banaras Hindu University in a condition of shock, pneumonitis and generalised sepsis. Two gangrenous ulcers with gray-black eschar were present, one over the neck and another over the back. He was diagnosed as a case of neonatal sepsis with ecthyma gangrenosum. Blood culture revealed growth of Pseudomonas aeruginosa, sensitive only to imipenem. The infant died the day following admission. PMID:22240885

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

    PubMed

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

    2013-11-01

    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

  15. Impact of Pre-Existing Immunity on Gene Transfer to Nonhuman Primate Liver with Adeno-Associated Virus 8 Vectors

    PubMed Central

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

    2011-01-01

    Abstract 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. PMID:21476868

  16. 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

  17. 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.

  18. [Pyoderma gangraenosum--a rare complication after breast reduction].

    PubMed

    Gruhl, L; Bruck, J C; Merkel, K; Büttemeyer, R; Grabosch, A

    1992-01-01

    Applying standardized and sound operative techniques, impaired wound healing following reduction mammoplasty is rare. A postoperative case of pyoderma gangraenosum is reported. This necrotizing skin disorder seemed at first to be a postoperative bacterial infection, but correct diagnosis was finally made histopathologically. The clinical course, etiology, diagnostic findings, and therapy are discussed and a review of the literature is presented. PMID:1568675

  19. 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. PMID:26962806

  20. 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

  1. Basaloid Squamous Cell Carcinoma of Scalp From A Pre-Existing Cylindroma Metastasising To Brain: A Rare Case Report

    PubMed Central

    Srinivas, Teerthanath; Kolakebail, Jayaram Shetty; Shetty, Jayaprakash; Kukreja, Prachi

    2016-01-01

    Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and accounts for 90% of head and neck malignancies. Intracranial metastases of SCC are extremely rare. We are reporting a case of 55-year-old female with history of recurrent swelling over right side of forehead which was previously reported as cylindroma. CT scan of head revealed irregular lytic areas in right frontal bone suggestive of erosion. There were multiple small, rim enhancing lesions in bilateral parietal regions. Clinically it was diagnosed as malignant adnexal tumour. Wide excision of the lesion revealed features of invasive basaloid squamous cell carcinoma, probably a malignant transformation of the pre-existing cylindroma. PMID:27437239

  2. A possible role of pre-existing IgM/IgG antibodies in determining immune response type.

    PubMed

    Seledtsov, V I; Seledtsova, G V

    1997-04-01

    On the basis of the data indicating the existence of two types of immuno-protection, namely macrophage-mediated and mast cell-basophil-mediated, it is argued that by reacting with potential pathogens, pre-existing IgM and IgG antibodies (both natural and induced by environmental microflora) might promote involvement of macrophages in the presentation process, favouring the generation of pathogen-specific T helper 1 (Th1), but not Th2, responses. Alternatively, the failure of these antibodies to effectively recognize pathogens might be associated with active involvement of pathogen-specific B cells in presenting Ag and, as a consequence, with the predominant development of Th2, rather than Th1, responses. PMID:9107571

  3. A historical pyroclastic flow emplaced within a pre-existing Pleistocene lava tube: Silidong, Tianchi Volcano, Changbaishan, northeastern China

    NASA Astrophysics Data System (ADS)

    Chen, Zhengquan; Wei, Haiquan; Liu, Yongshun; Tilling, Robert I.; Xu, Jiandong; Wu, Chengzhi; Nie, Baofeng

    2015-06-01

    Pyroclastic flow deposits recently found within a pre-existing lava tube at Tianchi Volcano represent, to the best of our knowledge, the only such reported occurrence worldwide. In this case, pyroclastic flow of Tianchi's "Millennium eruption" (~1 ka) traveled about 18 km from the summit eruptive source and poured successively into the ~560-m-long accessible segment of Silidong lava tube. Mapping of tube morphology, combined with detailed characterization of the features associated with the pumice flow deposits (e.g., adhering of pyroclastic materials on tube walls, fumarole pipes, rootless vents, and flow fronts of the deposit surface) has enabled plausible inferences regarding the original within-tube conditions and dynamic flow regime during emplacement. We propose a model of an aggrading pyroclastic flow which locally varies its sedimentation rate. The pyroclastic deposit is thicker in locations of reduced flow mobility, and the resultant variations in deposit thickness appear to control the distribution of fumarole pipes and rootless vents.

  4. Pre-existing Minority Drug-Resistant HIV-1 Variants, Adherence, and Risk of Antiretroviral Treatment Failure

    PubMed Central

    Paredes, Roger; Lalama, Christina M.; Ribaudo, Heather J.; Schackman, Bruce R.; Shikuma, Cecilia; Giguel, Francoise; Meyer, William A.; Johnson, Victoria A.; Fiscus, Susan A.; D’Aquila, Richard T.; Gulick, Roy M.; Kuritzkes, Daniel R.

    2009-01-01

    Background The clinical relevance of detecting minority drug-resistant HIV-1 variants is uncertain. Methods To determine the effect of pre-existing minority non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant variants on the risk of virologic failure (VF), we reanalyzed a case-cohort substudy of efavirenz recipients in ACTG A5095. Minority K103N or Y181C populations were determined by allele-specific PCR (ASPCR) in subjects without NNRTI resistance by population sequencing. Weighted Cox proportional hazards models adjusted for recent adherence estimated the relative risk of VF in the presence of NNRTI-resistant minority variants. Results The evaluable case-cohort sample included 195 subjects from the randomly selected subcohort (51 with VF, 144 without failure [NF]), plus 127 of the remaining subjects with VF. Presence of minority K103N or Y181C mutations, or both, was detected in 8 (4.4%), 54 (29.5%) and 11 (6%), respectively, of 183 evaluable subjects in the random subcohort. Detection of minority Y181C mutants was associated with an increased risk of VF in the setting of recent adherence (HR=3.45, CI=1.90, 6.26), but not in non-adherent subjects (HR=1.39, CI=0.58, 3.29). Of note, 70% of subjects with minority Y181C achieved long-term viral suppression. Conclusions In adherent patients, pre-existing minority Y181C mutants more than tripled the risk of VF of first-line efavirenz-based ART. PMID:20102271

  5. Numerical modeling of the seismic response of a large pre-existing landslide in the Marmara region

    NASA Astrophysics Data System (ADS)

    Bourdeau, Céline; Lenti, Luca; Martino, Salvatore

    2015-04-01

    Turkey is one of the geologically most active regions of Europe prone to natural hazards in particular earthquakes and landslides. Detailed seismological studies show that a catastrophic event is now expected in the Marmara region along the North Anatolian Fault Zone (NAFZ). On the shores of the Marmara sea, about 30km East of Istanbul and 15km North from the NAFZ, urbanization is fastly growing despite the presence of pre-existing large landslides. Whether such landslides could be reactivated under seismic shaking is a key question. In the framework of the MARsite European project, we selected one of the most critical landslides namely the Büyükçekmece landslide in order to assess its local seismic response. Based on detailed geophysical and geotechnical field investigations, a high-resolution engineering-geological model of the landslide slope was reconstructed. A numerical modeling was carried out on a longitudinal cross section of this landslide with a 2D finite difference code FLAC in order to assess the local seismic response of the slope and to evaluate the consistency of conditions suitable for the earthquake-induced reactivation of the landslide. The obtained ground-motion amplification pattern along the slope surface is very complex and is strongly influenced by properties changes between the pre-existing landslide mass and the surrounding material. Further comparisons of 2D versus 1D ground-motion amplifications on the one hand and 2D versus topographic site effects on the other hand will shed light on the parameters controlling the spatial variations of ground-motion amplifications along the slope surface.

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

    PubMed Central

    Kang, Zhou-Qing; Zhai, Xiao-Jie

    2015-01-01

    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 12053 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, I2 = 51.1%]. Estimates by type of surgery suggested similar results in cardiac surgery [OR = 2.00, 95% CI = 1.42–2.82, I2 = 0%], in general surgery [OR = 1.75, 95% CI = 1.42–2.15, I2 = 0%], and in major lower limb amputations [OR = 1.65, 95% CI = 1.01–2.68, I2 = 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, I2 = 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. PMID:26260124

  7. Primary ecthyma gangrenosum as a presenting sign of leukemia in a child.

    PubMed

    Fink, Matthew; Conrad, Dennis; Matthews, Mark; Browning, John C

    2012-03-01

    Ecthyma gangrenosum is a type of skin infection characterized by black eschars on an erythematous base. It most commonly occurs with pseudomonas infection in an immunocompromised setting. We present a case of primary ecthyma gangrenosum as the presenting sign of pre-B acute lymphoblastic leukemia (ALL) in a child. PMID:22483514

  8. 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

  9. 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

  10. A Model for Subglacial Flooding Along a Pre-Existing Hydrological Network during the Rapid Drainage of Supraglacial Lakes

    NASA Astrophysics Data System (ADS)

    Adhikari, S.; Tsai, V. C.

    2014-12-01

    Increasingly large numbers of supraglacial lakes form and drain every summer on the Greenland Ice Sheet. Presently, about 15% of the lakes drain rapidly within the timescale of a few hours, and the vertical discharge of water during these events may find a pre-existing subglacial hydrological network, particularly late in the melt season. Here, we present a model for subglacial flooding applied specifically to such circumstances. Given the short timescale of events, we treat ice and bed as purely elastic and assume that the fluid flow in the subglacial conduit is fully turbulent. We evaluate the effect of initial conduit opening, wi, on the rate of flood propagation and along-flow profiles of field variables. We find that floods propagate much faster, particularly in early times, for larger wi. For wi = 10 and 1 cm, for example, floods travel about 68% and 50% farther than in the fully coupled ice/bed scenario after 2 hours of drainage, respectively. Irrespective of the magnitude of wi, we also find that there exists a region of positive pressure gradient. This reversal of pressure gradient draws water in from the farfield and causes the conduit to narrow, respecting mass continuity. While the general shape of the profiles appears similar, greater conduit opening is found for larger wi. For wi = 10 and 1 cm, for example, the elastostatic conduit opening at the point of injection is about 1.39 and 1.26 times that of the fully coupled ice/bed scenario after 2 hours of drainage. The hypothesis of a pre-existing thin film of water is consistent with the spirit of contemporary state-of-the-art continuum models for subglacial hydrology. This also results in avoiding the pressure singularity, which is inherent in classical hydro-fracture models applied to fully coupled ice/bed scenarios, thus opening an avenue for integrating the likes of our model within continuum hydrological models. Furthermore, we foresee that the theory presented can be used to potentially infer

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer

    PubMed Central

    Kristian, Sascha A.; Hwang, John H.; Hall, Bradley; Leire, Emma; Iacomini, John; Old, Robert; Galili, Uri; Roberts, Charles; Mullis, Kary B.; Westby, Mike; Nizet, Victor

    2015-01-01

    The ever-increasing threat of multi-drug resistant bacterial infections has spurred renewed interest in alternative approaches to classical antibiotic therapy. In contrast to other mammals, humans do not express the galactose-α-1,3-galactosyl-β-1,4-N-acetyl-glucosamine (α-Gal) epitope. As a result of exposure of humans to α-Gal in the environment, a large proportion of circulating antibodies are specific for the trisaccharide. In this study, we examine whether these anti-Gal antibodies can be recruited and redirected to exert anti-bacterial activity. We show that a specific DNA aptamer conjugated to an α-Gal epitope at its 5′ end, herein termed an alphamer, can bind to group A Streptococcus (GAS) bacteria by recognition of a conserved region of the surface-anchored M protein. The anti-GAS alphamer was shown to recruit anti-Gal antibodies to the streptococcal surface in an α-Gal-specific manner, elicit uptake and killing of the bacteria by human phagocytes, and slow growth of invasive GAS in human whole blood. These studies provide a first in vitro proof of concept that alphamers have the potential to redirect pre-existing antibodies to bacteria in a specific manner and trigger an immediate antibacterial immune response. Further validation of this novel therapeutic approach of applying α-Gal technology in in vivo models of bacterial infection is warranted. PMID:25940316

  16. 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.

  17. 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. PMID:23593432

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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. PMID:21667233

  4. Modification of Ad5 Hexon Hypervariable Regions Circumvents Pre-Existing Ad5 Neutralizing Antibodies and Induces Protective Immune Responses

    PubMed Central

    Bruder, Joseph T.; Semenova, Elena; Chen, Ping; Limbach, Keith; Patterson, Noelle B.; Stefaniak, Maureen E.; Konovalova, Svetlana; Thomas, Charlie; Hamilton, Melissa; King, C. Richter; Richie, Thomas L.; Doolan, Denise L.

    2012-01-01

    The development of an effective malaria vaccine is a high global health priority. Vaccine vectors based on adenovirus type 5 are capable of generating robust and protective T cell and antibody responses in animal models and are currently being evaluated in clinical trials for HIV and malaria. They appear to be more effective in terms of inducing antigen-specific immune responses as compared with non-Ad5 serotype vectors. However, the high prevalence of neutralizing antibodies to Ad5 in the human population, particularly in the developing world, has the potential to limit the effectiveness of Ad5-based vaccines. We have generated novel Ad5-based vectors that precisely replace the hexon hypervariable regions with those derived from Ad43, a subgroup D serotype with low prevalence of neutralizing antibody in humans. We have demonstrated that these hexon-modified adenovectors are not neutralized efficiently by Ad5 neutralizing antibodies in vitro using sera from mice, rabbits and human volunteers. We have also generated hexon-modified adenovectors that express a rodent malaria parasite antigen, PyCSP, and demonstrated that they are as immunogenic as an unmodified vector. Furthermore, in contrast to the unmodified vector, the hexon-modified adenovectors induced robust T cell responses in mice with high levels of Ad5 neutralizing antibody. We also show that the hexon-modified vector can be combined with unmodified Ad5 vector in prime-boost regimens to induce protective responses in mice. Our data establish that these hexon-modified vectors are highly immunogenic even in the presence of pre-existing anti-adenovirus antibodies. These hexon-modified adenovectors may have advantages in sub-Saharan Africa where there is a high prevalence of Ad5 neutralizing antibody in the population. PMID:22496772

  5. 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. PMID:27622038

  6. 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

  7. 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.

  8. 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. PMID:11871783

  9. 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. PMID:26626345

  10. Multiple ecthyma gangrenosum in a healthy infant with community-acquired Pseudomonas aeruginosa sepsis.

    PubMed

    Wu, Chang-Teng; Huang, Jing-Long

    2010-10-01

    We report the case of a previously healthy 8-month-old infant girl with Pseudomonas aeruginosa sepsis who presented to a pediatric emergency department with multiple ecthyma gangrenosum. Skin manifestations are uncommon in Pseudomonas infection. Ecthyma gangrenosum is a rare, distinct skin disorder associated with potentially fatal underlying Pseudomonas sepsis. Although typically occurring in immunocompromised or neutropenic patients, it can occasionally affect otherwise healthy children. This case demonstrates the critical importance of the pediatrician's identification of ecthyma gangrenosum to give directed antipseudomonal therapy. PMID:20930597

  11. The role of pre-existing Precambrian structures in rift evolution: The Albertine and Rhino grabens, Uganda

    NASA Astrophysics Data System (ADS)

    Katumwehe, Andrew B.; Abdelsalam, Mohamed G.; Atekwana, Estella A.

    2015-04-01

    We integrated Shuttle Radar Topography Mission (SRTM) Digital Elevation Models (DEM), airborne magnetic, radiometric and three-dimensional Full Tensor Gravity Gradiometry (3D-FTG) data to investigate the role of Precambrian structures in the evolution of the largely amagmatic Miocene-Recent aged Albertine and Rhino grabens in Uganda. These grabens represent the northern segment of the Western Branch of the East African Rift System (EARS). The two NE-trending grabens are connected by a right-stepping transfer zone and they extend within the Archean-Paleoproterozoic Northeast Congo block which represents the northeastern extension of the Congo craton. Our results show the following and highlight the importance of pre-existing structures in the evolution of continental rift systems: (1) The NE-extent of the Albertine full-graben is controlled by NE-trending Precambrian fabric and the graben terminates at its northeastern end when it encounters a multiply folded Precambrian basement terrain with poorly-developed NW-trending structural grain. Additionally, the northeastern termination of the Albertine graben coincides with the presence of NW-trending right-stepping high-density bodies within the Precambrian terrain. (2) The transfer zone between the Albertine and Rhino grabens is controlled by NE-trending Precambrian structures which might have facilitated the development of relay ramp faults. (3) Strain localization within the better-developed southeastern border fault of the Rhino half-graben is facilitated by the presence of Precambrian structures better aligned in a NE-direction in the southeastern part of the basin compared to its northwestern part. (4) Further to the northeast, the Rhino graben is segmented and transitions into a narrower ENE-trending half-graben with a better-developed border fault on its northwestern side. This segmentation coincides with the presence of N-trending Precambrian structures. (5) The Rhino graben terminates farther northeast against

  12. 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

  13. 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. PMID:24863486

  14. Influence of pre-existing inflammation on the outcome of acute coronary syndrome: a cross-sectional study

    PubMed Central

    Odeberg, Jacob; Freitag, Michael; Forssell, Henrik; Vaara, Ivar; Persson, Marie-Louise; Odeberg, Håkan; Halling, Anders; Råstam, Lennart; Lindblad, Ulf

    2016-01-01

    Objectives Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with ACS. Design Cross-sectional study. Setting Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992–1996). Participants In a substudy of Carlscrona Heart Attack Prognosis Study (CHAPS) of 5292 patients admitted to the coronary care unit, we identified 908 patients aged 30–74 years, who at discharge had received the diagnosis of either MI (527) or UA (381). Main outcome measures MI or UA, based on the diagnosis set at discharge from hospital. Results When adjusted for smoking, age, sex and duration of chest pain, concentrations of plasma biomarkers of inflammation (high-sensitivity C reactive protein>2 mg/L (OR=1.40 (1.00 to 1.96) and fibrinogen (p for trend=0.035)) analysed at admission were found to be associated with MI over UA, in an event of ACS. A strong significant association with MI over UA was found for blood cell markers of inflammation, that is, counts of neutrophils (p for trend<0.001), monocytes (p for trend<0.001) and thrombocytes (p for trend=0.021), while lymphocyte count showed no association. Interestingly, eosinophil count (p for trend=0.003) was found to be significantly lower in patients with MI compared to those with UA. Conclusions Our results show that, in patients with ACS, the blood cell profile and degree of inflammation at admission was associated with the outcome. Furthermore, our data suggest that a pre-existing low-grade inflammation may dispose towards MI over UA. PMID:26758266

  15. Ecthyma gangrenosum of the scrotum: a case report.

    PubMed

    Tan, Wei Phin; Sherer, Benjamin A; Hoeksema, Jerome

    2016-03-01

    A 43-year-old man with pancytopenia from chemotherapy for acute myeloid leukemia developed left scrotal pain, fever, and rigors. Physical exam revealed an ulcerating lesion with central necrosis and eschar surrounded by a halo of erythema on the inferior aspect of the left scrotum. The condition indicated an early necrotizing soft tissue infection. The patient was started on broad-spectrum antibiotics and taken to the operating room for a wound debridement. Blood and tissue cultures grew Pseudomonas aeruginosa, which confirmed the diagnosis of ecthyma gangrenosum of the scrotum. The fever resolved, and the wound healed without further progression after wet to dry dressing changes. PMID:26941196

  16. Type-Specific Opsonic Antibodies in Streptococcal Pyoderma

    PubMed Central

    Bisno, Alan L.; Nelson, Kenrad E.

    1974-01-01

    Prospective studies of streptococcal pyoderma were carried out among black children enrolled in Project Headstart centers in Holmes County, Miss. Sera collected from 28 of these children in early October were tested for opsonic antibodies to one of two prevalent skin strains of group A streptococci isolated from them on one or more occasions over the preceding 3 months. The two streptococcal strains (A and B) belong to M-types previously unrecognized. Ten subjects (36%) had antibody to their homologous serotypes detectable by the indirect bactericidal test: this included 6 of 10 subjects infected with strain B but only 4 of 18 infected with strain A (P < 0.05). Of 17 children who had strains A or B isolated from skin lesions only, 12% developed type-specific antibodies (TSA) against the infecting serotype. In contrast, 11 subjects had these strains isolated from throat cultures (either with or without associated pyoderma), and 72% had detectable TSA (P < 0.01). There was no demonstrable relationship between the development of antibodies to streptococcal extracellular products or to non-type-specific cellular antigens and the development of TSA. These results demonstrate that type-specific immune responses do occur following infection with pyoderma streptococci. The frequency with which such antibodies develop is variable and appears related to a number of factors, including the immunologic properties of the infecting strain and the site of bacterial colonization. Pharyngeal carriage may represent an important mechanism for development of acquired immunity to skin strains of group A streptococci. PMID:4435959

  17. 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.

  18. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  19. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  20. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  1. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  2. A dairy-based high calcium diet improves glucose homeostasis and reduces steatosis in the context of pre-existing obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. 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

  4. Perineal reconstruction for severe sequela of ecthyma gangrenosum: report of a case.

    PubMed

    Freud, E; Farkash, U; Prieto, F; Janowski, E; Zer, M

    1999-07-01

    Ecthyma gangrenosum is a cutaneous gangrenous disorder which usually follows Pseudomona aeruginosa infection and is found mainly in immunosuppressed children. We describe a case of a five-year-old female with leukemia with a severe perineal ecthyma gangrenosum resulting in a cloaca-like deformity. One year later a perineoplasty with puborectalis interposition and overlapping external anal sphincteroplasty was successfully performed, achieving satisfactory continence. PMID:10411447

  5. 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

  6. 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

  7. The 3D Numerical Simulation for the Propagation Process of Multiple Pre-existing Flaws in Rock-Like Materials Subjected to Biaxial Compressive Loads

    NASA Astrophysics Data System (ADS)

    Bi, J.; Zhou, X. P.; Qian, Q. H.

    2016-05-01

    General particle dynamics (GPD), which is a novel meshless numerical method, is proposed to simulate the initiation, propagation and coalescence of 3D pre-existing penetrating and embedded flaws under biaxial compression. The failure process for rock-like materials subjected to biaxial compressive loads is investigated using the numerical code GPD3D. Moreover, internal crack evolution processes are successfully simulated using GPD3D. With increasing lateral stress, the secondary cracks keep growing in the samples, while the growth of the wing cracks is restrained. The samples are mainly split into fragments in a shear failure mode under biaxial compression, which is different from the splitting failure of the samples subjected to uniaxial compression. For specimens with macroscopic pre-existing flaws, the simulated types of cracks, the simulated coalescence types and the simulated failure modes are in good agreement with the experimental results.

  8. 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

  9. Ecthyma gangrenosum in a neonate: not always pseudomonas

    PubMed Central

    Pathak, Ashish; Singh, Poonam; Yadav, Yogendra; Dhaneria, Mamta

    2013-01-01

    Ecthyma gangrenosum (EG) is a cutaneous manifestation of invasive infection usually caused by pseudomonas, but can be caused by many bacteria, fungal and viral infections. We present the first reported case of EG caused by invasive Escherichia coli in a neonate. A neonate presented with evidence of sepsis and a rapidly evolving 3×3.5 cm2 well-circumscribed haemorrhagic and necrotic ulcer on the left groin. There was evidence of decreased perfusion of the lower limb owing to pressure effect of the ulcer. The child responded well to anticoagulation and antibiotic therapy. It is crucial to clinically suspect EG and promptly start empiric antibiotic therapy covering pseudomonas to decrease the morbidity and mortality. However, other viruses, fungus and bacteria including E coli should also be considered in the differential diagnosis of EG in a neonate. PMID:23715836

  10. 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