Science.gov

Sample records for pre-existing pyoderma gangrenosum

  1. Vegetative pyoderma gangrenosum.

    PubMed

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

    2014-12-16

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

  2. Sporotrichosis masquerading as pyoderma gangrenosum.

    PubMed

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

    1986-06-01

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

  3. Pyoderma gangrenosum masquerading as Donovanosis

    PubMed Central

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

    2014-01-01

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

  4. Pyoderma Gangrenosum Simulating Necrotizing Fasciitis

    PubMed Central

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

    2015-01-01

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

  5. 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.

  6. Cutaneous blastomycosis masquerading as pyoderma gangrenosum.

    PubMed

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

    2014-04-01

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

  7. Pyoderma gangrenosum induced by episiotomy.

    PubMed

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

    2016-01-19

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

  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 in the Urologist Clinic

    PubMed Central

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

    2016-01-01

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

  10. Pyoderma gangrenosum: A clinician's nightmare

    PubMed Central

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

    2016-01-01

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

  11. 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.

  12. Pyoderma gangrenosum: a systematic review.

    PubMed

    Cozzani, E; Gasparini, G; Parodi, A

    2014-10-01

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

  13. 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

  14. 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

  15. 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.

  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.

  18. Pyoderma gangrenosum following autologous breast reconstruction.

    PubMed

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

    2017-02-01

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

  19. Pyoderma gangrenosum following autologous breast reconstruction

    PubMed Central

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

    2017-01-01

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

  20. [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.

  1. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

    Bryan, Charles S

    2012-01-01

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

  5. Pyoderma gangrenosum after trauma in a dog

    PubMed Central

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

    2016-01-01

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

  6. Diagnosis and management of parastomal pyoderma gangrenosum

    PubMed Central

    Wu, Xian-rui; Shen, Bo

    2013-01-01

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

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

    PubMed

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

    2009-11-01

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

    Mensing, H

    1988-01-01

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

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

    PubMed

    Shenefelt, P D

    1996-05-01

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

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

    PubMed

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

    2002-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. 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.

  15. [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.

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

    PubMed

    Satoh, Masataka; Yamamoto, Toshiyuki

    2013-10-01

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

  17. CD8-positive Mycosis Fungoides Masquerading as Pyoderma Gangrenosum

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-02-23

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

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

    PubMed

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

    2005-01-01

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

  20. [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.

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

    PubMed Central

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

    2017-01-01

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

  2. 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.

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2006-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. 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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed Central

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

    1995-01-01

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

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

    PubMed

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

    2017-02-21

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-02-02

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

  14. 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.

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

    PubMed

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

    2005-03-01

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

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

    PubMed

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

    2000-04-01

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

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

    PubMed

    Omidi, C J; Siegfried, E C

    1998-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2014-01-01

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

  20. [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.

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

    PubMed

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

    1990-02-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    2000-01-01

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

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

    PubMed

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

    2015-02-01

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

  5. 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

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

    PubMed

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

    2011-11-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2017-03-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  15. 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.

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2002-10-01

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

  20. 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.

  1. 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

  2. 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

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

    PubMed

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

    2016-08-17

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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

  6. 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

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2013-02-15

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

  9. 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

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

    PubMed

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

    2017-03-09

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

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

    PubMed

    Odeh, F

    1981-12-15

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

  12. 77 FR 52614 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... HUMAN SERVICES 45 CFR Part 152 RIN 0938-AQ70 Pre-Existing Condition Insurance Plan Program AGENCY... regarding program eligibility to the interim final regulation implementing the Pre- Existing Condition Plan.... (Hereafter, we generally refer to this program as the Pre-Existing Condition Insurance Plan program, or...

  13. Feline pyoderma therapy.

    PubMed

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

    2006-08-01

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

  14. 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.

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

    PubMed

    Luks, A M; Swenson, E R

    2007-04-01

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

  16. 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.

  17. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-01-01

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

  20. Pyoderma Vegetans Misdiagnosed as Verrucous Carcinoma.

    PubMed

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

    2016-02-01

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

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

    PubMed

    Seregin, Sergey S; Amalfitano, Andrea

    2009-12-01

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

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

    ERIC Educational Resources Information Center

    Caza, Arran; Rosch, David M.

    2014-01-01

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

  3. 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…

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  5. 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…

  6. 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.

  7. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2005-11-01

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

  12. 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

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

    PubMed

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

    2009-06-01

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

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

    PubMed Central

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

    2010-01-01

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

  15. 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.

  16. Pyoderma vegetans developed on chronic leg ulcer.

    PubMed

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

    2015-01-01

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

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

    PubMed

    Cerullo, Lauren; Zussman, Jamie; Young, Lorraine

    2009-10-01

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

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

    PubMed

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

    2016-12-07

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

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

    PubMed

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

    2016-09-22

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

  20. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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

  7. 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.

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

    PubMed Central

    Cockerill, Peter N.

    2016-01-01

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

  9. 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.

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

    PubMed

    Kim, David D W; Holdaway, Ian M

    2012-03-01

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

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

    PubMed

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

    2013-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  14. 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).

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

    PubMed

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

    2013-03-01

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

  16. 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.

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

    PubMed

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

    2013-09-01

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

  18. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  19. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

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

    DTIC Science & Technology

    2015-10-01

    The selection theory predicts that pre-existing androgen-independent prostate cancer cells (termed lurker cells ) contribute to CRPC, as they are...AWARD NUMBER: W81XWH-13-1-0470 TITLE: Identification and Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to Castration... Cells that Give Rise to 5a. CONTRACT NUMBER Castration-Resistant Prostate Cancer 5b. GRANT NUMBER W81XWH-13-1-0470 5c. PROGRAM ELEMENT NUMBER 6

  1. 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

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

    PubMed

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

    2017-03-01

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

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

    PubMed

    Kobraei, Kathy B; Wesson, Stanton K

    2010-11-01

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

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

    PubMed

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

    2010-10-01

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

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2008-11-01

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

  7. 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.

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

    PubMed

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

    2014-10-30

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

  9. 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.

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

    PubMed

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

    2012-10-10

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

  11. 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.

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

    PubMed Central

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

    2016-01-01

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

  13. 3D Numerical Modeling of the Propagation of Hydraulic Fracture at Its Intersection with Natural (Pre-existing) Fracture

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  14. 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.

  15. Streptococcus constellatus-associated pyoderma in a dog.

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2016-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  18. 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.

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

    PubMed

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

    2017-01-17

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2010-01-01

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

  2. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. 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.

  6. 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

  7. 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.

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

    PubMed

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

    2011-11-01

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

  9. 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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2009-12-01

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

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

    PubMed

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

    2011-10-01

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

  13. 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.

  14. 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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2006-12-15

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

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

    PubMed

    Wasiak, J; Pohle, T

    1996-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Kang, Zhou-Qing; Zhai, Xiao-Jie

    2015-08-11

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

  2. 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

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    PubMed

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

    2012-12-07

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

  5. 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

  6. 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.

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

    PubMed

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

    2015-01-01

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

  8. 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

  9. 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.

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

    PubMed Central

    Matthews, P B

    1986-01-01

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

  11. 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.

  12. 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

  13. 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

  14. Region-Specific Integration of Embryonic Stem Cell-Derived Neuronal Precursors into a Pre-Existing Neuronal Circuit

    PubMed Central

    Neuser, Franziska; Polack, Martin; Annaheim, Christine; Tucker, Kerry L.; Korte, Martin

    2013-01-01

    Enduring reorganization is accepted as a fundamental process of adult neural plasticity. The most dramatic example of this reorganization is the birth and continuously occurring incorporation of new neurons into the pre-existing network of the adult mammalian hippocampus. Based on this phenomenon we transplanted murine embryonic stem (ES)-cell derived neuronal precursors (ESNPs) into murine organotypic hippocampal slice cultures (OHC) and examined their integration. Using a precise quantitative morphological analysis combined with a detailed electrophysiology, we show a region-specific morphological integration of transplanted ESNPs into different subfields of the hippocampal tissue, resulting in pyramidal neuron-like embryonic stem cell-derived neurons (ESNs) in the Cornu Ammonis (CA1 and CA3) and granule neuron-like ESNs in the dentate gyrus (DG), respectively. Subregion specific structural maturation was accompanied by the development of dendritic spines and the generation of excitatory postsynaptic currents (EPSCs). This cell type specific development does not depend upon NMDA-receptor-dependent synaptic transmission. The presented integration approach was further used to determine the cell-autonomous function of the pan-neurotrophin receptor p75 (P75NTR), as a possible negative regulator of ESN integration. By this means we used p75NTR-deficient ESNPs to study their integration into a WT organotypic environment. We show here that p75NTR is not necessary for integration per se but plays a suppressing role in dendritic development. PMID:23840491

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

    PubMed Central

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

    2009-01-01

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

  16. Blastomycosis-Like Pyoderma- A Rare Case Report

    PubMed Central

    Gejje, Somashekar

    2016-01-01

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

  17. Evaluation of a pre-existing, 3-year household water treatment and handwashing intervention in rural Guatemala

    PubMed Central

    Arnold, Benjamin; Arana, Byron; Mäusezahl, Daniel; Hubbard, Alan; Colford, John M

    2009-01-01

    Background The promotion of household water treatment and handwashing with soap has led to large reductions in child diarrhoea in randomized efficacy trials. Currently, we know little about the health effectiveness of behaviour-based water and hygiene interventions after the conclusion of intervention activities. Methods We present an extension of previously published design (propensity score matching) and analysis (targeted maximum likelihood estimation) methods to evaluate the behavioural and health impacts of a pre-existing but non-randomized intervention (a 3-year, combined household water treatment and handwashing campaign in rural Guatemala). Six months after the intervention, we conducted a cross-sectional cohort study in 30 villages (15 intervention and 15 control) that included 600 households, and 929 children <5 years of age. Results The study design created a sample of intervention and control villages that were comparable across more than 30 potentially confounding characteristics. The intervention led to modest gains in confirmed water treatment behaviour [risk difference = 0.05, 95% confidence interval (CI) 0.02–0.09]. We found, however, no difference between the intervention and control villages in self-reported handwashing behaviour, spot-check hygiene conditions, or the prevalence of child diarrhoea, clinical acute lower respiratory infections or child growth. Conclusions To our knowledge this is the first post-intervention follow-up study of a combined household water treatment and handwashing behaviour change intervention, and the first post-intervention follow-up of either intervention type to include child health measurement. The lack of child health impacts is consistent with unsustained behaviour adoption. Our findings highlight the difficulty of implementing behaviour-based household water treatment and handwashing outside of intensive efficacy trials. PMID:19574492

  18. Evolution of pre-existing versus acquired resistance to platinum drugs and PARP inhibitors in BRCA-associated cancers.

    PubMed

    Yamamoto, Kimiyo N; Hirota, Kouji; Takeda, Shunichi; Haeno, Hiroshi

    2014-01-01

    Platinum drugs and PARP inhibitors ("PARPis") are considered to be effective in BRCA-associated cancers with impaired DNA repair. These agents cause stalled and collapsed replication forks and create double-strand breaks effectively in the absence of repair mechanisms, resulting in arrest of the cell cycle and induction of cell death. However, recent studies have shown failure of these chemotherapeutic agents due to emerging drug resistance. In this study, we developed a stochastic model of BRCA-associated cancer progression in which there are four cancer populations: those with (i) functional BRCA, (ii) dysfunctional BRCA, (iii) functional BRCA and a growth advantage, and (iv) dysfunctional BRCA and a growth advantage. These four cancer populations expand from one cancer cell with normal repair function until the total cell number reaches a detectable amount. We derived formulas for the probability and expected numbers of each population at the time of detection. Furthermore, we extended the model to consider the tumor dynamics during treatment. Results from the model were validated and showed good agreement with clinical and experimental evidence in BRCA-associated cancers. Based on the model, we investigated conditions in which drug resistance during the treatment course originated from either a pre-existing drug-resistant population or a de novo population, due to secondary mutations. Finally, we found that platinum drugs and PARPis were effective if (i) BRCA inactivation is present, (ii) the cancer was diagnosed early, and (iii) tumor growth is rapid. Our results indicate that different types of cancers have a preferential way of acquiring resistance to platinum drugs and PARPis according to their growth and mutational characteristics.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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...

  8. Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome

    PubMed Central

    Ram, Renee R.; Margot, Nicolas A.; Barnes, Tiffany L.; White, Kirsten L.; Callebaut, Christian; Miller, Michael D.

    2017-01-01

    T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1.4%; 47 of 3367 integrase sequences); most often among non-B (5.3%) than B (0.9%) HIV-1 subtypes. During INSTI-based therapy, few patients experienced virologic failure with emergent INSTI RAMs (3%; 122 of 3881 patients), among whom T97A emerged infrequently in the presence (n = 6) or absence (n = 8) of primary INSTI RAMs. A comparison between pre-existing and emergent T97A patient populations (i.e., in the absence of primary INSTI RAMs) showed no significant differences in EVG or RAL susceptibility in vitro. Furthermore, among all T97A-containing viruses tested, only 38–44% exhibited reduced susceptibility to EVG and/or RAL (all of low magnitude; <11-fold), while all maintained susceptibility to dolutegravir. Of the patients with pre-existing T97A, 17 had available clinical follow-up: 16 achieved virologic suppression and 1 maintained T97A and INSTI sensitivity without further resistance development. Overall, T97A is an infrequent integrase polymorphism that is enriched among non-B HIV-1 subtypes and can confer low-level reduced susceptibility to EVG and/or RAL. However, detection of T97A does not affect response to INSTI-based therapy with EVG or RAL. These results suggest a very low risk of initiating INSTI-based therapy in patients with pre-existing T97A. PMID:28212411

  9. 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

  10. Antimicrobial resistance of Staphylococcus pseudintermedius isolates from healthy dogs and dogs affected with pyoderma in Japan.

    PubMed

    Onuma, Kenta; Tanabe, Taishi; Sato, Hisaaki

    2012-02-01

    Staphylococcus pseudintermedius strains were isolated from healthy dogs and dogs with pyoderma in 2000-2002 and 2009. All the isolates from dogs with pyoderma in 1999-2000 and from healthy dogs in 2000-2002 and 2009 were susceptible to cefalexin and/or other cephalosporins and oxacillin. However, 7.1-12.5 and 11.4% of S. pseudintermedius isolates from dogs with pyoderma in 2009 were resistant to cephalosporins and oxacillin, respectively. All S. pseudintermedius isolates from dogs with pyoderma in 1999-2000 and those from healthy dogs in 2000-2002 were susceptible to fluoroquinolones; however, 50% of the S. pseudintermedius strains isolated from dogs with pyoderma in 2009 and 30% of the S. pseudintermedius strains isolated from healthy dogs in 2009 were resistant to fluoroquinolones. Of the 21 oxacillin-resistant S. pseudintermedius (MRSP) isolates, 11 carried SCCmec type V and 10 carried hybrid SCCmec types II-III. Staphylococcus pseudintermedius strains that were resistant to only one of three fluoroquinolones had a mutation in the quinolone resistance determination region of grlA, whereas S. pseudintermedius strains that were resistant to two or more fluoroquinolones had mutations in the quinolone resistance determination regions of both grlA and gyrA.

  11. GAPO syndrome associated with pyoderma vegetans: an unreported co-existence.

    PubMed

    Karadag, A S; Calka, O; Bilgili, S G; Karadag, R; Bulut, G

    2013-01-01

    GAPO syndrome is a rare autosomal recessive disease and an acronym composed of growth retardation, alopecia, pseudoanodontia, optic atrophy. Approximately 38 cases have been reported in literature until now. Pyoderma vegetans is a chronic inflammatory disease characterized with vesicopustular, exudative and vegetative lesions usually localized on face, scalp, axilla and genitalia. Pyoderma vegetans is attributed to a bacterial infection frequently occurring in individuals with an underlying immunosuppressive condition. A 30-year-old female patient was admitted to our clinic with complaint of a hemorrhagic, crusted, exudative vegetative two plaques on the scalp. On her physical examination, she had a prematurely aged face, predominant lower lips, total tooth loss, frontal bossing, enlarged anterior fontanelle, marked scalp veins, micrognatia, depressed nasal bridge, short stature, growth retardation. She was diagnosed as GAPO syndrome as the result of her physical examination. Result of the biopsy taken from scalp was evaluated as pyoderma vegetans. And the diagnosis of pyoderma vegetans was established based on the correlate of both clinical and histopathologic findings. Pyoderma vegetans coexisting with GAPO syndrome has not been reported previously. Thus we wished to report it.

  12. Pyoderma vegetans of the posterior area of the neck: case presentation.

    PubMed

    Meşină, Cristian; Vasile, Ion; Mogoantă, Stelian Ştefăniţă; Ciurea, Marius Eugen; Pârvănescu, Horia; Dumitrescu, Theodor Viorel; Georgescu, Claudia Valentina; Ciobanu, Daniela

    2015-01-01

    Pyoderma vegetans is a rare disease characterized by the presence of vegetant exudative, pustular and erythematous vesiculobullous plaque usually located in the inguinal area and axillary fold. Etiology of pyoderma vegetans is unknown but it is often associated with bacterial infections in immunocompromised patients. Main histopathological characteristics of pyoderma crops are pseudoepitheliomatous hyperplasia and subepidermal, intraepidermal neutrophilic or eosinophilic microabscesses. It is well known that these lesions are commonly associated with colonic inflammatory disease such as ulcerative colitis and Crohn's disease. Not available standard treatment for pyoderma vegetans, although the use of antibiotic therapy was often used with variable results. Standard first-line therapy is the systemic steroids yet. We perform excision of the lesion of the posterior area of the neck with application of the free split-thickness skin graft after 48 hours postoperatively. In this paper, we present a case of pyoderma vegetans with unusual location without associating colonic lesions and a review of literature related to therapeutic and diagnostic problems of this disease.

  13. Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing

    PubMed Central

    Takeda, Haruhiko; Ueda, Yoshihide; Inuzuka, Tadashi; Yamashita, Yukitaka; Osaki, Yukio; Nasu, Akihiro; Umeda, Makoto; Takemura, Ryo; Seno, Hiroshi; Sekine, Akihiro; Marusawa, Hiroyuki

    2017-01-01

    Resistance-associated variant (RAV) is one of the most significant clinical challenges in treating HCV-infected patients with direct-acting antivirals (DAAs). We investigated the viral dynamics in patients receiving DAAs using third-generation sequencing technology. Among 283 patients with genotype-1b HCV receiving daclatasvir + asunaprevir (DCV/ASV), 32 (11.3%) failed to achieve sustained virological response (SVR). Conventional ultra-deep sequencing of HCV genome was performed in 104 patients (32 non-SVR, 72 SVR), and detected representative RAVs in all non-SVR patients at baseline, including Y93H in 28 (87.5%). Long contiguous sequences spanning NS3 to NS5A regions of each viral clone in 12 sera from 6 representative non-SVR patients were determined by third-generation sequencing, and showed the concurrent presence of several synonymous mutations linked to resistance-associated substitutions in a subpopulation of pre-existing RAVs and dominant isolates at treatment failure. Phylogenetic analyses revealed close genetic distances between pre-existing RAVs and dominant RAVs at treatment failure. In addition, multiple drug-resistant mutations developed on pre-existing RAVs after DCV/ASV in all non-SVR cases. In conclusion, multi-drug resistant viral clones at treatment failure certainly originated from a subpopulation of pre-existing RAVs in HCV-infected patients. Those RAVs were selected for and became dominant with the acquisition of multiple resistance-associated substitutions under DAA treatment pressure. PMID:28361915

  14. 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

  15. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion.

    PubMed

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth.

  16. Temperature-Dependent Structural Changes of Parkinson's Alpha-Synuclein Reveal the Role of Pre-Existing Oligomers in Alpha-Synuclein Fibrillization

    PubMed Central

    Ariesandi, Winny; Chang, Chi-Fon; Chen, Tseng-Erh; Chen, Yun-Ru

    2013-01-01

    Amyloid fibrils of α-synuclein are the main constituent of Lewy bodies deposited in substantial nigra of Parkinson's disease brains. α-Synuclein is an intrinsically disordered protein lacking compact secondary and tertiary structures. To enhance the understanding of its structure and function relationship, we utilized temperature treatment to study α-synuclein conformational changes and the subsequent effects. We found that after 1 hr of high temperature pretreatment, >80°C, α-synuclein fibrillization was significantly inhibited. However, the temperature melting coupled with circular dichroism spectra showed that α-synuclein was fully reversible and the NMR studies showed no observable structural changes of α-synuclein after 95°C treatment. By using cross-linking and analytical ultracentrifugation, rare amount of pre-existing α-synuclein oligomers were found to decrease after the high temperature treatment. In addition, a small portion of C-terminal truncation of α-synuclein also occurred. The reduction of pre-existing oligomers of α-synuclein may contribute to less seeding effect that retards the kinetics of amyloid fibrillization. Overall, our results showed that the pre-existing oligomeric species is a key factor contributing to α-synuclein fibrillization. Our results facilitate the understanding of α-synuclein fibrillization. PMID:23349712

  17. Blastomycosis-like pyoderma in association with recurrent vesicular hand eczema: good response to acitretin.

    PubMed

    Cecchi, Roberto; Bartoli, Laura; Brunetti, Luigi; Pavesi, Mario

    2011-03-15

    Blastomycosis-like pyoderma, also known as pyoderma vegetans, is an uncommon disease characterized by vegetating skin lesions mimicking blastomycosis or warty tuberculosis, often associated with staphylococcal and streptococcal infections. It is more commonly observed in elderly patients with impaired immunological capacity, and is often unresponsive to various therapeutic modalities. We describe a case of BLP that occurred on the palmar aspect of the left hand in an elderly female, affected with recurrent vesicular hand eczema. The disease resolved completely following the administration of oral acitretin 25 mg/day for 10 weeks.

  18. Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre-existing chronic kidney disease.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Hashimoto, Yasunobu; Yoshida, Kazuhiko; Tanabe, Kazunari

    2014-06-01

    We compared kidney functional recovery between patients with pre-existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre-existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: -6.8%, group 2: -18%, group 3: -7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: -0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre-existing chronic kidney

  19. The effects of pre-existing discontinuities on the surface expression of normal faults: Insights from wet-clay analog modeling

    NASA Astrophysics Data System (ADS)

    Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Burrato, Pierfrancesco; Seno, Silvio; Valensise, Gianluca

    2016-08-01

    We use wet-clay analog models to investigate how pre-existing discontinuities (i.e. structures inherited from previous tectonic phases) affect the evolution of a normal fault at the Earth's surface. To this end we first perform a series of three reference experiments driven by a 45° dipping master fault unaffected by pre-existing discontinuities to generate a mechanically isotropic learning set of models. We then replicate the experiment six times introducing a 60°-dipping precut in the clay cake, each time with a different attitude and orientation with respect to an initially-blind, 45°-dipping, master normal fault. In all experiments the precut intersects the vertical projection of the master fault halfway between the center and the right-hand lateral tip. All other conditions are identical for all seven models. By comparing the results obtained from the mechanically isotropic experiments with results from experiments with precuts we find that the surface evolution of the normal fault varies depending on the precut orientation. In most cases the parameters of newly-forming faults are strongly influenced. The largest influence is exerted by synthetic and antithetic discontinuities trending respectively at 30° and 45° from the strike of the master fault, whereas a synthetic discontinuity at 60° and an antithetic discontinuity at 30° show moderate influence. Little influence is exerted by a synthetic discontinuity at 45° and an antithetic discontinuity at 60° from the strike of the master fault. We provide a ranking chart to assess fault-to-discontinuity interactions with respect to essential surface fault descriptors, such as segmentation, vertical-displacement profile, maximum displacement, and length, often used as proxies to infer fault properties at depth. Considering a single descriptor, the amount of deviation induced by different precuts varies from case to case in a rather unpredictable fashion. Multiple observables should be taken into

  20. High Frequency of Pre-Existing Type 2 Diabetes in a Series of Pregnant Women Referred for "Gestational Diabetes" in a Large Canadian Indigenous Community.

    PubMed

    Toth, Ellen L; Keith, Kristin-Lee; Littlechild, Randy; Myskiw, Joy; Meneen, Kari; Buckreus, Kelli; Oster, Richard T

    2016-12-01

    We examined the referral processes and true diagnostic classifications for diabetes complicating pregnancy in a series of 62 pregnant women consecutively referred to a diabetes education and treatment centre in a large Indigenous community in Alberta, Canada. The referrals were made over a 5-year period (2010 to 2015). The main findings of this analysis were the high frequency (38.7%) of pre-existing type 2 diabetes and previously undiagnosed or unrecognized overt diabetes and the deficiencies in early testing and recognition.

  1. A case of methicillin-resistant Staphylococcus pseudintermedius (MRSP) pyoderma in a Labrador retriever dog.

    PubMed

    Wan, Jennifer

    2014-11-01

    An 8-year-old, neutered male Labrador retriever dog with generalized pruritis had a history of recurring atopic dermatitis and superficial pyoderma. Cocci and yeast were found on cytology and methicillin-resistant Staphylococcus pseudintermedius was cultured. A regimen of marbofloxacin, dexamethasone, ketoconazole, and cyclosporine in addition to bathing with 2% chlorhexidine shampoo resulted in marked improvement.

  2. A case of methicillin-resistant Staphylococcus pseudintermedius (MRSP) pyoderma in a Labrador retriever dog

    PubMed Central

    Wan, Jennifer

    2014-01-01

    An 8-year-old, neutered male Labrador retriever dog with generalized pruritis had a history of recurring atopic dermatitis and superficial pyoderma. Cocci and yeast were found on cytology and methicillin-resistant Staphylococcus pseudintermedius was cultured. A regimen of marbofloxacin, dexamethasone, ketoconazole, and cyclosporine in addition to bathing with 2% chlorhexidine shampoo resulted in marked improvement. PMID:25392557

  3. Efficacy of a surgical scrub including 2% chlorhexidine acetate for canine superficial pyoderma.

    PubMed

    Murayama, Nobuo; Nagata, Masahiko; Terada, Yuri; Shibata, Sanae; Fukata, Tsuneo

    2010-12-01

    The clinical efficacy of a surgical scrub containing 2% chlorhexidine acetate (2CA; Nolvasan® Surgical Scrub; Fort Dodge Animal Health, USA) was evaluated for the topical management of canine superficial pyoderma. The first study was a randomized, double-blind, controlled trial. The control was a shampoo containing 4% chlorhexidine gluconate (4CG; Skin Clinic Shampoo; CHD MEDICS, Goyang, Korea). Ten dogs with symmetrical lesions of canine superficial pyoderma were allocated to receive either 2CA or the control shampoo applied to either side of the body twice weekly for 1 week. Both the owners and the investigators subjectively scored skin lesions including pruritus, erythema, crusted papules and scales on a scale of 0-3. The 2CA and 4CG resulted in almost the same degree of improvement of skin lesions, and there were no significant differences between the two groups. The second study was an open trial of 2CA monotherapy in eight dogs with cefalexin-resistant Staphylococcus intermedius group-associated superficial pyoderma. The 2CA monotherapy was applied every 2 days for 2 weeks. Five dogs improved with 2CA monotherapy, one partially improved and two did not. No adverse reactions were seen in either trial. This suggests that a 2CA surgical scrub could be a useful and safe topical adjunct therapy for dogs with superficial pyoderma involving cefalexin-resistant Staphylococcus intermedius group.

  4. Cladodes, leaf-like organs in Asparagus, show the significance of co-option of pre-existing genetic regulatory circuit for morphological diversity of plants.

    PubMed

    Nakayama, Hokuto; Yamaguchi, Takahiro; Tsukaya, Hirokazu

    2012-08-01

    Plants in the genus Asparagus have determinate leaf-like organs called cladodes in the position of leaf axils. Because of their leaf-like morphology, axillary position, and morphological variation, it has been unclear how this unusual organ has evolved and diversified. In the previous study, we have shown that cladodes in the genus Asparagus are modified axillary shoots and proposed a model that cladodes have arisen by co-option and deployment of genetic regulatory circuit (GRC) involved in leaf development. Moreover, we proposed that the alteration of the expression pattern of genes involved in establishment of adaxial/abaxial polarity has led to the morphological diversification from leaf-like to rod-like form of cladodes in the genus. Thus, these results indicated that the co-option and alteration of pre-existing GRC play an important role in acquisition and subsequent morphological diversification. Here, we present data of further expression analysis of A. asparagoides. The results suggested that only a part of the GRC involved in leaf development appears to have been co-opted into cladode development. Based on our study and several examples of the morphological diversification, we briefly discuss the importance of co-option of pre-existing GRC and its genetic modularity in the morphological diversity of plants during evolution.

  5. Pre-existing oblique transfer zones and transfer/transform relationships in continental margins: New insights from the southeastern Gulf of Aden, Socotra Island, Yemen

    NASA Astrophysics Data System (ADS)

    Bellahsen, N.; Leroy, S.; Autin, J.; Razin, P.; d'Acremont, E.; Sloan, H.; Pik, R.; Ahmed, A.; Khanbari, K.

    2013-11-01

    Transfer zones are ubiquitous features in continental rifts and margins, as are transform faults in oceanic lithosphere. Here, we present a structural study of the Hadibo Transfer Zone (HTZ), located in Socotra Island (Yemen) in the southeastern Gulf of Aden. There, we interpret this continental transfer fault zone to represent a reactivated pre-existing structure. Its trend is oblique to the direction of divergence and it has been active from the early up to the latest stages of rifting. One of the main oceanic fracture zones (FZ), the Hadibo-Sharbithat FZ, is aligned with and appears to be an extension of the HTZ and is probably genetically linked to it. Comparing this setting with observations from other Afro-Arabian rifts as well as with passive margins worldwide, it appears that many continental transfer zones are reactivated pre-existing structures, oblique to divergence. We therefore establish a classification system for oceanic FZ based upon their relationship with syn-rift structures. Type 1 FZ form at syn-rift structures and are late syn-rift to early syn-OCT. Type 2 FZ form during the OCT formation and Type 3 FZ form within the oceanic domain, after the oceanic spreading onset. The latter are controlled by far-field forces, magmatic processes, spreading rates, and oceanic crust rheology.

  6. Lack of efficacy of pre bronchoscopy inhaled salbutamol on symptoms and lung functions in patients with pre-existing airway obstruction

    PubMed Central

    Mohan, Anant; Momin, Indrajit; Poulose, Rosemary; Mohan, Charu; Madan, Karan; Hadda, Vijay; Guleria, Randeep; Pandey, RM

    2016-01-01

    Background: Fiberoptic bronchoscopy (FOB) may exaggerate symptoms and lung functions in patients with pre-existing airway obstruction. Interventions which can alleviate or minimize this procedure-related bronchospasm, especially in this high-risk group are, therefore, required. Methods: A double-blinded randomized controlled trial was conducted to evaluate the efficacy of 400 μg of inhaled salbutamol on patients with spirometric evidence of airflow obstruction planned for FOB. Patient's dyspnea, procedure tolerability, and change in spirometry were assessed before and after the procedure. Results: A total of 50 patients were enrolled (78% males), with a mean (standard deviation) age of 49.8 (6.2) years. There was a significant fall in % predicted FEV1 within each group compared to their respective pre-bronchoscopy values. However, no significant difference in the % predicted or absolute FEV1 level was observed between the two groups. Similarly, although both groups experienced increased dyspnea immediately following FOB, this difference was not significant between the two groups either on the Borg or visual analog scale scales. Pre-FOB anxiety levels and the tolerability of the procedure as assessed by the bronchoscopist were similar in both groups. Conclusion: FOB in patients with pre-existing airway obstruction aggravates cough and dyspnea, with a concomitant decline in FEV1 and FVC. The administration of pre-FOB inhaled salbutamol does not have any significant beneficial effect on procedure-related outcomes. PMID:27578926

  7. Reduction in Noise-Induced Functional Loss of the Cochleae in Mice with Pre-Existing Cochlear Dysfunction Due to Genetic Interference of Prestin

    PubMed Central

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation. PMID:25486270

  8. Increased CD8+ T cell memory to concurrent infection at the expense of increased erosion of pre-existing memory: the paradoxical role of IL-15.

    PubMed

    Chapdelaine, Yvan; Smith, Dean K; Pedras-Vasconcelos, Joao A; Krishnan, Lakshmi; Sad, Subash

    2003-11-15

    The use of cytokines during vaccination, particularly IL-15, is being considered due to the unique ability of IL-15 to enhance the proliferation of memory CD8(+) T cells. However, as homeostatic mechanisms limit excessive lymphocyte expansion, we addressed the consequences of this enhancement of T cell memory by IL-15. Infection of mice with either recombinant Mycobacterium bovis (BCG) expressing IL-15 (BCG-IL-15) or BCG and purified IL-15 resulted in an increased CD44, IL-2Rbeta expression and increased frequency of IFN-gamma-secreting CD8(+) T cells. Surprisingly, the enhancement of memory to concurrent infection by IL-15 exacerbated the attrition of pre-existing memory. Infection of mice with Listeria monocytogenes expressing OVA resulted in potent OVA(257-264)-specific CD8(+) T cell memory, and a challenge of these mice with either BCG-IL-15 or BCG and purified IL-15 resulted in an increased erosion of OVA(257-264)-specific CD8(+) T cell memory, relative to BCG. Enhancement in the erosion of OVA-specific CD8(+) T cell memory by BCG-IL-15 resulted in a consequently greater impairment in protection against a challenge with OVA-expressing tumor cells. We thus raise important questions regarding vaccinations that are aimed at maximizing T cell memory without considering the impact on pre-existing T cell memory.

  9. Reduction in noise-induced functional loss of the cochleae in mice with pre-existing cochlear dysfunction due to genetic interference of prestin.

    PubMed

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation.

  10. Reactivation of compressional pre-existing structures in an extensional regime by wastewater re-injection induced seismicity: a Southern Appennine (Italy) oilfield case study

    NASA Astrophysics Data System (ADS)

    Buttinelli, M.; Improta, L.; Bagh, S.; Chiarabba, C.

    2015-12-01

    The Val d'Agri Quaternary basin is located within the Southern Apennine extensional belt, hosting the largest oilfield in Europe. Since 2006 wastewaters coming from oil production were re-injected by a single disposal well into the reservoir, represented by the carbonates of the Apulian platform. Consequently, induced micro-seismicity (219 events, ML < 2.3) was recorded close to the beginning of injection and within 5 km of the well. Afterwards, a detailed analysis of the oilfield underground dataset was performed to define a 3D geological model of the injection site. A pre-existing thrust system inherited by a Plio-Pleistocene compressional tectonic phase mainly constituted by NE-verging high-angle thrusts and SW-verging back-thrusts interesting the Apulian carbonates was interpreted. Below the injection well a mainly E-dipping back-thrust completely developed between two major thrusts can be modeled. The depth conversions of seismic interpretation based on sonic logs, VSP and seismic check-shots highlighted that the back-thrust geometry is compatible with accurate 3D absolute location and high precision relative location of induced events. Such analysis also show that wastewater injection firstly caused the reactivation of the deep portion of the back-thrust, and then seismicity mainly migrated up-dip toward shallower depths and interesting some portions of other faults, but remaining almost confined within the reservoir volume, and close to the injection well. These combined results also suggest that induced events presumably occurred on a small and high-permeability patch of the fault zone, favorably oriented with respect to the present-day SW-NE trending extensional stress field. Results can be read in the light of understanding the impact that induced seismicity due to the reactivation of pre-existing/inactive faults might have on seismic hazard and seismogenic potential evaluations, especially in tectonically active areas like Italy

  11. A distinct pre-existing inflammatory tumour microenvironment is associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer

    PubMed Central

    Koti, M; Siu, A; Clément, I; Bidarimath, M; Turashvili, G; Edwards, A; Rahimi, K; Masson, A-M M; Squire, J A

    2015-01-01

    Background: Chemotherapy resistance is a major determinant of poor overall survival rates in high-grade serous ovarian cancer (HGSC). We have previously shown that gene expression alterations affecting the NF-κB pathway characterise chemotherapy resistance in HGSC, suggesting that the regulation of an immune response may be associated with this phenotype. Methods: Given that intrinsic drug resistance pre-exists and is governed by both tumour and host factors, the current study was performed to examine the cross-talk between tumour inflammatory microenvironment and cancer cells, and their roles in mediating differential chemotherapy response in HGSC patients. Expression profiling of a panel of 184 inflammation-related genes was performed in 15 chemoresistant and 19 chemosensitive HGSC tumours using the NanoString nCounter platform. Results: A total of 11 significantly differentially expressed genes were found to distinguish the two groups. As STAT1 was the most significantly differentially expressed gene (P=0.003), we validated the expression of STAT1 protein by immunohistochemistry using an independent cohort of 183 (52 resistant and 131 sensitive) HGSC cases on a primary tumour tissue microarray. Relative expression levels were subjected to Kaplan–Meier survival analysis and Cox proportional hazard regression models. Conclusions: This study confirms that higher STAT1 expression is significantly associated with increased progression-free survival and that this protein together with other mediators of tumour–host microenvironment can be applied as a novel response predictive biomarker in HGSC. Furthermore, an overall underactive immune microenvironment suggests that the pre-existing state of the tumour immune microenvironment could determine response to chemotherapy in HGSC. PMID:25826225

  12. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    PubMed

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes; Bassi, Maria Rosaria; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2012-01-01

    Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  13. Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid Leukemia

    PubMed Central

    Skaggs, Brian; Gorre, Mercedes; Sawyers, Charles L.; Michor, Franziska

    2011-01-01

    Chronic myeloid leukemia (CML) is the first human malignancy to be successfully treated with a small molecule inhibitor, imatinib, targeting a mutant oncoprotein (BCR-ABL). Despite its successes, acquired resistance to imatinib leads to reduced drug efficacy and frequent progression of disease. Understanding the characteristics of pre-existing resistant cells is important for evaluating the benefits of first-line combination therapy with second generation inhibitors. However, due to limitations of assay sensitivity, determining the existence and characteristics of resistant cell clones at the start of therapy is difficult. Here we combined a mathematical modeling approach using branching processes with experimental data on the fitness changes (i.e., changes in net reproductive rate) conferred by BCR-ABL kinase domain mutations to investigate the likelihood, composition, and diversity of pre-existing resistance. Furthermore, we studied the impact of these factors on the response to tyrosine kinase inhibitors. Our approach predicts that in most patients, there is at most one resistant clone present at the time of diagnosis of their disease. Interestingly, patients are no more likely to harbor the most aggressive, pan-resistant T315I mutation than any other resistance mutation; however, T315I cells on average establish larger-sized clones at the time of diagnosis. We established that for patients diagnosed late, the relative benefit of combination therapy over monotherapy with imatinib is significant, while this benefit is modest for patients with a typically early diagnosis time. These findings, after pre-clinical validation, will have implications for the clinical management of CML: we recommend that patients with advanced-phase disease be treated with combination therapy with at least two tyrosine kinase inhibitors. PMID:22140458

  14. Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine.

    PubMed

    Chuan, Yap P; Rivera-Hernandez, Tania; Wibowo, Nani; Connors, Natalie K; Wu, Yang; Hughes, Fiona K; Lua, Linda H L; Middelberg, Anton P J

    2013-09-01

    Modularization of a peptide antigen for presentation on a microbially synthesized murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative for rapid and low-cost vaccine delivery at a global scale. In this approach, heterologous modules containing peptide antigenic elements are fused to and displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via ordered and densely repeated presentation of the modules. This study addresses two key engineering questions pertaining to this platform, exploring the effects of (i) pre-existing carrier-specific immunity on modular VLP vaccine effectiveness and (ii) increase in the antigenic element number per VLP on peptide-specific immune response. These effects were studied in a mouse model and with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen, J8i. The data presented here demonstrate that immunization with a modular VLP could induce high levels of J8i-specific antibodies despite a strong pre-existing anti-carrier immune response. Doubling of the J8i antigenic element number per VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the strategy, when used in conjunction with increased VLP dose, could effectively increase the peptide dose up to 10-fold, leading to a significantly higher J8i-specific antibody titer. This study further supports feasibility of the MuPyV modular VLP vaccine platform by showing that, in the absence of adjuvant, modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to raise a high level of peptide-specific IgGs indicative of bactericidal activity.

  15. Early Colonoscopy Confers Survival Benefits on Colon Cancer Patients with Pre-Existing Iron Deficiency Anemia: A Nationwide Population-Based Study

    PubMed Central

    Teng, Chieh-Lin Jerry; Yu, Jui-Ting; Chen, Yi-Huei; Lin, Ching-Heng; Hwang, Wen-Li

    2014-01-01

    This study aimed to examine the prognostic significance of pre-existing iron deficiency anemia (IDA) and the benefits of early colonoscopy in patients with colon cancer, since these have not been clearly established to date. Using the Taiwanese National Health Insurance Research Database, we retrieved and retrospectively reviewed the records of patients aged ≥55 years who were diagnosed with colon cancer between 2000 and 2005. The patient cohort was divided into two groups: patients with (n = 1,260) or without (n = 15,912) an IDA diagnosis during ≤18 months preceding the date of colon cancer diagnosis. We found that diabetes (27.9% vs. 20.3%, p<0.0001), cardiovascular disease (61.6% vs. 54.7%, p<0.001), and chronic kidney disease (4.6% vs. 2.2%, p<0.0001) were more common among patients with IDA than among those without IDA. The median overall survival times for patients with IDA and those without IDA were 4.6 and 5.7 years, respectively (p = 0.002). Patients who underwent colonoscopy ≤30 days, 31–90, and ≥91 days after IDA diagnosis showed median overall survival times of 5.79, 4.43, and 4.04 years, respectively (p = 0.003). Delayed colonoscopy was an independent factor associated with poor overall survival (adjusted hazard ratio, 1.28; 95% confidence interval, 1.07–1.53; p = 0.01). In conclusion, colon cancer patients with IDA were more likely to experience comorbidities than were those without IDA. Pre-existing IDA was a poor prognostic factor in adult men and postmenopausal women who had colon cancer. Early colonoscopy could improve overall survival possibly by facilitating early diagnosis and treatment. PMID:24466209

  16. Early colonoscopy confers survival benefits on colon cancer patients with pre-existing iron deficiency anemia: a nationwide population-based study.

    PubMed

    Teng, Chieh-Lin Jerry; Yu, Jui-Ting; Chen, Yi-Huei; Lin, Ching-Heng; Hwang, Wen-Li

    2014-01-01

    This study aimed to examine the prognostic significance of pre-existing iron deficiency anemia (IDA) and the benefits of early colonoscopy in patients with colon cancer, since these have not been clearly established to date. Using the Taiwanese National Health Insurance Research Database, we retrieved and retrospectively reviewed the records of patients aged ≥ 55 years who were diagnosed with colon cancer between 2000 and 2005. The patient cohort was divided into two groups: patients with (n = 1,260) or without (n = 15,912) an IDA diagnosis during ≤ 18 months preceding the date of colon cancer diagnosis. We found that diabetes (27.9% vs. 20.3%, p<0.0001), cardiovascular disease (61.6% vs. 54.7%, p<0.001), and chronic kidney disease (4.6% vs. 2.2%, p<0.0001) were more common among patients with IDA than among those without IDA. The median overall survival times for patients with IDA and those without IDA were 4.6 and 5.7 years, respectively (p = 0.002). Patients who underwent colonoscopy ≤ 30 days, 31-90, and ≥ 91 days after IDA diagnosis showed median overall survival times of 5.79, 4.43, and 4.04 years, respectively (p = 0.003). Delayed colonoscopy was an independent factor associated with poor overall survival (adjusted hazard ratio, 1.28; 95% confidence interval, 1.07-1.53; p = 0.01). In conclusion, colon cancer patients with IDA were more likely to experience comorbidities than were those without IDA. Pre-existing IDA was a poor prognostic factor in adult men and postmenopausal women who had colon cancer. Early colonoscopy could improve overall survival possibly by facilitating early diagnosis and treatment.

  17. Ecthyma gangrenosum in a 3-month-old, previously healthy infant

    PubMed Central

    Zhang, Xiao-ting; Jin, Wan-wan; Ma, Xin-hua; Yu, Hai-feng; Tang, Xu-hua

    2017-01-01

    Abstract Rationale: Ecthyma gangrenosum (EG) is an aggressive cutaneous disease caused by local or systemic infection with Pseudomonas aeruginosa. EG is characterized by cutaneous manifestations ranging from nodule and papule, to necrotic ulceration with surrounding erythema, especially with black eschar or central crust. EG presents with characteristic skin lesions which is important to establish diagnosis of sepsis caused by P aeruginosa, a serious condition that can be treated efficiently if diagnosed early. Patient concerns: A 3-month-old female infant was presented with characteristic skin lesions of EG and developed sepsis 3 days later. Diagnoses: Ecthyma gangrenosum and sepsis caused by Pseudomonas aeruginosa. Interventions: Meropenem was used in combination with ceftazidime at first and excision of necrotic skin lesions was performed later. Outcomes: Cure. Lessons: Early recognition of EG plays an important role in providing appropriate empiric antibiotic treatment at early stage of sepsis, and improves the prognosis. Surgical excision may be helpful if no improvement was achieved via antibiotic treatment. PMID:28272221

  18. Scrum kidney: epidemic pyoderma caused by a nephritogenic Streptococcus pyogenes in a rugby team.

    PubMed

    Ludlam, H; Cookson, B

    1986-08-09

    In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match.

  19. [Effect of imunofan on several indexes of immunity and pyoderma incidence among cadets of educational institutes].

    PubMed

    Mar'in, G G; Akimkin, V G; Novikov, V A; Tutel'ian, A V; Stepanov, O G; Kornilov, A B; Salmina, T A

    2009-09-01

    It was discovered that during the first several months military service men have suppression of several indexes of immunity and a high level of morbidity by pyoderma. Was shown a high effectiveness of immunomodulatory agent Imunofan on correction of immunity status of servicemen and decrease of morbidity by pyoderma (more than on threefold): the effectiveness index is 3,25, the defense index is 69,2%. In addition, it was marked hepatitis- and stress-protect effect of the agent. It was made a conclusion about necessity of further examination of questions of correction of immunity status of military servicemen for the purpose of decrease of morbidity by infections, actual for studying units of the Armed Forces of RF.

  20. The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma

    PubMed Central

    Bowen, Asha C.; Mahé, Antoine; Hay, Roderick J.; Andrews, Ross M.; Steer, Andrew C.; Tong, Steven Y. C.; Carapetis, Jonathan R.

    2015-01-01

    Objective We conducted a comprehensive, systematic review of the global childhood population prevalence of impetigo and the broader condition pyoderma. Methods PubMed was systematically searched for impetigo or pyoderma studies published between January 1 1970 and September 30 2014. Two independent reviewers extracted data from each relevant article on the prevalence of impetigo. Findings Sixty-six articles relating to 89 studies met our inclusion criteria. Based on population surveillance, 82 studies included data on 145,028 children assessed for pyoderma or impetigo. Median childhood prevalence was 12·3% (IQR 4·2–19·4%). Fifty-eight (65%) studies were from low or low-middle income countries, where median childhood prevalences were 8·4% (IQR 4·2–16·1%) and 14·5% (IQR 8·3–20·9%), respectively. However, the highest burden was seen in underprivileged children from marginalised communities of high-income countries; median prevalence 19·4%, (IQR 3·9–43·3%). Conclusion Based on data from studies published since 2000 from low and low-middle income countries, we estimate the global population of children suffering from impetigo at any one time to be in excess of 162 million, predominantly in tropical, resource-poor contexts. Impetigo is an under-recognised disease and in conjunction with scabies, comprises a major childhood dermatological condition with potential lifelong consequences if untreated. PMID:26317533

  1. Pyoderma Gangrenosum–Like Ulcer in a Patient With X-Linked Agammaglobulinemia

    PubMed Central

    Murray, Patrick R.; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B.; Ecker, David J.; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L.

    2011-01-01

    Background Pyoderma gangrenosum–like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient’s culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. Observation An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when sub-cultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. Conclusions This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum–like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum–like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy. PMID:20479300

  2. Antimicrobial susceptibility profiles of Staphylococcus intermedius isolates from clinical cases of canine pyoderma in South Africa.

    PubMed

    Blunt, Catherine A; van Vuuren, Moritz; Picard, Jacqueline

    2013-05-16

    Successful treatment of canine pyoderma has become compromised owing to the development of antimicrobial resistance with accompanying recurrence of infection. Canine skin samples submitted to a veterinary diagnostic laboratory for microbiological culture and sensitivity between January 2007 and June 2010, from which Staphylococcus intermedius was isolated, were selected for this investigation. Antimicrobial resistance of S. intermedius was most prevalent with reference to ampicillin followed by resistance to tetracycline and then potentiated sulphonamides. In general, antimicrobial resistance was low and very few methicillin-resistant isolates were detected. Temporal trends were not noted, except for ampicillin, with isolates becoming more susceptible, and potentiated sulphonamides (co-trimoxazole), with isolates becoming more resistant. In general, both the Kirby-Bauer disc diffusion and broth dilution minimum inhibitory concentration tests yielded similar results for the antimicrobial agents tested. The main difference was evident in the over-estimation of resistance by the Kirby-Bauer test for ampicillin, co-trimoxazole, penicillin and doxycycline. Knowledge of trends in bacterial resistance is important for veterinarians when presented with canine pyoderma. Analysis of antimicrobial susceptibility profiles of S. intermedius isolated from canine pyodermas will guide veterinarians' use of the most appropriate agent and encourage prudent use of antimicrobials in companion animals.

  3. An XML model of an enhanced data dictionary to facilitate the exchange of pre-existing clinical research data in international studies.

    PubMed

    Duda, Stephany N; Cushman, Clint; Masys, Daniel R

    2007-01-01

    Pre-existing clinical research data sets exchanged in international epidemiology research often lack the elements needed to assess their suitability for use in multi-region meta-analyses or other clinical studies. While the missing information is generally known to local investigators, it is not contained in the files exchanged between sites. Instead, such content must be solicited by the study coordinating center though a series of lengthy phone and electronic communications: an informal process whose reproducibility and accuracy decays over time. This report describes a set of supplemental information needed to assess whether clinical research data from diverse research sites are truly comparable, and what metadata ("data about the data") should be preserved when a data set is archived for future use. We propose a structured Extensible Markup Language (XML) model that captures this information. The authors hope this model will be a first step towards preserving the metadata associated with clinical research data sets, thereby improving the quality of international data exchange, data archiving, and merged-data research using data collected in many different countries, languages and care settings.

  4. An Analytical Model for Assessing Stability of Pre-Existing Faults in Caprock Caused by Fluid Injection and Extraction in a Reservoir

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Bai, Bing; Li, Xiaochun; Liu, Mingze; Wu, Haiqing; Hu, Shaobin

    2016-07-01

    Induced seismicity and fault reactivation associated with fluid injection and depletion were reported in hydrocarbon, geothermal, and waste fluid injection fields worldwide. Here, we establish an analytical model to assess fault reactivation surrounding a reservoir during fluid injection and extraction that considers the stress concentrations at the fault tips and the effects of fault length. In this model, induced stress analysis in a full-space under the plane strain condition is implemented based on Eshelby's theory of inclusions in terms of a homogeneous, isotropic, and poroelastic medium. The stress intensity factor concept in linear elastic fracture mechanics is adopted as an instability criterion for pre-existing faults in surrounding rocks. To characterize the fault reactivation caused by fluid injection and extraction, we define a new index, the "fault reactivation factor" η, which can be interpreted as an index of fault stability in response to fluid pressure changes per unit within a reservoir resulting from injection or extraction. The critical fluid pressure change within a reservoir is also determined by the superposition principle using the in situ stress surrounding a fault. Our parameter sensitivity analyses show that the fault reactivation tendency is strongly sensitive to fault location, fault length, fault dip angle, and Poisson's ratio of the surrounding rock. Our case study demonstrates that the proposed model focuses on the mechanical behavior of the whole fault, unlike the conventional methodologies. The proposed method can be applied to engineering cases related to injection and depletion within a reservoir owing to its efficient computational codes implementation.

  5. Immunogenicity and Safety of Trivalent Split Influenza Vaccine in Healthy Korean Adults with Low Pre-Existing Antibody Levels: An Open Phase I Trial

    PubMed Central

    Kang, Kyuri; Han, Seunghoon; Hong, Taegon; Jeon, Sangil; Paek, Jeongki; Kang, Jin Han

    2016-01-01

    Purpose A phase I clinical trial was conducted to evaluate the immunogenicity and safety of newly developed egg-cultivated trivalent inactivated split influenza vaccine (TIV) in Korea. Materials and Methods The TIV was administered to 43 healthy male adults. Subjects with high pre-existing titers were excluded in a screening step. Immune response was measured by a hemagglutination inhibition (HI) assay. Results The seroprotection rates against A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2009 were 74.42% [95% confidence interval (CI): 61.38–87.46], 72.09% (95% CI: 58.69–85.50), and 86.05% (95% CI: 75.69–96.40), respectively. Calculated seroconversion rates were 74.42% (95% CI: 61.38–87.46), 74.42% (95% CI: 61.38–87.46), and 79.07% (95% CI: 66.91–91.23), respectively. There were 25 episodes of solicited local adverse events in 21 subjects (47.73%), 21 episodes of solicited general adverse events in 16 subjects (36.36%) and 5 episodes of unsolicited adverse events in 5 subjects (11.36%). All adverse events were grade 1 or 2 and disappeared within three days. Conclusion The immunogenicity and safety of TIV established in this phase I trial are sufficient to plan a larger scale clinical trial. PMID:27593862

  6. Mortality patterns associated with the 1918 influenza pandemic in Mexico: evidence for a spring herald wave and lack of pre-existing immunity in older populations

    PubMed Central

    Chowell, Gerardo; Viboud, Cécile; Simonsen, Lone; Miller, Mark A.; Acuna-Soto, Rodolfo

    2010-01-01

    Background While the mortality burden of the devastating 1918 influenza pandemic has been carefully quantified in the US, Japan, and European countries, little is known about the pandemic experience elsewhere. Here, we compiled extensive archival records to quantify the pandemic mortality patterns in two Mexican cities, Mexico City and Toluca. Methods We applied seasonal excess mortality models to age-specific respiratory mortality rates for 1915–1920 and quantified the reproduction number from daily data. Results We identified 3 pandemic waves in Mexico City in spring 1918, fall 1918, and winter 1920, characterized by unusual excess mortality in 25–44 years old. Toluca experienced 2-fold higher excess mortality rates than Mexico City, but did not have a substantial 3rd wave. All age groups including those over 65 years experienced excess mortality during 1918–20. Reproduction number estimates were below 2.5 assuming a 3-day generation interval. Conclusion Mexico experienced a herald pandemic wave with elevated young adult mortality in spring 1918, similar to the US and Europe. In contrast to the US and Europe, there was no mortality sparing in Mexican seniors, highlighting potential geographical differences in pre-existing immunity to the 1918 virus. We discuss the relevance of our findings to the 2009 pandemic mortality patterns. PMID:20594109

  7. Pre-existence and Persistence of Resistant Minority Hepatitis C Virus Variants in Genotype 1-Infected Patients Treated With Simeprevir/Peginterferon/Ribavirin.

    PubMed

    Fevery, Bart; Thys, Kim; Van Eygen, Veerle; Verbinnen, Thierry; Van Rossem, Elizabeth; Buelens, Annemie; Aerssens, Jeroen; Witek, James; Picchio, Gaston; De Meyer, Sandra; Lenz, Oliver

    2016-03-01

    Background.  The pre-existence of minority hepatitis C virus (HCV) variants and their impact on treatment outcome, as well as the persistence of emerging resistant variants posttreatment in patients failing treatment with simeprevir/peginterferon/ribavirin (SMV/PR), were assessed by deep sequencing (DS). Methods.  Population sequencing (PS) and Illumina DS were performed on HCV genotype 1 isolates from patients treated with SMV/PR in Phase 2b (PILLAR [NCT00882908] and ASPIRE [NCT00980330]) and Phase 3 (QUEST-1 [NCT01289782], QUEST-2 [NCT01290679], and PROMISE [NCT01281839]) trials. Results.  Minority polymorphisms (ie, detected pretreatment by DS only) reducing SMV activity in vitro were uncommon (3.6%, 19 of 534 patients). These SMV-resistant minority polymorphisms were detected in similar proportions of patients achieving (3.7%) and not achieving (3.3%) sustained virologic response with SMV/PR and generally did not emerge as major variants at time of failure. SMV-resistant variants emerging at time of failure were no longer detected at end of study in 69.3% and 52.0% of the patients by PS and DS, respectively. Conclusions.  Minority polymorphisms did not impact outcome of SMV/PR treatment. The majority of emerging variants that became undetectable at end of study by PS were also undetectable by DS. These results suggest no added value of DS for clinical usage of SMV.

  8. A Critical Shock Mach Number for Particle Acceleration in the Absence of Pre-existing Cosmic Rays: M=\\sqrt{5}

    NASA Astrophysics Data System (ADS)

    Vink, Jacco; Yamazaki, Ryo

    2014-01-01

    It is shown that, under some generic assumptions, shocks cannot accelerate particles unless the overall shock Mach number exceeds a critical value M\\gt\\sqrt{5}. The reason is that for M\\le \\sqrt{5} the work done to compress the flow in a particle precursor requires more enthalpy flux than the system can sustain. This lower limit applies to situations without significant magnetic field pressure. In case that the magnetic field pressure dominates the pressure in the unshocked medium, i.e., for low plasma beta, the resistivity of the magnetic field makes it even more difficult to fulfill the energetic requirements for the formation of shock with an accelerated particle precursor and associated compression of the upstream plasma. We illustrate the effects of magnetic fields for the extreme situation of a purely perpendicular magnetic field configuration with plasma beta β = 0, which gives a minimum Mach number of M = 5/2. The situation becomes more complex, if we incorporate the effects of pre-existing cosmic rays, indicating that the additional degree of freedom allows for less strict Mach number limits on acceleration. We discuss the implications of this result for low Mach number shock acceleration as found in solar system shocks, and shocks in clusters of galaxies.

  9. The effects of aerobic- versus strength-training on body image among young women with pre-existing body image concerns.

    PubMed

    Martin Ginis, Kathleen A; Strong, Heather A; Arent, Shawn M; Bray, Steven R; Bassett-Gunter, Rebecca L

    2014-06-01

    This experiment compared the effects of aerobic-training (AT) versus strength-training (ST) on body image among young women with pre-existing body image concerns. Theory-based correlates of body image change were also examined. Participants were 46 women (M age=21.5 years), randomly assigned to an 8-week AT or ST intervention consisting of supervised exercise 3 days/week. Multidimensional measures of body image were administered pre- and post-intervention, along with measures of physical fitness, perceived fitness, and exercise self-efficacy. Women in the AT condition reported greater reductions in social physique anxiety (p=.001) and tended to report greater improvements in appearance evaluation (p=.06) than women in the ST condition. Changes in perceived fatness, perceived aerobic endurance and aerobic self-efficacy were significantly correlated with body image change (ps<.003). Results provide direction for prescribing exercise to improve body image and advancing theory to account for the effects of exercise.

  10. Pre-existing cross-reactive antibodies to avian influenza H5N1 and 2009 pandemic H1N1 in US military personnel.

    PubMed

    Pichyangkul, Sathit; Krasaesub, Somporn; Jongkaewwattana, Anan; Thitithanyanont, Arunee; Wiboon-Ut, Suwimon; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Mongkolsirichaikul, Duangrat; Khemnu, Nuanpan; Mahanonda, Rangsini; Garcia, Jean-Michel; Mason, Carl J; Walsh, Douglas S; Saunders, David L

    2014-01-01

    We studied cross-reactive antibodies against avian influenza H5N1 and 2009 pandemic (p) H1N1 in 200 serum samples from US military personnel collected before the H1N1 pandemic. Assays used to measure antibodies against viral proteins involved in protection included a hemagglutination inhibition (HI) assay and a neuraminidase inhibition (NI) assay. Viral neutralization by antibodies against avian influenza H5N1 and 2009 pH1N1 was assessed by influenza (H5) pseudotyped lentiviral particle-based and H1N1 microneutralization assays. Some US military personnel had cross-neutralizing antibodies against H5N1 (14%) and 2009 pH1N1 (16.5%). The odds of having cross-neutralizing antibodies against 2009 pH1N1 were 4.4 times higher in subjects receiving more than five inactivated whole influenza virus vaccinations than those subjects with no record of vaccination. Although unclear if the result of prior vaccination or disease exposure, these pre-existing antibodies may prevent or reduce disease severity.

  11. Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3

    PubMed Central

    Maekawa, Tomoki; Briones, Ruel A.; Resuello, Ranillo R.G.; Tuplano, Joel V.; Hajishengallis, Evlambia; Kajikawa, Tetsuhiro; Koutsogiannaki, Sophia; Garcia, Cristina A.G.; Ricklin, Daniel; Lambris, John D.; Hajishengallis, George

    2016-01-01

    Aim Human periodontitis is associated with overactivation of complement, which is triggered by different mechanisms converging on C3, the central hub of the system. We assessed whether the C3 inhibitor Cp40 inhibits naturally-occurring periodontitis in non-human primates. Materials and Methods Non-human primates with chronic periodontitis were intra-gingivally injected with Cp40 either once (5 animals) or three times (10 animals) weekly for six weeks followed by a 6-week follow-up period. Clinical periodontal examinations and collection of gingival crevicular fluid and biopsies of gingiva and bone were performed at baseline and during the study. A one-way repeated measures ANOVA was used for data analysis. Results Whether administered once or three times weekly, Cp40 caused a significant reduction in clinical indices that measure periodontal inflammation (gingival index and bleeding on probing), tissue destruction (probing pocket depth and clinical attachment level) or tooth mobility. These clinical changes were associated with significantly reduced levels of pro-inflammatory mediators and decreased numbers of osteoclasts in bone biopsies. The protective effects of Cp40 persisted, albeit at reduced efficacy, for at least six weeks following drug discontinuation. Conclusion Cp40 inhibits pre-existing chronic periodontal inflammation and osteoclastogenesis in non-human primates, suggesting a novel adjunctive anti-inflammatory therapy for treating human periodontitis. PMID:26728318

  12. Lack of variant specific CD8+ T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C

    PubMed Central

    2013-01-01

    Background CTL escape mutations have been described during acute hepatitis C in patients who developed chronic disease later on. Our aim was to investigate the mutual relationship between HCV specific CD8+ T cells and evolution of the viral sequence during early acute HCV infection. Results We sequenced multiple clones of NS3 1406 epitope in 4 HLA-A*02 patients with acute hepatitis C genotype 1b infection. Pentamers specific for the variants were used to monitor the corresponding CD8+ T cell response. We observed outgrowth of mutations, which induced only a weak and thus potentially insufficient CD8+ T cell response. In one patient we observed outgrowth of variant epitopes with similarities to a different genotype rather than de novo mutations most probably due to a lack of responsiveness to these likely pre-existing variants. We could show that in acute hepatitis C CTL escape mutations occur much earlier than demonstrated in previous studies. Conclusions The adaption of the virus to a new host is characterized by a high and rapid variability in epitopes under CD8+ T cell immune pressure. This adaption takes place during the very early phase of acute infection and strikingly some sequences were reduced below the limit of detection at some time points but were detected at high frequency again at later time points. Independent of the observed variability, HCV-specific CD8+ T cell responses decline and no adaption to different or new antigens during the course of infection could be detected. PMID:24073713

  13. Effects of blending of desalinated and conventionally treated surface water on iron corrosion and its release from corroding surfaces and pre-existing scales.

    PubMed

    Liu, Haizhou; Schonberger, Kenneth D; Peng, Ching-Yu; Ferguson, John F; Desormeaux, Erik; Meyerhofer, Paul; Luckenbach, Heidi; Korshin, Gregory V

    2013-07-01

    This study examined effects of blending desalinated water with conventionally treated surface water on iron corrosion and release from corroding metal surfaces and pre-existing scales exposed to waters having varying fractions of desalinated water, alkalinities, pH values and orthophosphate levels. The presence of desalinated water resulted in markedly decreased 0.45 μm-filtered soluble iron concentrations. However, higher fractions of desalinated water in the blends were also associated with more fragile corroding surfaces, lower retention of iron oxidation products and release of larger iron particles in the bulk water. SEM, XRD and XANES data showed that in surface water, a dense layer of amorphous ferrihydrite phase predominated in the corrosion products. More crystalline surface phases developed in the presence of desalinated water. These solid phases transformed from goethite to lepidocrocite with increased fraction of desalinated water. These effects are likely to result from a combination of chemical parameters, notably variations of the concentrations of natural organic matter, calcium, chloride and sulfate when desalinated and conventionally treated waters are blended.

  14. Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves' disease.

    PubMed

    Zhu, Cheng-Yao; Zhang, Guo-Xue; Yu, Zuo-Zhong; Li, Zhao-Jun; Fan, Yi-Ming

    2014-04-01

    A 35-year-old woman with postoperative recurrent Graves' disease presented with a 5-day history of a red swelling on the right cheek associated with 4 days of remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her white blood cell count, immunoglobulins, and lymphocyte subsets were unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated erythematous plaque occurred on the right leg on hospital day 3. She was treated with intravenous antibiotics with topical gentamicin, recombinant bovine basic fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The ulcer healed leaving a depressed scar at 35 days after discharge. This patient may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis in postoperative recurrent Graves' disease.

  15. Ecthyma gangrenosum, a skin manifestation of Pseudomonas aeruginosa sepsis in a previously healthy child

    PubMed Central

    Biscaye, Stephanie; Demonchy, Diane; Afanetti, Mickael; Dupont, Audrey; Haas, Herve; Tran, Antoine

    2017-01-01

    Abstract Rationale: Ecthyma gangrenosum (Eg) is a necrotic lesion that is mostly seen in immunocompromised patients. It reflects a severe sepsis, possibly caused by Pseudomonas aeruginosa (Pa). Patient concerns: A healthy 3-year-old girl admitted to the Pediatric Emergency Department presented a sepsis-associated purpura with neurological and respiratory distress. Interventions: An empiric antibiotherapy (anti-meningococcal) was prescribed. Diagnoses: Forty-eight hours after admission, blood and wound cultures were positive for Pa. As a result, the decision was made to change the antibiotic therapy. Unfortunately, on day 3, the patient died. Exhaustive immunologic tests are presently being carried out. Outcomes: Eg caused by Pa is uncommon in healthy children, and purpura sepsis is usually caused by Neisseria meningitides infection. Lessons: Eg should be recognized rapidly so that the appropriate treatment can be prescribed as quickly as possible. PMID:28079790

  16. The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis

    PubMed Central

    Zhang, Bin; Liang, Long; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

    2015-01-01

    Objective The aim of this meta-analysis was to explore the efficacy of sodium bicarbonate in preventing contrast-induced nephropathy (CIN). Methods We searched PubMed, Medline and the Cochrane Library from 1 January 2004 to 1 August 2014. The effect estimate was expressed as a pooled OR with 95% CI, using the fixed-effects or random-effects model. Results 20 randomised controlled trials (n=4280) were identified. Hydration with sodium bicarbonate was associated with a significant decrease in CIN among patients with pre-existing renal insufficiency (OR 0.67, 95% CI 0.47 to 0.96; p=0.027). However, moderate heterogeneity was noted across trials (I2=48%; p=0.008). Subgroup analyses indicated a better effect of sodium bicarbonate in studies using low-osmolar (OR 0.59, 95% CI 0.37 to 0.93; p=0.024) compared with iso-osmolar contrast agents (OR 0.76, 95% CI 0.43 to 1.34; p=0.351). The odds of CIN with sodium bicarbonate were lower in studies including only patients undergoing emergency (OR 0.16, 95% CI 0.05 to 0.51; p=0.002) compared with elective procedures (OR 0.76, 95% CI 0.54 to 1.06; p=0.105). Sodium bicarbonate was more beneficial in patients given a bolus injection before procedures (OR 0.15, 95% CI 0.04 to 0.54; p=0.004) compared with continuous infusion (OR 0.75, 95% CI 0.53 to 1.05; p=0.091). Sodium bicarbonate plus N-acetylcysteine (OR 0.17, 95% CI 0.04 to 0.79; p=0.024) was better than sodium bicarbonate alone (OR 0.71, 95% CI 0.48 to 1.03; p=0.071). The effect of sodium bicarbonate was considered greater in papers published before (OR 0.19, 95% CI 0.09 to 0.41; p=0.000) compared with after 2008 (OR 0.85, 95% CI 0.62 to 1.16; p=0.302). However, no significant differences were found in mortality (OR 0.69, 95% CI 0.36 to 1.32; p=0.263) or requirement for dialysis (OR 1.08, 95% CI 0.52 to 2.25; p=0.841). Conclusions Sodium bicarbonate is effective in preventing CIN among patients with pre-existing renal insufficiency. However, it fails to lower the risks of

  17. Modeling Aseismic and Seismic Slip Induced by Fluid Injection on Pre-existing Faults Governed by Rate-and-state Friction

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Harrington, R. M.; Deng, K.; Larochelle, S.

    2015-12-01

    Pore fluid pressure evolution on pre-existing faults in the vicinity of fluid injection activity has been postulated as a key factor for inducing both moderate size earthquakes and aseismic slip. In this study, we develop a numerical model incorporating rate-and-state friction properties to investigate fault slip initiated by various perturbations, including fluid injection and transient dynamic stress changes. In the framework of rate-and-state friction, external stress perturbations and their spatiotemporal variation can be coupled to fault frictional strength evolution in a single computational procedure. Hence it provides a quantitative understanding of the source processes (i.e., slip rate, rupture area, triggering threshold) of a spectrum of slip modes under the influence of anthropogenic and natural perturbations. Preliminary results show both the peak and cumulative Coulomb stress change values can affect the transition from aseismic to seismic slip and the amount of slip. We plan to apply the physics-based slip model to induced earthquakes in western Canada sedimentary basins. In particular, we will focus on the Fox Creek sequences in north Alberta, where two earthquakes of ML4.4 (2015/01/23) and Mw4.6 (2015/06/13) were potentially induced by nearby hydraulic fracturing activity. The geometry of the seismogenic faults of the two events will be constrained by relocated seismicity as well as their focal mechanism solutions. Rate-and-state friction parameters and ambient stress conditions will be constrained by identifying dynamic triggering criteria using a matched-filter approach. A poroelastic model will be used to estimate the pore pressure history resolved onto the fault plane due to fluid injection. By comparing modeled earthquake source parameters to those estimated from seismic analysis, we aim to quantitatively discern the nucleation conditions of injection-induced versus dynamically triggered earthquakes, and aseismic versus seismic slip modes.

  18. Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques

    PubMed Central

    Jaworski, Juan Pablo; Bryk, Peter; Brower, Zachary; Zheng, Bo; Hessell, Ann J.; Rosenberg, Alexander F.; Wu, Tong Tong; Sanz, Ignacio; Keefer, Michael C.; Haigwood, Nancy L.

    2017-01-01

    Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig) purified from previously infected animals (SHIVIG) or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2–3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host’s ability to eliminate HIV. PMID:28222180

  19. The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry.

    PubMed

    Oliva, Karen; Barker, Gillian; Riley, Clyde; Bailey, Mark J; Permezel, Michael; Rice, Gregory E; Lappas, Martha

    2012-04-01

    Our aim was to study the protein expression profiles of placenta obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section. We used two-dimensional difference gel electrophoresis (2D-DIGE), utilising narrow-range immobilised pH gradient strips that encompassed the broad pH range of 4-5 and 5-6, followed by MALDI-TOF mass spectrometry of selected protein spots. Western blot and quantitative RT-PCR (qRT-PCR) analyses were performed to validate representative findings from the 2D-DIGE analysis. Eight proteins were altered (six down-regulated and two up-regulated on obese placentas). Annexin A5 (ANXA5), ATP synthase subunit beta, mitochondria (ATPB), brain acid soluble protein 1 (BASP1), ferritin light chain (FTL), heterogeneous nuclear ribonucleoprotein C (HNRPC) and vimentin (VIME) were all lower in obese patients. Alpha-1-antitrypsin (A1AT) and stress-70 protein, mitochondrial (GRP75) were higher in obese patients. Western blot analysis of ANXA5, ATPB, FTL, VIME, A1AT and GRP75 confirmed the findings from the 2D-DIGE analysis. For brain acid soluble protein 1 and HNRPC, qRT-PCR analysis also confirmed the findings from the 2D-DIGE analysis. Immunohistochemical analysis was also used to determine the localisation of the proteins in human placenta. In conclusion, proteomic analysis of placenta reveals differential expression of several proteins in patients with pre-existing obesity. These proteins are implicated in a variety of cellular functions such as regulation of growth, cytoskeletal structure, oxidative stress, inflammation, coagulation and apoptosis. These disturbances may have significant implications for fetal growth and development.

  20. α-Synuclein Oligomers Stabilize Pre-Existing Defects in Supported Bilayers and Propagate Membrane Damage in a Fractal-Like Pattern.

    PubMed

    Chaudhary, Himanshu; Iyer, Aditya; Subramaniam, Vinod; Claessens, Mireille M A E

    2016-11-15

    Phospholipid vesicles are commonly used to get insights into the mechanism by which oligomers of amyloidogenic proteins damage membranes. Oligomers of the protein α-synuclein (αS) are thought to create pores in phospholipid vesicles containing a high amount of anionic phospholipids but fail to damage vesicle membranes at low surface charge densities. The current understanding of how αS oligomers damage the membranes is thus incomplete. This incomplete understanding may, in part, result from the choice of model membrane systems. The use of free-standing membranes such as vesicles may interfere with the unraveling of some damage mechanisms because the line tension at the edge of a membrane defect or pore ensures defect closure. Here, we have used supported lipid bilayers (SLBs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPC/POPS) to study the membrane damage caused by αS oligomers. Although αS oligomers were not able to initiate the disruption of POPC/POPS vesicles or intact SLBs, oligomers did stabilize and enlarge pre-existing SLB defects. The increased exposure of lipid acyl chains at the edges of defects very likely facilitates membrane-oligomer interactions, resulting in the growth of fractal domains devoid of lipids. Concomitant with the appearance of the fractal membrane damage patterns, lipids appear in solution, directly implicating αS oligomers in the observed lipid extraction. The growth of the membrane damage patterns is not limited by the binding of lipids to the oligomer. The analysis of the shape and growth of the lipid-free domains suggests the involvement of an oligomer-dependent diffusion-limited extraction mechanism. The observed αS oligomer-induced propagation of membrane defects offers new insights into the mechanisms by which αS oligomers can contribute to the loss in membrane integrity.

  1. A Rapid-Response Humoral Vaccine Platform Exploiting Pre-Existing Non-Cognate Populations of Anti-Vaccine or Anti-Viral CD4+ T Helper Cells to Confirm B Cell Activation

    PubMed Central

    Hills, Thomas; Jakeman, Phillip G.; Carlisle, Robert C.; Klenerman, Paul; Seymour, Leonard W.; Cawood, Ryan

    2016-01-01

    The need for CD4+ T cell responses to arise de novo following vaccination can limit the speed of B cell responses. Populations of pre-existing vaccine-induced or anti-viral CD4+ T cells recognising distinct antigens could be exploited to overcome this limitation. We hypothesise that liposomal vaccine particles encapsulating epitopes that are recognised, after processing and B cell MHCII presentation, by pre-existing CD4+ T cells will exploit this pre-existing T cell help and result in improved antibody responses to distinct target antigens displayed on the particle surface. Liposomal vaccine particles were engineered to display the malaria circumsporozoite (CSP) antigen on their surface, with helper CD4+ epitopes from distinct vaccine or viral antigens contained within the particle core, ensuring the B cell response is raised but focused against CSP. In vivo vaccination studies were then conducted in C57Bl/6 mice as models of either vaccine-induced pre-existing CD4+ T cell immunity (using ovalbumin—OVA) or virus-induced pre-existing CD4+ T cell immunity (murine cytomegalovirus—MCMV). Following the establishment of pre-existing by vaccination (OVA in the adjuvant TiterMax® Gold) or infection with MCMV, mice were administered CSP-coated liposomal vaccines containing the relevant OVA or MCMV core CD4+ T cell epitopes. In mice with pre-existing anti-OVA CD4+ T cell immunity, these vaccine particles elicited rapid, high-titre, isotype-switched CSP-specific antibody responses—consistent with the involvement of anti-OVA T helper cells in confirming activation of anti-CSP B cells. Responses were further improved by entrapping TLR9 agonists, combining humoral vaccination signals ‘one’, ‘two’ and ‘three’ within one particle. Herpes viruses can establish chronic infection and elicit significant, persistent cellular immune responses. We then demonstrate that this principle can be extended to re-purpose pre-existing anti-MCMV immunity to enhance anti

  2. Modeling fault kinematics, segment interaction and transfer zone geometry as a function of pre-existing fabrics: the Albertine rift, East African Rift System.

    NASA Astrophysics Data System (ADS)

    Aanyu, Kevin; Koehn, Daniel

    2010-05-01

    This study focuses on the development of the Rwenzori Mountains, an uplift horst block within the northern-most segment of the western branch of the East African Rift System (EARS). Attention is drawn to the role of pre-existing crustal weaknesses left behind by Proterozoic mobile belts that pass around cratonic Archean shields namely the Tanzanian Craton to the southeast and the Congo craton to the northwest. We study how the southward propagating sub-segment of the rift that contains Lake Albert to the north interacts with the northward propagating sub-segment that contains the lakes Edward and George and how this interaction produces the structural geometries observed within and around the Rwenzori horst block. Analogue experiments are used to simulate behavior of the upper crust with pre-cut rubber strips of varying overstep/overlap, placed oblique and/or orthogonal to the extension vector. The points of connection to the basal sheet present velocity discontinuities to localize deformation below the sand. Surface geometry of the developing rifts and section cuts are used to study the kinematics that result from the given boundary conditions. In general we try to model two parallel rifts that propagate towards each other and interact. Results show that greater overstep of rifts produces an oblique shear-dominated transfer zone with deep grabens (max.7.0km) in the adjoining segments. Smaller overlap ends in extension-dominated transfer, offset rift segments without oblique transfer faults to join two adjacent rift arms and produces moderately deep grabens (max.4.6km). When overlap doubles the overstep (SbR5), rifts propagate sub-orthogonal to the extension direction in a rotation-dominated transfer and form shallow valleys (max.2.9km). Whether a block like the Rwenzori Mountains is captured and rotates, depends on the overlap/overstep ratio where the rotation direction of a captured block is determined by the sense of overlap (right- or left-lateral). Fault

  3. Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients

    PubMed Central

    Zhang, Yu; Cao, Ying; Zhang, Renwen; Zhang, Xiaxia; Lu, Haiying; Wu, Chihong; Huo, Na; Xu, Xiaoyuan

    2016-01-01

    Background The efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline. Methods Direct sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus. Results The incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region. Conclusions Pre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline. PMID:27812165

  4. Pre-existing type 2 diabetes mellitus is an independent risk factor for mortality and progression in patients with renal cell carcinoma.

    PubMed

    Vavallo, Antonio; Simone, Simona; Lucarelli, Giuseppe; Rutigliano, Monica; Galleggiante, Vanessa; Grandaliano, Giuseppe; Gesualdo, Loreto; Campagna, Marcello; Cariello, Marica; Ranieri, Elena; Pertosa, Giovanni; Lastilla, Gaetano; Selvaggi, Francesco Paolo; Ditonno, Pasquale; Battaglia, Michele

    2014-12-01

    Malignancies are one of the main causes of mortality in diabetic patients; however, to date, very limited data have been reported on the specific influence of type 2 diabetes mellitus (T2DM) on the survival of patients with renal cell carcinoma (RCC). In the present long-term retrospective study, we investigated whether T2DM may influence the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with surgically treated RCC. Medical records of 924 patients treated by radical or partial nephrectomy for sporadic, unilateral RCC were reviewed. Patients with type-1 DM and with T2 DM receiving insulin treatment were excluded. Survival estimates were calculated according to the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were performed using the Cox regression model.Of the 924 RCC patients, 152 (16.5%) had T2DM. Mean follow-up was 68.5 months. Mean OS was 41.3 and 96.3 months in T2DM and non-T2DM patients, respectively (P < 0.0001).The estimated CSS rates at 1, 3, and 5 years in T2DM versus non-T2DM patients were 63.4% versus 76.7%, 30.4% versus 56.6%, and 16.3% versus 48.6%, respectively (P = 0.001). Mean PFS was significantly lower (31.5 vs 96.3 months; P < 0.0001) in the T2DM group. At multivariate analysis, T2DM was an independent adverse prognostic factor for OS (hazard ratio [HR]  = 3.44; 95% confidence interval [CI]:2.40-4.92), CSS (HR = 6.39; 95% CI: 3.78-10.79), and PFS (HR = 4.71; 95% CI: 3.11-7.15). In conclusion, our findings suggest that patients with RCC and pre-existing T2DM have a shorter OS, increased risk of recurrence, and higher risk for kidney cancer mortality than those without diabetes.

  5. Photosynthetic traits around budbreak in pre-existing needles of Sakhalin spruce (Picea glehnii) seedlings grown under elevated CO2 concentration assessed by chlorophyll fluorescence measurements.

    PubMed

    Kitao, Mitsutoshi; Tobita, Hiroyuki; Utsugi, Hajime; Komatsu, Masabumi; Kitaoka, Satoshi; Maruyama, Yutaka; Koike, Takayoshi

    2012-08-01

    To assess the effects of elevated CO(2) concentration ([CO(2)]) on the photosynthetic properties around spring budbreak, we monitored the total leaf sugar and starch content, and chlorophyll fluorescence in 1-year-old needles of Sakhalin spruce (Picea glehnii Masters) seedlings in relation to the timing of budbreak, grown in a phytotron under natural daylight at two [CO(2)] levels (ambient: 360 μmol mol(-1) and elevated: 720 μmol mol(-1)). Budbreak was accelerated by elevated [CO(2)] accompanied with earlier temporal declines in the quantum yield of PSII electron transport (Φ(PSII)) and photochemical quenching (q(L)). Plants grown under elevated [CO(2)] showed pre-budbreak leaf starch content twice as high with no significant difference in Φ(PSII) from ambient-CO(2)-grown plants when compared at the same measurement [CO(2)], i.e., 360 or 720 μmol mol(-1), suggesting that the enhanced pre-budbreak leaf starch accumulation might not cause down-regulation of photosynthesis in pre-existing needles under elevated [CO(2)]. Conversely, lower excitation pressure adjusted for the efficiency of PSII photochemistry ((1 - q(P)) F(v)'/F(m)') was observed in plants grown under elevated [CO(2)] around budbreak when compared at their growth [CO(2)] (i.e., comparing (1 - q(P)) F(v)'/F(m)' measured at 720 μmol mol(-1) in elevated-CO(2)-grown plants with that at 360 μmol mol(-1) in ambient-CO(2)-grown plants), which suggests lower rate of photoinactivation of PSII in the elevated-CO(2)-grown plants around spring budbreak. The degree of photoinhibition, as indicated by the overnight-dark-adapted F(v)/F(m), however, showed no difference between CO(2) treatments, thereby suggesting that photoprotection during the daytime or the repair of PSII at night was sufficient to alleviate differences in the rate of photoinactivation.

  6. Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study.

    PubMed

    Bell, R; Glinianaia, S V; Tennant, P W G; Bilous, R W; Rankin, J

    2012-02-08

    AIMS: The aim of this study was to quantify the risk of major congenital anomaly, and to assess the influence of peri-conception HbA(1c) and other clinical and socio-demographic factors on the risk of congenital anomaly occurrence in offspring of women with type 1 and type 2 diabetes diagnosed before pregnancy. METHODS: This was a population-based cohort study using linked data from registers of congenital anomaly and diabetes in pregnancy. A total of 401,149 singleton pregnancies (1,677 in women with diabetes) between 1996 and 2008 resulting in live birth, fetal death at ≥20 weeks' gestation or termination of pregnancy for fetal anomaly were included. RESULTS: The rate of non-chromosomal major congenital anomaly in women with diabetes was 71.6 per 1,000 pregnancies (95% CI 59.6, 84.9), a relative risk of 3.8 (95% CI 3.2, 4.5) compared with women without diabetes. There was a three- to sixfold increased risk across all common anomaly groups. In a multivariate analysis, peri-conception glycaemic control (adjusted OR [aOR] 1.3 [95% CI 1.2, 1.4] per 1% [11 mmol/mol] linear increase in HbA(1c) above 6.3% [45 mmol/mol]) and pre-existing nephropathy (aOR 2.5 [95% CI 1.1, 5.3]) were significant independent predictors of congenital anomaly. Associations with gestation at booking (aOR 1.1 [95% CI 1.0, 1.1]) and parity (aOR 1.6 [95% CI 1.0, 2. 5]) were not significant. Unadjusted risk was higher for women from deprived areas or who did not take folate. Type and duration of diabetes, ethnicity, age, BMI, preconception care, smoking and fetal sex were not associated with congenital anomaly risk. CONCLUSIONS: Peri-conception glycaemia is the most important modifiable risk factor for congenital anomaly in women with diabetes. The association with nephropathy merits further study.

  7. Testing the influence of vertical, pre-existing joints on normal faulting using analogue and 3D discrete element models (DEM)

    NASA Astrophysics Data System (ADS)

    Kettermann, Michael; von Hagke, Christoph; Virgo, Simon; Urai, Janos L.

    2015-04-01

    Brittle rocks are often affected by different generations of fractures that influence each other. We study pre-existing vertical joints followed by a faulting event. Understanding the effect of these interactions on fracture/fault geometries as well as the development of dilatancy and the formation of cavities as potential fluid pathways is crucial for reservoir quality prediction and production. Our approach combines scaled analogue and numerical modeling. Using cohesive hemihydrate powder allows us to create open fractures prior to faulting. The physical models are reproduced using the ESyS-Particle discrete element Modeling Software (DEM), and different parameters are investigated. Analogue models were carried out in a manually driven deformation box (30x28x20 cm) with a 60° dipping pre-defined basement fault and 4.5 cm of displacement. To produce open joints prior to faulting, sheets of paper were mounted in the box to a depth of 5 cm at a spacing of 2.5 cm. Powder was then sieved into the box, embedding the paper almost entirely (column height of 19 cm), and the paper was removed. We tested the influence of different angles between the strike of the basement fault and the joint set (0°, 4°, 8°, 12°, 16°, 20°, and 25°). During deformation we captured structural information by time-lapse photography that allows particle imaging velocimetry analyses (PIV) to detect localized deformation at every increment of displacement. Post-mortem photogrammetry preserves the final 3-dimensional structure of the fault zone. We observe that no faults or fractures occur parallel to basement-fault strike. Secondary fractures are mostly oriented normal to primary joints. At the final stage of the experiments we analyzed semi-quantitatively the number of connected joints, number of secondary fractures, degree of segmentation (i.e. number of joints accommodating strain), damage zone width, and the map-view area fraction of open gaps. Whereas the area fraction does not change

  8. Risk factors associated with the antimicrobial resistance of staphylococci in canine pyoderma.

    PubMed

    Huerta, Belén; Maldonado, Alfonso; Ginel, Pedro J; Tarradas, Carmen; Gómez-Gascón, Lidia; Astorga, Rafael J; Luque, Inmaculada

    2011-06-02

    This study reports the susceptibility to antimicrobial agents of staphylococci (n=105) isolated from dogs, and the factors associated with this resistance. The study animals were 23 healthy dogs (group A), 24 with first-time pyoderma (group B), and 27 with recurrent pyoderma that had undergone long-term antibiotic treatment (group C). Staphylococci were more commonly isolated from the pyoderma-affected than the healthy dogs (p<0.0001). Some 78% of the isolates were resistant to at least one antimicrobial agent. Resistance to amoxicillin-clavulanate, cephalosporins (OR 4.29, 95% CI [1.15, 16.3] respectively), enrofloxacin (OR 9.47, 95% CI [1.53, 58.5]) and ciprofloxacin (OR 79.7 95% CI [3.26, 1947.4]) was more common among group C isolates. Some 32% of all the isolates were multiresistant (MR) and 10.4% were methicillin-resistant (MRS). The probability of isolating MRS staphylococci in group C increased by a factor of four (95% CI [1.18, 17.9]) compared to A plus B. Multi-resistant (MR) isolates were obtained more commonly from urban than rural dogs (OR 3.79, 95% CI [1.09, 13.17]). All the MRS staphylococci encountered were obtained from urban dogs and more commonly from male dogs (p=0.07). This study shows that dogs bred in urban habitat, with a history of antibiotic therapy in the past year represents significant risk of being carriers of isolates resistant to methicillin (MRS) and other antimicrobials. These factors should be considered before applying an antimicrobial treatment in veterinary clinics.

  9. Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections.

    PubMed

    Guidry, Jacqueline A; Downing, Christopher; Tyring, Stephen K

    2015-07-01

    Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline.

  10. Origin of the Ciomadul Dacite, Carpathian-Pannonian Region, Eastern-Central Europe: Rejuvenation of a Pre-Existing Crystal Mush

    NASA Astrophysics Data System (ADS)

    Kiss, B.; Harangi, S.; Molnar, K.; Jankovics, E. M.; Lukacs, R.; Ntaflos, T.

    2012-12-01

    Dacitic composite volcanoes and calderas worldwide have many common specific characters. Notably, their activities are fairly unpredictable since the repose time between the active phases could be rather long, i.e. even several tens or hundreds ka. This nature might be related to the origin of such magmas. Petrological observations indicate that relatively old, cool, highly crystalline magma body (i.e., a crystal mush) could be present beneath the seemingly inactive dacitic volcanoes before reawakening. Reactivation of such locked magma chambers could occur due to the upwelling and intrusion of mafic magma and recent calculations suggest that this process takes place rather fast. Understanding the nature and time-scale of such remobilization events is crucial to explain the reason of the change in volcanic behaviour from dormant to active phase (i.e., the reawakening of the volcano). In this study, we show the role and the character of a pre-existing near-solidus granodioritic crystal mush to generate the eruptible dacitic magma in the Ciomadul volcano. The Ciomadul dacite is a crystal-rich rock with ubiquitous plagioclases and amphiboles. They form viscous lava domes and pumices generated by sub-plinian explosive eruptions. Combined, mineral-scale textural and geochemical investigations indicate a complex origin of these minerals, formed partly in a low temperature dioritic-granodioritic crystal mush body, partly in higher temperature hybrid magma. In addition, biotite, titanite, apatite, allanite, zircon, K-feldspar and quartz occur in various amounts and are interpreted also as antecrysts derived from the remobilized mushy body. High-Mg olivines and clinopyroxenes represent basaltic magma intruded into the mush. The nature of the crystal mush was closely investigated through the detailed analysis of the crystal clots found often in the Ciomadul dacites. Their texture resembles plutonic rocks, but they contain interstitial vesiculated glasses. The glass could

  11. Comparison of a chlorhexidine and a benzoyl peroxide shampoo as sole treatment in canine superficial pyoderma.

    PubMed

    Loeffler, A; Cobb, M A; Bond, R

    2011-09-03

    The clinical and antibacterial efficacy of two shampoos used as a sole antibacterial treatment in dogs with superficial pyoderma were investigated and compared. In a randomised, partially blinded study, a 3 per cent chlorhexidine gluconate shampoo (Chlorhex 3; Leo Animal Health) was compared against a 2.5 per cent benzoyl peroxide shampoo (Paxcutol; Virbac) in 22 dogs with superficial pyoderma. Dogs were washed two to three times weekly with a 10-minute contact time over 21 days. Clinical scores and bacterial counts were assessed on days 1, 8 and 22 and compared within and between treatment groups; overall response was assessed at the end of the study. Twenty dogs completed the study; 15 (68.2 per cent) showed an overall clinical improvement and the clinical signs resolved in three chlorhexidine-treated dogs. In the chlorhexidine-treated group, scores for papules/pustules (P<0.001), investigator-assessed pruritus (P=0.003), total bacterial counts (P=0.003) and counts for coagulase-positive staphylococci (P=0.003) were reduced after three weeks. Scores and bacterial counts did not vary significantly in the benzoyl peroxide-treated group.

  12. Evidence that proliferation of golgi apparatus depends on both de novo generation from the endoplasmic reticulum and formation from pre-existing stacks during the growth of tobacco BY-2 cells.

    PubMed

    Abiodun, Moses Olabiyi; Matsuoka, Ken

    2013-04-01

    In higher plants, the numbers of cytoplasmic-distributed Golgi stacks differ based on function, age and cell type. It has not been clarified how the numbers are controlled, whether all the Golgi apparatus in a cell function equally and whether the increase in Golgi number is a result of the de novo formation from the endoplasmic reticulum (ER) or fission of pre-existing stacks. A tobacco prolyl 4-hydroxylase (NtP4H1.1), which is a cis-Golgi-localizing type II membrane protein, was tagged with a photoconvertible fluorescent protein, mKikGR (monomeric Kikume green red), and expressed in tobacco bright yellow 2 (BY-2) cells. Transformed cells were exposed to purple light to convert the fluorescence from green to red. A time-course analysis after the conversion revealed a progressive increase in green puncta and a decrease in the red puncta. From 3 to 6 h, we observed red, yellow and green fluorescent puncta corresponding to pre-existing Golgi; Golgi containing both pre-existing and newly synthesized protein; and newly synthesized Golgi. Analysis of the number and fluorescence of Golgi at different phases of the cell cycle suggested that an increase in Golgi number with both division and de novo synthesis occurred concomitantly with DNA replication. Investigation with different inhibitors suggested that the formation of new Golgi and the generation of Golgi containing both pre-existing and newly synthesized protein are mediated by different machineries. These results and modeling based on quantified results indicate that the Golgi apparatuses in tobacco BY-2 cells are not uniform and suggest that both de novo synthesis from the ER and Golgi division contribute almost equally to the increase in proliferating cells.

  13. Insertion sequence IS256 in canine pyoderma isolates of Staphylococcus pseudintermedius associated with antibiotic resistance.

    PubMed

    Casagrande Proietti, P; Bietta, A; Coletti, M; Marenzoni, M L; Scorza, A V; Passamonti, F

    2012-06-15

    Staphylococcus pseudintermedius is the most frequent staphylococcal species isolated from canine pyoderma. The control of S. pseudintermedius infection is often difficult due to the expanded antimicrobial resistance phenotypes. Antibiotic resistance in staphylococcal pathogens is often associated to mobile genetic elements such as the insertion sequence IS256 that was first described as a part of the transposon Tn4001, which confers aminoglycoside resistance in Staphylococcus aureus and in Staphylococcus epidermidis. In this study a collection of 70 S. pseudintermedius isolates from canine pyoderma was used to investigate antimicrobial susceptibility to 15 antibiotics and the presence of IS256, not revealed in S. pseudintermedius yet. Antibiotic resistance profiling demonstrated that all S. pseudintermedius isolates had a multi-drug resistance phenotype, exhibiting simultaneous resistance to at least five antibiotics; indeed methicillin resistant S. pseudintermedius isolates were simultaneously resistant to at least nine antibiotics and all were also gentamicin resistant. PCR analyses revealed the presence of IS256 in 43/70 S. pseudintemedius isolates. The association between the presence of IS256 and the resistance was particularly significant for certain antibiotics: cefovecin, amikacin, gentamicin and oxacillin (χ(2)p-value<0.05). However, there was a striking result in frequency of strains resistant to gentamicin and oxacillin, suggesting a specific association between the presence of the IS256 element and the determinants for the resistance to these antibiotics. To the best of our knowledge, this is the first report showing the detection of IS256 in S. pseudintermedius isolates and its association with antibiotic resistance. Our findings suggest that S. pseudintermedius may acquire antibiotic resistance genes through mobile genetic elements which may play a predominant role in the dissemination of multi-drug resistance.

  14. A case of blastomycosis-like pyoderma caused by mixed infection of Staphylococcus epidermidis and Trichophyton rubrum.

    PubMed

    Ouchi, Takeshi; Tamura, Mai; Nishimoto, Shuhei; Sato, Tomotaka; Ishiko, Akira

    2011-06-01

    Blastomycosis-like pyoderma (BLP) is a type of chronic pyoderma characterized histologically by specific epidermal changes namely: pseudoepitheliomatous hyperplasia and intraepithelial abscesses. These epidermal changes are also seen in blastomycosis (referred to as deep dermatophytosis in North America). Here, we describe the case of a 53-year-old male with prurigo nodularis, diabetes, and chronic lymphocytic leukemia who presented with multiple yellowish-red colored papules that coalesced to form a vegetating plaque. In addition to the typical features of BLP, spores with budding were seen histopathologically in a biopsy specimen. Cultures of a skin specimen grew Staphylococcus epidermidis and Trichophyton rubrum. Antibiotic therapy was effective but failed to eliminate the lesion until antifungal therapy using terbinafine was administered concurrently. Past reports suggest that BLP is mainly caused by bacterial infection, but our case suggests that fungal infection can also be involved as the causative organism in BLP.

  15. Characterization of meticillin-resistant and meticillin-susceptible isolates of Staphylococcus pseudintermedius from cases of canine pyoderma in Australia.

    PubMed

    Siak, Meng; Burrows, Amanda K; Coombs, Geoffrey W; Khazandi, Manouchehr; Abraham, Sam; Norris, Jacqueline M; Weese, J Scott; Trott, Darren J

    2014-09-01

    Meticillin-resistant Staphylococcus pseudintermedius (MRSP) has recently emerged as a worldwide cause of canine pyoderma. In this study, we characterized 22 S. pseudintermedius isolates cultured from 19 dogs with pyoderma that attended a veterinary dermatology referral clinic in Australia in 2011 and 2012. Twelve isolates were identified as MRSP by mecA real-time PCR and phenotypic resistance to oxacillin. In addition to β-lactam resistance, MRSP isolates were resistant to erythromycin (91.6 %), gentamicin (83.3 %), ciprofloxacin (83.3 %), chloramphenicol (75 %), clindamycin (66 %), oxytetracycline (66 %) and tetracycline (50 %), as shown by disc-diffusion susceptibility testing. Meticillin-susceptible S. pseudintermedius isolates only showed resistance to penicillin/ampicillin (90 %) and tetracycline (10 %). PFGE using the SmaI restriction enzyme was unable to type nine of the 12 MRSP isolates. However the nine isolates provided the same PFGE pulsotype using the Cfr91 restriction enzyme. Application of the mec-associated direct repeat unit (dru) typing method identified the nine SmaI PFGE-untypable isolates as dt11cb, a dru type that has only previously been associated with MRSP sequence type (ST)45 isolates that possess a unique SCCmec element. The dt11cb isolates shared a similar multidrug-resistant antibiogram phenotype profile, whereas the other MRSP isolates, dt11a, dt11af (dt11a-associated) and dt10h, were resistant to fewer antibiotic classes and had distinct PFGE profiles. This is the first report of MRSP causing pyoderma in dogs from Australia. The rapid intercontinental emergence and spread of multidrug-resistant MRSP strains confirms the urgent need for new treatment modalities for recurrent canine pyoderma in veterinary practice.

  16. Characterization of a New Epidemic Necrotic Pyoderma in Fur Animals and Its Association with Arcanobacterium phocae Infection

    PubMed Central

    Nordgren, Heli; Aaltonen, Kirsi; Sironen, Tarja; Kinnunen, Paula M.; Kivistö, Ilkka; Raunio-Saarnisto, Mirja; Moisander-Jylhä, Anna-Maria; Korpela, Johanna; Kokkonen, Ulla-Maija; Hetzel, Udo; Sukura, Antti; Vapalahti, Olli

    2014-01-01

    A new type of pyoderma was detected in Finnish fur animals in 2007. The disease continues to spread within and between farms, with severe and potentially fatal symptoms. It compromises animal welfare and causes considerable economic losses to farmers. A case-control study was performed in 2010–2011 to describe the entity and to identify the causative agent. Altogether 99 fur animals were necropsied followed by pathological and microbiological examination. The data indicated that the disease clinically manifests in mink (Neovison vison) by necrotic dermatitis of the feet and facial skin. In finnraccoons (Nyctereutes procyonoides), it causes painful abscesses in the paws. Foxes (Vulpes lagopus) are affected by severe conjunctivitis and the infection rapidly spreads to the eyelids and facial skin. A common finding at necropsy was necrotic pyoderma. Microbiological analysis revealed the presence of a number of potential causative agents, including a novel Streptococcus sp. The common finding from all diseased animals of all species was Arcanobacterium phocae. This bacterium has previously been isolated from marine mammals with skin lesions but this is the first report of A. phocae isolated in fur animals with pyoderma. The results obtained from this study implicate A. phocae as a potential causative pathogen of fur animal epidemic necrotic pyoderma (FENP) and support observations that the epidemic may have originated in a species -shift of the causative agent from marine mammals. The variable disease pattern and the presence of other infectious agents (in particular the novel Streptococcus sp.) suggest a multifactorial etiology for FENP, and further studies are needed to determine the environmental, immunological and infectious factors contributing to the disease. PMID:25302603

  17. The prevalence of the pre-existing hepatitis C viral variants and the evolution of drug resistance in patients treated with the NS3-4a serine protease inhibitor telaprevir

    SciTech Connect

    Rong, Libin; Ribeiro, Ruy M; Perelson, Alan S

    2008-01-01

    Telaprevir (VX-950), a novel hepatitis C virus (HCV) NS3-4A serine protease inhibitor, has demonstrated substantial antiviral activity in patients infected with HCV genotype 1. Some patients experience viral breakthrough, which has been shown to be associated with emergence of telaprevir-resistant HCV variants during treatment. The exact mechanisms underlying the rapid selection of drug resistant viral variants during dosing are not fully understood. In this paper, we develop a two-strain model to study the pre-treatment prevalence of the mutant virus and derive an analytical solution of the mutant frequency after administration of the protease inhibitor. Our analysis suggests that the rapid increase of the mutant frequency during therapy is not due to mutant growth but rather due to the rapid and profound loss of wild-type virus, which uncovers the pre-existing mutant variants. We examine the effects of backward mutation and hepatocyte proliferation on the pre-existence of the mutant virus and the competition between wild-type and drug resistant virus during therapy. We then extend the simple model to a general model with multiple viral strains. Mutations during therapy do not play a significant role in the dynamics of various viral strains, although they are capable of generating low levels of HCV variants that would otherwise be completely suppressed because of fitness disadvantages. Hepatocyte proliferation may not affect the pretreatment frequency of mutant variants, but is able to influence the quasispecies dynamics during therapy. It is the relative fitness of each mutant strain compared with wild-type that determines which strain(s) will dominate the virus population. The study provides a theoretical framework for exploring the prevalence of pre-existing mutant variants and the evolution of drug resistance during treatment with other protease inhibitors or HCV polymerase inhibitors.

  18. Detection of antibody responses against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins in children with community-acquired pneumonia: effects of combining pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness.

    PubMed

    Borges, I C; Andrade, D C; Vilas-Boas, A-L; Fontoura, M-S H; Laitinen, H; Ekström, N; Adrian, P V; Meinke, A; Cardoso, M-R A; Barral, A; Ruuskanen, O; Käyhty, H; Nascimento-Carvalho, C M

    2015-08-01

    We evaluated the effects of combining different numbers of pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness on the detection of IgG responses against eight Streptococcus pneumoniae proteins, three Haemophilus influenzae proteins, and five Moraxella catarrhalis proteins in 690 children aged <5 years with pneumonia. Serological tests were performed on acute and convalescent serum samples with a multiplexed bead-based immunoassay. The median sampling interval was 19 days, the median age was 26.7 months, and the median duration of illness was 5 days. The rate of antibody responses was 15.4 % for at least one pneumococcal antigen, 5.8 % for H. influenzae, and 2.3 % for M. catarrhalis. The rate of antibody responses against each pneumococcal antigen varied from 3.5 to 7.1 %. By multivariate analysis, pre-existing antibody levels showed a negative association with the detection of antibody responses against pneumococcal and H. influenzae antigens; the sampling interval was positively associated with the detection of antibody responses against pneumococcal and H. influenzae antigens. A sampling interval of 3 weeks was the optimal cut-off for the detection of antibody responses against pneumococcal and H. influenzae proteins. Duration of illness was negatively associated with antibody responses against PspA. Age did not influence antibody responses against the investigated antigens. In conclusion, serological assays using combinations of different pneumococcal proteins detect a higher rate of antibody responses against S. pneumoniae compared to assays using a single pneumococcal protein. Pre-existing antibody levels and sampling interval influence the detection of antibody responses against pneumococcal and H. influenzae proteins. These factors should be considered when determining pneumonia etiology by serological methods in children.

  19. Towards ethical guidelines for dealing with unsolicited patient emails and giving teleadvice in the absence of a pre-existing patient-physician relationship — systematic review and expert survey

    PubMed Central

    2000-01-01

    Background Many health information providers on the Internet and doctors with email accounts are confronted with the phenomenon of receiving unsolicited emails from patients asking for medical advice. Also, a growing number of websites offer "ask-the-doctor" services, where patients can ask questions to health professionals via email or other means of telecommunication. It is unclear whether these types of interactions constitute medical practice, and whether physicians have the ethical obligation to respond to unsolicited patient emails. Objective To improve the quality of online communication between patients and health professionals (physicians, experts) in the absence of a pre-existing patient-physician relationship or face-to-face communication, by preparing a set of guiding ethical principles applicable to this kind of interaction. Methods Systematic review of the literature, professional, and ethical codes; and consultation with experts. Results Two different types of patient-physician encounters have to be distinguished. "Traditional" clinical encounters or telemedicine applications are called "Type B" interactions here (Bona fide relationship). In comparison, online interactions lack many of the characteristics of bona fide interactions; most notably there is no pre-existing relationship and the information available to the physician is limited if, for example, a physician responds to the email of a patient who he has never seen before. I call these "Type A" consultations (Absence of pre-existing patient-physician relationship). While guidelines for Type B interactions on the Internet exist (Kane, 1998), this is not the case for Type A interactions. The following principles are suggested: Physicians responding to patients' requests on the Internet should act within the limitations of telecommunication services and keep the global nature of the Internet in mind; not every aspect of medicine requires face-to-face communication; requests for help, including

  20. Ecthyma gangrenosum following toxic epidermal necrolysis syndrome in a 3-year-old boy-a survivable series of events.

    PubMed

    Gresik, Christine M; Brewster, Luke P; Abood, Gerard; Supple, Kathy G; Silver, Geoffrey M; Gamelli, Richard L; Nickoloff, Brian J

    2008-01-01

    Toxic epidermal necrolysis syndrome (TENS) is a severe but rare skin reaction leading to epidermal desquamation of greater than 30% of the TBSA. It is most commonly precipitated by the administration of medication. Frequent complications of this syndrome include local wound infections, respiratory, mucocutaneous, and ocular complications. Ecthyma gangrenosum (EG) is a rare disease characterized by a milliary seeding of the cutaneous tissue with Gram-negative bacteria; it is most commonly seen in immunocompromised individuals. Here we report a 3-year-old boy who developed EG subsequent to TENS. Although he had a complicated and prolonged hospital course, he survived these series of events. To our knowledge, this is the first reported case of TENS/EG in the pediatric population, and the first report of survivability following these illnesses.

  1. A case of antibacterial-responsive mucocutaneous disease in a seven-year-old dwarf lop rabbit (Oryctolagus cuniculus) resembling mucocutaneous pyoderma of dogs.

    PubMed

    Benato, L; Stoeckli, M R; Smith, S H; Dickson, S; Thoday, K L; Meredith, A

    2013-04-01

    A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was referred with severe swelling and erythema of the mucocutaneous junctions of the lips, nares and vulva. Bilateral, severe periocular dermatitis was also present. Heavy pure growths of a member of the Staphylococcus intermedius group were cultured from nasal and aural swabs and skin biopsies. Other possible differential diagnoses were eliminated by standard tests. The clinical features and histopathological characteristics of the biopsies were most consistent with mucocutaneous pyoderma, a dermatosis previously reported in dogs but not in rabbits. Treatment of the bacterial infection with oral marbofloxacin and topical ofloxacin eye drops together with supportive therapy resulted in resolution of the lesions. To the authors' knowledge, this is the first report of mucocutaneous bacterial pyoderma, similar to mucocutaneous pyoderma of dogs, in a rabbit.

  2. Streptococcal Immunity Is Constrained by Lack of Immunological Memory following a Single Episode of Pyoderma

    PubMed Central

    Pandey, Manisha; Ozberk, Victoria; Calcutt, Ainslie; Langshaw, Emma; Powell, Jessica; Rivera-Hernandez, Tania; Philips, Zachary; Batzloff, Michael R.; Good, Michael F.

    2016-01-01

    The immunobiology underlying the slow acquisition of skin immunity to group A streptococci (GAS), is not understood, but attributed to specific virulence factors impeding innate immunity and significant antigenic diversity of the type-specific M-protein, hindering acquired immunity. We used a number of epidemiologically distinct GAS strains to model the development of acquired immunity. We show that infection leads to antibody responses to the serotype-specific determinants on the M-protein and profound protective immunity; however, memory B cells do not develop and immunity is rapidly lost. Furthermore, antibodies do not develop to a conserved M-protein epitope that is able to induce immunity following vaccination. However, if re-infected with the same strain within three weeks, enduring immunity and memory B-cells (MBCs) to type-specific epitopes do develop. Such MBCs can adoptively transfer protection to naïve recipients. Thus, highly protective M-protein-specific MBCs may never develop following a single episode of pyoderma, contributing to the slow acquisition of immunity and to streptococcal endemicity in at-risk populations. PMID:28027314

  3. Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.

    PubMed

    Zur, Gila; Soback, Stefan; Weiss, Yfat; Perry, Elad; Lavy, Eran; Britzi, Malka

    2014-04-01

    Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 μg/mL and 1.03 ± 0.43 μg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2).

  4. Clinical Safety and Efficacy of Nilotinib or Dasatinib in Patients with Newly Diagnosed Chronic-Phase Chronic Myelogenous Leukemia and Pre-existing Liver and/or Renal Dysfunction

    PubMed Central

    Sasaki, Koji; Lahoti, Amit; Jabbour, Elias; Jain, Preetesh; Pierce, Sherry; Borthakur, Gautam; Daver, Naval; Kadia, Tapan; Pemmaraju, Naveen; Ferrajoli, Alessandra; O’Brien, Susan; Kantarjian, Hagop; Cortes, Jorge

    2016-01-01

    Summary BACKGROUND The safety and efficacy of frontline nilotinib and dasatinib in newly diagnosed chronic-phase chronic myelogenous leukemia (CML-CP) patients with pre-existing liver and/or renal dysfunction are unknown. PATIENTS and METHODS We analyzed adverse event rates, response rates, and survival rates of 215 CML-CP patients with or without renal and/or liver dysfunction who were treated with front-line nilotinib (108 patients) or dasatinib (107 patients). RESULTS Overall median follow-up was 49 months. At baseline, 6 (6%) dasatinib-treated patients had mild renal dysfunction and 13 (12%) had mild liver dysfunction. Eight (7%) nilotinib-treated patients had mild renal dysfunction, 1 (1%) had moderate renal dysfunction, and 9 (8%) mild liver dysfunction. There were no significant differences in the rates of complete cytogenetic response, major molecular response, or MR4.5 between organ function cohorts. Dasatinib- or nilotinib- treated patients with baseline renal dysfunction had a higher incidence of transient reversible acute kidney injury (p=0.011; p<0.001), and nilotinib-treated patients with renal dysfunction had a higher incidence of bleeding (p<0.001). CONCLUSION CML-CP patients with mild to moderate renal or liver dysfunction can be safely treated with frontline dasatinib or nilotinib and can achieve response rates similar to those of CML-CP patients with normal organ function. PMID:26796981

  5. Novel application of stereotactic ablative radiotherapy using CyberKnife(®) for early-stage renal cell carcinoma in patients with pre-existing chronic kidney disease: Initial clinical experiences.

    PubMed

    Lo, Cheng-Hsiang; Huang, Wen-Yen; Chao, Hsing-Lung; Lin, Kuen-Tze; Jen, Yee-Min

    2014-07-01

    The treatment of renal cell carcinoma (RCC) in patients diagnosed with chronic kidney disease (CKD) requires particular care in order to preserve the remaining renal function. The present study aimed to investigate the potential of a novel nephron-sparing treatment, which is capable of targeting tumors embedded deep within tissues. The present study analyzed three patients, with pre-existing CKD and multiple comorbidities, who were successfully treated for stage I RCC using the CyberKnife(®) stereotactic ablative radiotherapy (SABR) system. The total prescribed dose was 40 Gy in five fractions administered over five consecutive days. Treatment efficiency was determined using computed tomography scans of the tumors and periodic measurements of the glomerular filtration rate over a period of 12-40 months. Local control, defined as a radiologically stable condition, was achieved in all patients. Lung metastasis was observed in one patient nine months after SABR; however, the side-effects were generally mild and self-limiting. One patient developed renal failure 26 months after SABR, while the severity of CKD was only marginally altered in the other two patients and renal failure did not occur. In conclusion, in the present study, SABR with CyberKnife(®) was observed to be well tolerated in the patients, with an acceptable acute toxicity effect. Therefore, it may represent a potential therapeutic option for patients with early-stage RCC who have previously been diagnosed with CKD, but for whom other nephron-sparing treatments are contraindicated.

  6. A study of community-associated methicillin-resistant Staphylococcus aureus in patients with pyoderma

    PubMed Central

    Venniyil, Prasanth V.; Ganguly, Satyaki; Kuruvila, Sheela; Devi, Sheela

    2016-01-01

    Background: Health care–associated methicillin-resistant Staphylococcus aureus(HA-MRSA) are resistant to multiple antibiotics, therefore infections caused by them are difficult to treat resulting in high morbidity and mortality. While most of the research activities and public health initiatives are focused on HA-MRSA, the newly emerging pathogen, community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) is gaining in significance in respect to patient morbidity. There is a significant paucity of data regarding CA-MRSA in the developing parts of the world. Aim: To study the proportions of HA-MRSA and CA-MRSA infections among patients with culture-proven S. aureus infection and to find out how many of these patients showed presence of MRSA in nasal cultures of healthy contacts. Materials and Methods: Clinical details of 227 patients were recorded in the study, such as the duration and recurrence of the infection, history of antibiotic intake, and the presence of other medical illnesses. A pus swab was taken from each lesion and sent for culture and sensitivity. If the culture grew S. aureus, they were screened for methicillin resistance. A swab from the anterior nares of the healthy contact of each patient, whenever available, was collected and it was screened for MRSA. Results: Furunculosis was most common among the primary pyodermas (53/134; 39. 5%). Out of 239 pus culture samples obtained from 227 patients, 192 (84.58%) grew S. aureus; of these 150 (78.12%) were methicillin-sensitive S. aureus (MSSA), whereas 42 (21.98%) were MRSA. Out of the 42 MRSA isolated, 33 turned out to be CA-MRSA (78%) and 9 (22%) were HA-MRSA. Nasal swabs of healthy contacts of 34 MRSA patients were cultured. Out of them, two grew MRSA in the culture. Conclusion: The isolation rate of S. aureus was high in our study. Furthermore, our study, although hospital based, clearly indicated the substantial magnitude of the CA-MRSA problem in the local population. PMID:27294048

  7. Influence of pre-existing fabrics on fault kinematics and rift geometry of interacting segments: Analogue models based on the Albertine Rift (Uganda), Western Branch-East African Rift System

    NASA Astrophysics Data System (ADS)

    Aanyu, K.; Koehn, D.

    2011-02-01

    This study aims at showing how far pre-existing crustal weaknesses left behind by Proterozoic mobile belts, that pass around cratonic Archean shields (Tanzania Craton to the southeast and Congo Craton to the northwest), control the geometry of the Albertine Rift. Focus is laid on the development of the Lake Albert and Lake Edward/George sub-segments and between them the greatly uplifted Rwenzori Mountains, a horst block located within the rift and whose highest peak rises to >5000 m above mean sea level. In particular we study how the southward propagating Lake Albert sub-segment to the north interacts with the northward propagating Lake Edward/George sub-segment south of it, and how this interaction produces the structures and geometry observed in this section of the western branch of the East African Rift, especially within and around the Rwenzori horst. We simulate behaviour of the upper crust by conducting sandbox analogue experiments in which pre-cut rubber strips of varying overstep/overlap connected to a basal sheet and oriented oblique and/or orthogonal to the extension vector, are placed below the sand-pack. The points of connection present velocity discontinuities to localise deformation, while the rubber strips represent ductile domain affected by older mobile belts. From fault geometry of developing rift segments in plan view and section cuts, we study kinematics resulting from a given set of boundary conditions, and results are compared with the natural scenario. Three different basal model-configurations are used to simulate two parallel rifts that propagate towards each other and interact. Wider overstep (model SbR3) produces an oblique transfer zone with deep grabens (max. 7.0 km) in the adjoining segments. Smaller overlap (model SbR4) ends in offset rift segments without oblique transfer faults to join the two, and produces moderately deep grabens (max. 4.6 km). When overlap doubles the overstep (model SbR5), rifts propagate sub-orthogonal to the

  8. Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals.

    PubMed

    Balotta, C; Berlusconi, A; Pan, A; Violin, M; Riva, C; Colombo, M C; Gori, A; Papagno, L; Corvasce, S; Mazzucchelli, R; Facchi, G; Velleca, R; Saporetti, G; Galli, M; Rusconi, S; Moroni, M

    2000-03-01

    We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.

  9. Antimicrobial susceptibility and methicillin resistance in Staphylococcus pseudintermedius and Staphylococcus schleiferi subsp. coagulans isolated from dogs with pyoderma in Japan.

    PubMed

    Kawakami, Tetsuji; Shibata, Sanae; Murayama, Nobuo; Nagata, Masahiko; Nishifuji, Koji; Iwasaki, Toshiroh; Fukata, Tsuneo

    2010-12-01

    To understand species distribution, trends of antimicrobial susceptibility and prevalence of methicillin resistance in canine staphylococci in Japan, 190 coagulase-positive staphylococci (CoPS) were isolated from dogs with pyoderma in 2 Japanese veterinary referral hospitals. Using a multiplex polymerase chain reaction (M-PCR) method, two CoPS species were identified: 170 Staphylococcus pseudintermedius (89.5%) and 20 S. schleiferi subsp. coagulans isolates (10.5%). In these isolates, susceptibility to 7 antimicrobial agents was determined. Overall, the levels of susceptibility to cefalexin (CEX), amoxicillin/clavulanic acid (CVA/AMPC), minocycline (MINO), ofloxacin (OFLX), norfloxacin (NFLX), lincomycin (LCM) and clindamycin (CLDM) in S. pseudintermedius isolates were 38.2, 52.4, 34.7, 31.2, 34.1, 1.2 and 11.2%, respectively. In S. schleiferi subsp. coagulans isolates, 55% demonstrated susceptibility to CEX, 80% to CVA/AMPC, 70% to MINO, 45% to OFLX or NFLX and 30% to CLDM. None of S. schleiferi subsp. coagulans isolates was susceptible to LCM. To determine the prevalence of methicillin-resistant strains, we used a PCR method, which enabled detection of the fragment of mecA gene in 66.5% (113 of 170) in S. pseudintermedius and 30.0% (6 of 20) in S. schleiferi subsp. coagulans isolates. The frequencies of susceptibility to CEX, CVA/AMPC, OFLX, NFLX and CLDM were significantly lower in methicillin-resistant CoPS than in methicillin-susceptible CoPS isolates. These data suggest a high level of methicillin resistance in staphylococci isolated from dogs with pyoderma in Japan.

  10. 3-D numerical modelling of the influence of reactivated pre-existing faults on the distribution of deformation: example of North-Western Ghana around 2.15-2.00 Ga

    NASA Astrophysics Data System (ADS)

    FENG, Xiaojun; Gerbault, Muriel; Martin, Roland; Ganne, Jérôme; Jessell, Mark

    2015-04-01

    High strain zones appear to play a significant role in feeding the upper crust with fluids and partially molten material from lower crust sources. The Bole-Bulenga terrain (North-Western Ghana) is located in between two subvertical shear zones, and mainly consists of high-grade orthogneisses, paragneisses and metabasites intruded by partially molten lower crustal material with monzogranites and orthogneisses (Eburnean orogeny, around 2.1 Ga). In order to understand the location of these high grade rocks at the edges and in between these two shear zones, a three dimensional numerical model was built to test the influence of different orientations of a system of branched strike-slip faults on visco-plastic deformation, under compressional and simple shear boundary conditions. Our models indicate domains of tensile vs. compressional strain as well as shear zones, and show that not only internal fault zones but also the host rock in between the faults behave relatively softer than external regions. Under both applied compressive and simple shear boundary conditions, these softened domains constitute preferential zones of tensile strain accommodation (dilation) in the upper crust, which may favor infilling by deeper partially molten rocks. Our modeled pre-existing faults zones are assumed to have formed during an early D1 stage of deformation, and they are shown to passively migrate and rotate together with the solid matrix under applied external boundary conditions (corresponding to a post D1 - early D2 phase of deformation). We suggest that in the Bole-Bulenga terrain, fluids or partially molten material stored in deeper crustal domains, preferentially intruded the upper crust within these highly (shear and tensile) strained domains, thanks to this D2 shearing deformation phase. Building relief at the surface is primarily controlled by fault orientations, together with mechanical parameters and external boundary conditions. In particular, greatest magnitudes of relief

  11. Identification of a novel Staphylococcus pseudintermedius exfoliative toxin gene and its prevalence in isolates from canines with pyoderma and healthy dogs.

    PubMed

    Iyori, Keita; Hisatsune, Junzo; Kawakami, Tetsuji; Shibata, Sanae; Murayama, Nobuo; Ide, Kaori; Nagata, Masahiko; Fukata, Tsuneo; Iwasaki, Toshiroh; Oshima, Kenshiro; Hattori, Masahira; Sugai, Motoyuki; Nishifuji, Koji

    2010-11-01

    Staphylococcal exfoliative toxins are involved in some cutaneous infections in mammals by targeting desmoglein 1 (Dsg1), a desmosomal cell-cell adhesion molecule. Recently, an exfoliative toxin gene (exi) was identified in Staphylococcus pseudintermedius isolated from canine pyoderma. The aim of this study was to identify novel exfoliative toxin genes in S. pseudintermedius. Here, we describe a novel orf in the genome of S. pseudintermedius isolated from canine impetigo, whose deduced amino acid sequence was homologous to that of the SHETB exfoliative toxin from Staphylococcus hyicus (70.4%). The ORF recombinant protein caused skin exfoliation and abolished cell surface staining of Dsg1 in canine skin. Moreover, the ORF protein degraded the recombinant extracellular domains of canine Dsg1, but not Dsg3, in vitro. PCR analysis revealed that the orf was present in 23.2% (23/99) of S. pseudintermedius isolates from dogs with superficial pyoderma exhibiting various clinical phenotypes, while the occurrence in S. pseudintermedius isolates from healthy dogs was 6.1% (3/49). In summary, this newly found orf in S. pseudintermedius encodes a novel exfoliative toxin, which targets a cell-cell adhesion molecule in canine epidermis and might be involved in a broad spectrum of canine pyoderma.

  12. Experimental Infection of Mink Enforces the Role of Arcanobacterium phocae as Causative Agent of Fur Animal Epidemic Necrotic Pyoderma (FENP)

    PubMed Central

    Nordgren, Heli; Aaltonen, Kirsi; Raunio-Saarnisto, Mirja; Sukura, Antti; Vapalahti, Olli; Sironen, Tarja

    2016-01-01

    Fur Animal Epidemic Necrotic Pyoderma (FENP) is a severe, often lethal infectious disease affecting all three fur animal species: mink (Neovision vision), foxes (Vulpes lagopus) and finnraccoons (Nyctereutes procyonoides). Previous studies showed an association between Arcanobacterium phocae and FENP. An experimental infection was conducted to confirm the ability of A. phocae to infect mink either alone or concurrently with a novel Streptococcus sp. found together with A. phocae in many cases of FENP. Different inoculation methods were tested to study possible routes of transmission. Typical signs, and gross- and histopathological findings for FENP were detected when naïve mink were infected with the tissue extract of mink with FENP, using a subcutaneous/ intradermal infection route. Edema, hemorrhage, necrosis and pus formation were detected in the infection site. A pure culture preparation of A. phocae alone or concurrently with the novel Streptococcus sp. caused severe acute signs of lethargy, apathy and anorexia and even mortality. The histopathological findings were similar to those found in naturally occurring cases of FENP. In contrast, the perorally infected mink presented no clinical signs nor any gross- or histopathological lesions. This study showed that A. phocae is able to cause FENP. The study also indicated that predisposing factors such as the environment, the general condition of the animals, temperature and skin trauma contribute to the development of the disease. PMID:27973532

  13. Investigations into the basis of chloramphenicol and tetracycline resistance in Staphylococcus intermedius isolates from cases of pyoderma in dogs.

    PubMed

    Kim, T J; Na, Y R; Lee, J I

    2005-04-01

    A total of 160 Staphylococcus intermedius isolates were recovered from cases of pyoderma in 2002 and were examined for susceptibility to 13 different antimicrobial agents. Ninety per cent (144) of the isolates were resistant to tetracycline, derivatives of which have been used until recently, and 18% (29) were resistant to chloramphenicol which was banned from use 13 years ago. The presence of genes encoding chloramphenicol acetyltransferase (CAT) and tetracycline resistance (tet); tet(K), (L), (M), and (O) were determined by PCR in the 29 chloramphenicol and tetracycline resistant isolates. Seventeen (59%) isolates contained the cat gene while 12 (41%) isolates did not carry the cat gene, implying there may be other genes for chloramphenicol resistance that were not detected by the primers (primer set 1) used in this study. The tet(M) gene was found in 28 (97%) of the resistant S. intermedius isolates, but none contained the tet(O) gene. All 29 isolates carried one or two tet genes; tet(K), (L), and (M), with four different distribution patterns. New PCR products, a 1.1 kb product using primer set 1 and a 0.2 kb product using primer set 2, were cloned and sequenced. A 904 bp fragment of S. aureus plamid pS194, including sequence from the streptomycin adenyltransferase gene (804 bp), was found inserted into the terminal region of the cat gene (GenBank accession no. AY604739), whilst the sequence of 0.2 kb was previously unpublished.

  14. High prevalence of Fluoroquinolone- and Methicillin-resistant Staphylococcus pseudintermedius isolates from canine pyoderma and otitis externa in veterinary teaching hospital.

    PubMed

    Yoo, Jong-Hyun; Yoon, Jang W; Lee, So-Young; Park, Hee-Myung

    2010-04-01

    Recently, a total of 74 Staphylococcus pseudintermedius isolates were collected from clinical cases of canine pyoderma and otitis externa in Korea. In this study, we examined in vitro fluoroquinolone resistance among those isolates using a standard disk diffusion technique. The results demonstrated that approximately 18.9% to 27.0% of the isolates possessed bacterial resistance to both veterinary- and human-licensed fluoroquinolones except one isolate, including moxifloxacin (18.9% resistance), levofloxacin (20.3% resistance), ofloxacin (24.3% resistance), ciprofloxacin (25.7% resistance), and enrofloxacin (27.0% resistance). Most surprisingly, 14 out of 74 (18.9%) isolates were resistant to all the five fluoroquinolones evaluated. Moreover, a PCR detection of the methicillin resistance gene (mecA) among the 74 isolates revealed that 13 out of 25 (52.0%) mecA-positive isolates, but only 7 out of 49 (14.3%) mecA-negative isolates, were resistant to one or more fluoroquinones. Taken together, our results imply that bacterial resistance to both veterinary- and human-use fluoroquinolones becomes prevalent among the S. pseudintermedius isolates from canine pyoderma and otitis externa in Korea as well as that the high prevalence of the mecA-positive S. pseudintermedius isolates carrying multiple fluoroquinolone resistance could be a potential public health problem.

  15. Staphylococcus pseudintermedius and Staphylococcus schleiferi Subspecies coagulans from Canine Pyoderma Cases in Grenada, West Indies, and Their Susceptibility to Beta-Lactam Drugs.

    PubMed

    Hariharan, Harry; Gibson, Kathryn; Peterson, Ross; Frankie, Matthew; Matthew, Vanessa; Daniels, Joshua; Martin, Nancy A; Andrews, Linton; Paterson, Tara; Sharma, Ravindra N

    2014-01-01

    Over a 2-year period 66 cases of canine pyoderma in Grenada, West Indies, were examined by aerobic culture in order to ascertain the bacteria involved and their antimicrobial resistance patterns. Of the 116 total bacterial isolates obtained, the majority belonged to Gram-positive species, and the most common organism identified through biochemical and molecular methods was Staphylococcus pseudintermedius. Additionally, identification of a Staphylococcus schleiferi subspecies coagulans isolate was confirmed by molecular methods. All isolates of staphylococci were susceptible to beta-lactam drugs: amoxicillin-clavulanic acid, cefovecin, cefoxitin, cefpodoxime, and cephalothin. They were also susceptible to chloramphenicol and enrofloxacin. Resistance was highest to tetracycline. Methicillin resistance was not detected in any isolate of S. pseudintermedius or in S. schleiferi. Among the Gram-negative bacteria, the most common species was Klebsiella pneumoniae, followed by Acinetobacter baumannii/calcoaceticus. The only drug to which all Gram-negative isolates were susceptible was enrofloxacin. This report is the first to confirm the presence of S. pseudintermedius and S. schleiferi subspecies coagulans, in dogs with pyoderma in Grenada, and the susceptibility of staphylococcal isolates to the majority of beta-lactam drugs used in veterinary practice.

  16. A synthetic M protein peptide synergizes with a CXC chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia.

    PubMed

    Pandey, Manisha; Langshaw, Emma; Hartas, Jon; Lam, Alfred; Batzloff, Michael R; Good, Michael F

    2015-06-15

    Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain's ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100-1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.

  17. 78 FR 30218 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... Plan using the current cost sharing rules described in the Plan brochure. Furthermore, to protect... the remainder, as calculated by the Plan using the current cost sharing rules described in the Plan... drugs is not administratively feasible or cost effective. Therefore, the current plan allowances...

  18. Pre-existing Condition Patient Protection Act of 2009

    THOMAS, 111th Congress

    Sen. Rockefeller, John D., IV [D-WV

    2009-03-17

    03/17/2009 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (text of measure as introduced: CR S3183-3185) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. 75 FR 45013 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    ... that of FEHBP. The subject of Federal funding of abortion services with respect to the Affordable Care... abortion services, except in cases of rape or incest, or where the life of the woman would be endangered... the PCIP program shall not include abortion services except in the case of rape or incest, or...

  20. 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

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE... rights of subsistence use or access in existence on the date of designation of any National Marine... date of Sanctuary designation, or in the case of the Florida Keys National Marine Sanctuary...

  1. [Multiple abscesses after a cruise along the Latin American coast].

    PubMed

    Reynolds, C; Schofer, N; Zengin, E; Lohse, A W; Faiss, S; Schmiedel, S

    2016-03-01

    We report a case of an extracutaneous involvement of pyoderma gangrenosum. The patient initially presented with multiple sterile abscesses of the skin, heart, prostate, and kidney. Extracutaneous involvement in pyoderma gangrenosum is very rare. Confirmation of the diagnosis was only possible after exclusion of other relevant differential diagnoses. Continuous search for microbes proved negative and after an empiric therapeutic attempt with prednisolone, the patient improved quickly. However, each time we reduced the steroids even in combination with methotrexate or with azathioprine the patient relapsed. Only after therapy with the tumor necrosis factor-α-inhibitor infliximab was permanent remission achieved.

  2. Management of neutrophilic dermatoses.

    PubMed

    Schadt, Courtney R; Callen, Jeffrey P

    2012-01-01

    Neutrophilic dermatoses, including Sweet's syndrome, pyoderma gangrenosum, and rheumatoid neutrophilic dermatitis, are inflammatory conditions of the skin often associated with underlying systemic disease. These are characterized by the accumulation of neutrophils in the skin. The associated conditions, potential for systemic neutrophilic infiltration, and therapeutic management of these disorders can be similar. Sweet's syndrome can often be effectively treated with a brief course of systemic corticosteroids. Pyoderma gangrenosum, however, can be recurrent, and early initiation of a steroid-sparing agent is prudent. Second-line treatment for both of these conditions includes medications affecting neutrophil function, in addition to immunosuppressant medications.

  3. Medical Planning Criteria for Implementation of Clinical Hyperbaric Facilities.

    DTIC Science & Technology

    1984-12-01

    Fracture healing 90.0 25 Burns 66.5 32 Radiation enteritis/myelitis/proctitis 70.0 34 Skin grafts/flaps, compromised 93.5 0 39 Necrotizing fasciitis 83.5...Hydrogen sulfide poisoning, acute 39. Necrotizing fasciitis 40. Pneumocystosis _ 41. Pseudomembranous colitis 42. Pyoderma gangrenosum 41...Hydrogen sulfide poisoning, acute 98780 39. Necrotizing fasciitis - 729410 410. Pneuinocystosis 13630 41. Pseudomembranous colitis 561410 * 42. Pyoderma

  4. Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

    PubMed

    Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M

    2015-06-24

    A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  5. Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm.

    PubMed

    Khatibi, Kasra; Heit, Jeremy J; Telischak, Nicholas A; Elbers, Jorina M; Do, Huy M

    2016-08-01

    A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.

  6. Investigation of the clinical efficacy of 0.2% topical stannous fluoride for the treatment of canine superficial pyoderma: a prospective, randomized, double-blinded, placebo-controlled trial.

    PubMed

    Seltzer, Judith D; Flynn-Lurie, Alison K; Marsella, Rosanna; Brennan, Meghan M

    2010-06-01

    Stannous fluoride (SF) is an antibacterial compound that has been successfully used to treat gingivitis in people and dogs, and cutaneous bacterial infections in horses. The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of 0.2% SF spray (BacDerm; Emerald 3 Enterprises Inc., Camdenton, MO, USA) for the treatment of canine superficial pyoderma. Twenty-six privately owned dogs with bacterial skin infections diagnosed on clinical signs, cytology and aerobic culture were enrolled. Dogs were randomly assigned to vehicle only or active ingredient treatment groups. The product was applied topically to affected areas once daily for 28 days, with assessments at days 0, 14, 28 and 42. Clinical and cytological evaluations were performed by the same investigators at each visit. Owners scored the improvement of hair coat, odour, pruritus and overall improvement at each recheck. Linear mixed models showed significant effects of treatment (P < 0.0001) and time (P = 0.0037) for investigator's scores, and a significant time effect for owners' haircoat (P = 0.0077) and odour (P = 0.0170) improvement scores. Dogs in both placebo and SF groups showed some improvement over time, and the investigator's scores on days 0 and 28 were not significantly different between groups for both (t-test P > 0.05). Spearman's rho correlation coefficients revealed a significant negative correlation between investigator's scores and all categories of owners' assessment scores in dogs of both groups. Although some dogs improved on SF, this study does not support the use of 0.2% SF as sole therapy for canine superficial pyoderma.

  7. Porphyria cutanea tarda in pre-existent lupus erythematosus--is there an association?

    PubMed

    van Tuyll van Serooskerken, Anne-Moon; Habets, J M Werner; Badeloe, Sadhanna; Poblete-Gutiérrez, Pamela; Frank, Jorge

    2007-11-01

    In lupus erythematosus (LE), vesicles and bullae are only rarely seen. However, in some instances such efflorescences might suggest an association with distinct cutaneous diseases, including erythema multiforme, toxic epidermal necrolysis or autoimmune blistering disorders such as bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis Duhring. Another blistering disease that has been described in association with cutaneous and systemic LE is porphyria cutanea tarda (PCT). PCT is a metabolic disorder caused by a deficiency of the fifth enzyme in heme biosynthesis, uroporphyrinogen decarboxylase. Here, we report on a 57-year-old Caucasian woman of Dutch origin with a medical history of mild cutaneous LE who developed skin fragility, blistering skin lesions, milia, and facial hypertrichosis. Subsequent porphyrin analysis in urine and feces confirmed the suspected simultaneous manifestation of LE and PCT.

  8. EFFECTS OF INHALED ULTRAFINE PARTICLES ON PRE-EXISTING ALLERGIC AIRWAY RESPONSES. (R826785)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  9. Pre-existing oral contrast from lanthanum carbonate: a confounding factor in CT mesenteric angiography.

    PubMed

    Bull, M D; Shrimanker, R; Thomas, M R M; Mulgrew, C J

    2012-04-01

    A 69-year-old male was referred from the renal unit to radiology for investigation of bleeding per rectum. A CT mesenteric angiogram was performed. However, it was noted on the pre-contrast images that the large bowel contained positive oral contrast media. The procedure was abandoned as it would have been difficult to see extravasation of intravenous contrast from a bleeding point in the large bowel. The initial belief was that either the patient had been given oral contrast by ward staff on the assumption that it would be needed, or had had a recent radiological study requiring contrast, which was still present. Neither was the case; it emerged that the patient was taking Fosrenol (Shire Pharmaceuticals, Wayne, PA), a lanthanum carbonate medication used in the treatment of hyperphosphataemia. Lanthanum is densely radio-opaque and appears as positive bowel contrast on CT and plain radiography studies. When considering radiological studies specifically requiring the absence of oral contrast, it is important to be aware of the patient's drug history to avoid non-diagnostic scans with the associated radiation exposure.

  10. Pelvic Arterial Embolisation in a Trauma Patient with a Pre-Existing Aortobifemoral Graft

    SciTech Connect

    Abulaban, Osama; Hopkins, Jonathan; Willis, Andrew P.; Jones, Robert G.

    2011-02-15

    Pelvic fractures secondary to blunt trauma are associated with a significant mortality rate due to uncontrolled bleeding. Interventional radiology (IR) can play an important and central role in the management of such patients, offering definitive minimally invasive therapy and avoiding the need for high-risk surgery. Rapid access to whole-body computed tomography has been shown to improve survival in polytrauma patients and allows rapid diagnosis of vascular injury and assessment of suitability for endovascular therapy. IR can then target and treat the specific area of bleeding. Embolisation of bleeding pelvic arteries has been shown to be highly effective and should be the treatment of choice in this situation. The branches of the internal iliac artery (IIA) are usually involved, and these arteries are accessed by way of IIA catheterisation after abdominal aortography. Occasionally these arteries cannot be accessed by way of this conventional route because of recent IIA ligation carried out surgically in an attempt to stop the bleeding or because (in the rare situation we describe here) these vessels are excluded secondary to previous aortoiliac repair. In this situation, knowledge of pelvic arterial collateral artery pathways is important because these will continue to supply pelvic structures whilst making access to deep pelvic branches challenging. We describe a rare case, which has not been previously reported in the literature, in which successful embolisation of a bleeding pelvic artery was carried out by way of the collateral artery pathways.

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

    SciTech Connect

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

    2015-08-12

    A long-standing objective in materials research is to find innovative ways to remove preexisting damage and heal fabrication defects or environmentally induced defects in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power, 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 processes results in a highly localized thermal spike that can effectively heal preexisting defects and restore the structural order. This work reveals an innovative self-healing process using highly ionizing ions, and it describes a critical aspect to be considered in modeling SiC performance as either a functional or a structural material for device applications or high-radiation environments.

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

    DOE PAGES

    Zhang, Yanwen; Sachan, Ritesh; Pakarinen, Olli H.; ...

    2015-08-12

    A long-standing objective in materials research is to find innovative ways to remove preexisting damage and heal fabrication defects or environmentally induced defects in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power, 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 processes results in a highly localized thermal spike that can effectively heal preexisting defects and restore the structural order. This work revealsmore » an innovative self-healing process using highly ionizing ions, and it describes a critical aspect to be considered in modeling SiC performance as either a functional or a structural material for device applications or high-radiation environments.« less

  13. Pre-Existing Venous Calcification Prior to Dialysis Vascular Access Surgery

    PubMed Central

    Lee, Timmy; Safdar, Nida; Mistry, Meenakshi J; Wang, Yang; Chauhan, Vibha; Campos, Begoña; Munda, Rino; Cornea, Virgilius; Roy-Chaudhury, Prabir

    2014-01-01

    Vascular calcification is present in arterial vessels used for dialysis vascular access creation prior to surgical creation. Calcification in the veins used to create a new vascular access has not previously been documented. The objective of this study was to describe the prevalence of venous calcification in samples collected at the time of vascular access creation. 67 vein samples were studied. A von Kossa stain was performed to quantify calcification. A semi-quantitative scoring system from 0–4+ was used to quantify the percentage positive area for calcification as a fraction of total area (0=0; 1+ = 1–10%; 2+ =11–25%; 3+ = 26–50%; 4+ >50% positive). 22/67(33%) samples showed evidence of venous calcification. Histologic examination showed varying degrees of calcification within each cell layer. Among the subset of patients with calcification, 4/22 (18%), 19/22 (86%), 22/22 (100%), and 7/22 (32%) had calcification present within the endothelium, intima, media, and adventitia, respectively. The mean semi-quantitative scores of the 22 samples with calcification were 0.18±0.08, 1.2±0.14, 1.6±0.13, and 0.36±0.12 for the endothelium, intima, media, and adventitia, respectively. Our results demonstrate that vascular calcification is present within veins used to create new dialysis vascular access, and located predominately within the neointimal and medial layers. PMID:22452638

  14. Pre-Existing Background Knowledge Influences Socioeconomic Differences in Preschoolers' Word Learning and Comprehension

    ERIC Educational Resources Information Center

    Kaefer, Tanya; Neuman, Susan B.; Pinkham, Ashley M.

    2015-01-01

    The goal of the current study is to explore the influence of knowledge on socioeconomic discrepancies in word learning and comprehension. After establishing socioeconomic differences in background knowledge (Study 1), the authors presented children with a storybook that incorporates this knowledge (Study 2). Results indicated that middle-income…

  15. The effect of pre-existing corrosion on the fatigue cracking behavior of aluminum alloys

    SciTech Connect

    Hagerdorn, E.L.; Koch, G.H.

    1996-10-01

    In order to assess the effect of preexisting corrosion on the fatigue crack behavior of aluminum alloys 2024-T3 and 7074-T6 crack initiation and growth data were obtained using fracture mechanics specimens. These specimens incorporated mechanically thinned areas and areas that had been preexposed to environments which produced various degrees of pitting or exfoliation corrosion. The data obtained from these laboratory experiments indicate that specific corrosive was most pronounced in the fatigue cracking behavior of aluminum alloys. The effect of preexisting corrosion was most pronounced in the fatigue crack initiation stage. Based on the results of this study, it was concluded that the effect of preexisting corrosion on the fatigue cracking behavior of both aluminum alloys 2024-T3 and 7075-T6 is a combination of stress concentrations as a result of material loss, and altered material properties, possible as a result of hydrogen entry into the lattice.

  16. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

    PubMed Central

    Bains, Anupama; Vedant, Deepak; Shanker, Vinay; Tegta, G. R.

    2016-01-01

    Primary cutaneous anaplastic large cell lymphoma (pcALCL) forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary. PMID:27990392

  17. Leukocytoclastic vasculitis in an adolescent with ulcerative colitis: Report of a case and review of the literature

    PubMed Central

    Butts, G Tyler; Bishop, Phyllis R; Wyatt, Julie P

    2014-01-01

    An adolescent female with long-standing, difficult-to-control ulcerative colitis developed leukocytoclastic vasculitis, a rare cutaneous extra-intestinal manifestation of the inflammatory bowel disease. The authors provide a literature review on leukocytoclastic vasculitis complicating ulcerative colitis. Furthermore, the clinical features of leukocytoclastic vasculitis are compared and contrasted with the more common cutaneous extra-intestinal manifestations of inflammatory bowel disease, erythema nodosum, and pyoderma gangrenosum. PMID:27489650

  18. The F-BAR protein PSTPIP1 controls extracellular matrix degradation and filopodia formation in macrophages

    PubMed Central

    Starnes, Taylor W.; Bennin, David A.; Bing, Xinyu; Eickhoff, Jens C.; Grahf, Daniel C.; Bellak, Jason M.; Seroogy, Christine M.; Ferguson, Polly J.

    2014-01-01

    PSTPIP1 is a cytoskeletal adaptor and F-BAR protein that has been implicated in autoinflammatory disease, most notably in the PAPA syndrome: pyogenic sterile arthritis, pyoderma gangrenosum, and acne. However, the mechanism by which PSTPIP1 regulates the actin cytoskeleton and contributes to disease pathogenesis remains elusive. Here, we show that endogenous PSTPIP1 negatively regulates macrophage podosome organization and matrix degradation. We identify a novel PSTPIP1-R405C mutation in a patient presenting with aggressive pyoderma gangrenosum. Identification of this mutation reveals that PSTPIP1 regulates the balance of podosomes and filopodia in macrophages. The PSTPIP1-R405C mutation is in the SRC homology 3 (SH3) domain and impairs Wiskott-Aldrich syndrome protein (WASP) binding, but it does not affect interaction with protein-tyrosine phosphatase (PTP)-PEST. Accordingly, WASP inhibition reverses the elevated F-actin content, filopodia formation, and matrix degradation induced by PSTPIP1-R405C. Our results uncover a novel role for PSTPIP1 and WASP in orchestrating different types of actin-based protrusions. Our findings implicate the cytoskeletal regulatory functions of PSTPIP1 in the pathogenesis of pyoderma gangrenosum and suggest that the cytoskeleton is a rational target for therapeutic intervention in autoinflammatory disease. PMID:24421327

  19. The F-BAR protein PSTPIP1 controls extracellular matrix degradation and filopodia formation in macrophages.

    PubMed

    Starnes, Taylor W; Bennin, David A; Bing, Xinyu; Eickhoff, Jens C; Grahf, Daniel C; Bellak, Jason M; Seroogy, Christine M; Ferguson, Polly J; Huttenlocher, Anna

    2014-04-24

    PSTPIP1 is a cytoskeletal adaptor and F-BAR protein that has been implicated in autoinflammatory disease, most notably in the PAPA syndrome: pyogenic sterile arthritis, pyoderma gangrenosum, and acne. However, the mechanism by which PSTPIP1 regulates the actin cytoskeleton and contributes to disease pathogenesis remains elusive. Here, we show that endogenous PSTPIP1 negatively regulates macrophage podosome organization and matrix degradation. We identify a novel PSTPIP1-R405C mutation in a patient presenting with aggressive pyoderma gangrenosum. Identification of this mutation reveals that PSTPIP1 regulates the balance of podosomes and filopodia in macrophages. The PSTPIP1-R405C mutation is in the SRC homology 3 (SH3) domain and impairs Wiskott-Aldrich syndrome protein (WASP) binding, but it does not affect interaction with protein-tyrosine phosphatase (PTP)-PEST. Accordingly, WASP inhibition reverses the elevated F-actin content, filopodia formation, and matrix degradation induced by PSTPIP1-R405C. Our results uncover a novel role for PSTPIP1 and WASP in orchestrating different types of actin-based protrusions. Our findings implicate the cytoskeletal regulatory functions of PSTPIP1 in the pathogenesis of pyoderma gangrenosum and suggest that the cytoskeleton is a rational target for therapeutic intervention in autoinflammatory disease.

  20. Intraoperative pulmonary hypertension occurred in an asymptomatic patient with pre-existent liver cirrhotic and portal hypertension

    PubMed Central

    Lu, Ling; Zhang, Feng; Li, Xiang-Cheng; Li, Guo-Qiang; Zhang, Chuan-Yong; Wang, Xue-Hao

    2008-01-01

    Portopulmonary hypertension (PPH) is clinically defined as the development of pulmonary arterial hypertension complicated by portal hypertension, with or without advanced hepatic disease. Physical signs may be absent in mild to moderate PPH and only appear in a hyperdynamic circulatory state. Similar signs of advanced liver disease can be observed in severe PPH, with ascites and lower extremity edema. Pulmonary hypertension is usually diagnosed after anesthetic induction during liver transplantation (LT). We present intraoperative pulmonary hypertension in a 41-year-old male patient with hepatic cirrhosis. Since this patient had no preoperation laboratory data supporting the diagnosises of pulmonary hypertension and was asymptomatic for a number of years, it was necessary to send him to the intensive care unit after operation. Further study should be focued on the diagnosis and treatment of pulmonary arterial hypertension in order to reduce its mortality. PMID:19084945

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

    DTIC Science & Technology

    2014-10-01

    propagation. Lgr5+ intestinal stem cells can initiate and maintain murine intestinal adenomas (6, 7). In mouse models of skin cancer, hair follicle bulge...initiated in Task 1 but further analysis will be collected in year 2 and a new approach will be added to Tasks 2 and 3 in year 2. Task 1. Test the in...vivo effects of castration on human luminal cancer subsets isolated from primary regenerated prostate tumors. Task 2. Test the in vivo growth

  2. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS EXCHANGE ESTABLISHMENT... eligibility and enrollment in the appropriate program without undue delay, based on the date the application... section. (b) Responsibilities related to individuals potentially eligible for Medicaid based on...

  3. Asymmetrical effects of adaptation to left- and right-shifting prisms depends on pre-existing attentional biases.

    PubMed

    Goedert, Kelly M; Leblanc, Andrew; Tsai, Sen-Wei; Barrett, Anna M

    2010-09-01

    Proposals that adaptation with left-shifting prisms induces neglect-like symptoms in normal individuals rely on a dissociation between the postadaptation performance of individuals trained with left- versus right-shifting prisms (e.g., Colent, Pisella, & Rossetti, 2000). A potential problem with this evidence is that normal young adults have an a priori leftward bias (e.g., Jewell & McCourt, 2000). In Experiment 1, we compared the line bisection performance of young adults to that of aged adults, who as a group may lack a leftward bias in line bisection. Participants trained with both left- and right-shifting prisms. Consistent with our hypothesis, while young adults demonstrated aftereffects for left, but not right prisms, aged adults demonstrated reliable aftereffects for both prisms. In Experiment 2, we recruited a larger sample of young adults, some of whom were right-biased at baseline. We observed an interaction between baseline bias and prism-shift, consistent with the results of Experiment 1: Left-biased individuals showed a reduced aftereffect when training with right-shifting prisms and right-biased individuals showed a reduced aftereffect when training with left-shifting prisms. These results suggest that previous failures to find generalizable aftereffects with right-shifting prisms may be driven by participants' baseline biases rather than specific effects of the prism itself.

  4. Combined direct regeneration protocols in tissue culture of different cumin genotypes based on pre-existing meristems.

    PubMed

    Ebrahimie, Esmaeil; Hosseinzadeh, Abdolhadi; Nagavi, Mohammad Reza; Ghannadha, Mohammad Reza; Mohammadie-Dehcheshmeh, Manijeh

    2007-05-01

    Rapid and genotype-independent protocols for two direct in vitro morphogenesis pathways including direct shoot organogenesis from embryo and direct shoot proliferation from node have been developed in cumin (Cuminum cyminum L.). Direct regenerations occurring without passing callus phase are important since fewer somaclonal variation and genotype-dependency are likely to arise from these methods in comparison with regenerations trough callus. After embryo culture, shoots with single-cellular origin were regenerated from the meristematic zone of embryo without any intermediate callus phase. In contrast, proliferated shoots with multi-cellular origin were directly regenerated from the axillary buds (meristems) of node explants. Effects of different concentrations of 6-Benzylaminopurine (BAP), alpha-Naphthaleneacetic Acid (NAA) and Indole-3-kcetic Acid (IAA) on B5 medium of embryo and node cultures as well as subculture were studied in detail. In direct organogenesis pathway from embryo explant, 0.1 mg L(-1) NAA + 1 mg L(-1) IAA resulted the highest shoot regeneration response (89.5 shoots per regenerated explant), whereas 0.1 mg L(-1) BAP + 1 mg L(-1) NAA was the most effective combination in direct shoot proliferation from node explant (42 shoots per regenerated explant). BAP (cytokinin) revealed the inhibitory effect on induction of direct shoot organogenesis pathway from embryo explant, while low concentration of BAP (0.1 mg L(-1)) had positive effect on direct shoot proliferation pathway from node explant. Subculturing was not necessary for shoot multiplication and elongation in embryo culture, whereas multiplication and elongation of shoots in node culture were associated to subculture on growth regulator-free medium. In other part of study, the behavior of different cumin genotypes in direct regeneration pathways was studied. Both direct organogenesis and direct proliferation pathways were applicable to different cumin genotypes and regenerated plants were phenotypically normal. This study supports the feasibility of combined direct regenerations protocols from embryo and node of cumin in germplasm conservation by in vitro cloning and genetic improvement programs.

  5. 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

    ... MINING POINT SOURCE CATEGORY BPT, BAT, BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Pt. 434, App... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the event that a pollutant concentration in the data used to determine baseline is lower than the daily...

  6. 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

    ... MINING POINT SOURCE CATEGORY BPT, BAT, BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Pt. 434, App... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the event that a pollutant concentration in the data used to determine baseline is lower than the daily...

  7. REVENUE-RAISING VS. OTHER APPROACHES TO ENVIRONMENTAL PROTECTION: THE CRITICAL SIGNIFICANCE OF PRE- EXISTING TAX DISTORTIONS. (R825313)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  8. Investigation of Cold Expansion of Short Edge Margin Holes with Pre-existing Cracks in 2024-T351 Aluminum Alloy

    DTIC Science & Technology

    2011-12-01

    INVESTIGATION OF COLD EXPANSION OF SHORT EDGE MARGIN HOLES WITH PREEXISTING CRACKS IN 2024-T351 ALUMINUM ALLOY by Dallen Lee...Aluminum Alloy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dallen Lee Andrew 5d. PROJECT NUMBER 5e. TASK NUMBER...SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 207 19a. NAME OF RESPONSIBLE PERSON a. REPORT

  9. Group invariant solution for a pre-existing fracture driven by a power-law fluid in permeable rock

    NASA Astrophysics Data System (ADS)

    Fareo, A. G.; Mason, D. P.

    2016-06-01

    Group invariant analytical and numerical solutions for the evolution of a two-dimensional fracture with nonzero initial length in permeable rock and driven by an incompressible non-Newtonian fluid of power-law rheology are obtained. The effect of fluid leak-off on the evolution of the power-law fluid fracture is investigated.

  10. INFECTIVITY OF CRYPTOSPORIDIUM PARVUM IN HEALTHY ADULTS WITH PRE-EXISTING ANTI-C. PARVUM SERUM IGG. (R824759)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  11. Pre-Existing Carbon Structure and Its Effect on Site-Specific Carbon Isotopes in Small Organic Molecules

    NASA Astrophysics Data System (ADS)

    Piasecki, A.; Eiler, J. M.

    2014-12-01

    The ability to measure site-specific isotopes in organic molecules allows for better understanding of the mechanisms of their biosynthetic and/or catagenic formation and destruction. Here we examine for site-specific isotopic composition of propane from natural and synthetic sources using novel instruments and techniques gas source mass spectrometry 1, and discuss the possible relationship of our findings to recent independent evidence from NMR measurements for the isotopic structures of long-chain alkanes2. A recent NMR study2 demonstrates that n-alkanes can be divided into three groups according to their site-specific carbon isotope structure: long (C16+) even carbon number, long (C17+) odd carbon number , and short (C11-C15). We modeled the isotopic site-specific composition of propane derived from these three distinct groups. If propane is cleaved from such long-chain hydrocarbons without fractionation, the long odd-numbered and the shorter alkanes would produce propane with an average terminal position 6-7‰ lighter than the center position, while the long even-numbered chain compounds would produce propane with a terminal position averaging around 7‰ heavier than the center. If, instead the fractionation associated with cleaving propane from such parent molecules is ~10‰ (as seems likely), then these average terminal — center differences should be decreased by ~5 ‰ (i.e., to -11-12 and +1-2 ‰, respectively). We will compare these predictions with our previous demonstrations of the changes in bulk and site specific compositions in propane due to isotope exchange equilibria, diffusion and conventional models of kerogen 'cracking', and will use these models as a framework for interpreting the observed site-specific isotopic compositions of propane from diverse natural gas deposits. 1. Piasecki, A. et al. Site-Specific Carbon Isotope Measurement of Organics by Gas Source Mass Spectrometry. Mineralogical Magazine 77, (2013). 2. Gilbert, A., Yamada, K. & Yoshida, N. Organic Geochemistry. Organic Geochemistry 62, 56-61 (2013).

  12. DNase I and proteinase K impair Listeria monocytogenes biofilm formation and induce dispersal of pre-existing biofilms.

    PubMed

    Nguyen, Uyen T; Burrows, Lori L

    2014-09-18

    Current sanitation methods in the food industry are not always sufficient for prevention or dispersal of Listeria monocytogenes biofilms. Here, we determined if prevention of adherence or dispersal of existing biofilms could occur if biofilm matrix components were disrupted enzymatically. Addition of DNase during biofilm formation reduced attachment (<50% of control) to polystyrene. Treatment of established 72h biofilms with 100μg/ml of DNase for 24h induced incomplete biofilm dispersal, with <25% biofilm remaining compared to control. In contrast, addition of proteinase K completely inhibited biofilm formation, and 72h biofilms-including those grown under stimulatory conditions-were completely dispersed with 100μg/ml proteinase K. Generally-regarded-as-safe proteases bromelain and papain were less effective dispersants than proteinase K. In a time course assay, complete dispersal of L. monocytogenes biofilms from both polystyrene and type 304H food-grade stainless steel occurred within 5min at proteinase K concentrations above 25μg/ml. These data confirm that both DNA and proteins are required for L. monocytogenes biofilm development and maintenance, and that these components of the biofilm matrix can be targeted for effective prevention and removal of biofilms.

  13. Do Pre-Existing Diabetes Social Support or Depressive Symptoms Influence the Effectiveness of a Diabetes Management Intervention?

    PubMed Central

    Rosland, Ann-Marie; Kieffer, Edith; Spencer, Michael; Sinco, Brandy; Palmisano, Gloria; Valerio, Melissa; Nicklett, Emily; Heisler, Michele

    2015-01-01

    Objective Examine influences of diabetes-specific social support (D-SS) and depressive symptoms on glycemic control over time, among adults randomized to a diabetes self-management education and support (DSME/S) intervention or usual care. Methods Data were from 108 African-American and Latino participants in a six-month intervention trial. Multivariable linear regression models assessed associations between baseline D-SS from family and friends and depressive symptoms with changes in HbA1c. We then examined whether baseline D-SS or depression moderated intervention-associated effects on HbA1c. Results Higher baseline D-SS was associated with larger improvements in HbA1c (adjusted ΔHbA1c -0.39% for each +1-point D-SS, p=0.02), independent of intervention-associated HbA1c decreases. Baseline depressive symptoms had no significant association with subsequent HbA1c change. Neither D-SS nor depression moderated intervention-associated effects on HbA1c. Conclusions and Practice Implications Diabetes self-management education and support programs have potential to improve glycemic control for participants starting with varying levels of social support and depressive symptoms. Participants starting with more support for diabetes management from family and friends improved HbA1c significantly more over six months than those with less support, independent of additional significant DSME/S intervention-associated HbA1c improvements. Social support from family and friends may improve glycemic control in ways additive to DSME/S. PMID:26234800

  14. PARTICLE GROWTH BY ACID-CATALYZED HETEROGENEOUS REACTIONS OF ORGANIC CARBONYLS ON PRE-EXISTING AEROSOLS. (R828176)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition.

    PubMed

    McCarthy, K; Velchik, M G; Alavi, A; Mandell, G A; Esterhai, J L; Goll, S

    1988-06-01

    Forty-six patients (23M, 23F) ranging in age from 19 to 79 yr with a clinical history of a nonunion fracture, surgery, diabetes or a soft-tissue infection were studied with [111In]oxine WBCs to detect osteomyelitis. There were 27 true-positive, nine true-negative, two false-positive and one false-negative. The false-positives and the false-negative occurred in patients with soft-tissue infections overlying the area of interest. All diagnoses were confirmed by intraoperative bone biopsies and cultures. Bone biopsy and scan were performed within 2 days of each other in 39 patients. The overall sensitivity was 97% (27/28), specificity, 82% (9/11) and the diagnostic accuracy, 92% (36/39). The remaining seven patients had negative [111In]WBC scans several months after positive bone biopsies and definite antibiotic treatment. This suggests that [In]WBC scans become negative after appropriate therapy is undertaken. Interobserver data was obtained from four nuclear physicians of varying experience blinded to clinical information. A high degree of agreement was found in over 90% of the cases. This study demonstrates the utility of [111In]WBC scans in the diagnosis and follow-up of complicated osteomyelitis and a high level of interobserver agreement in scan interpretation.

  16. Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.

    PubMed

    Ananth, Abhirami A; Tai, Lee-Hwa; Lansdell, Casey; Alkayyal, Almohanad A; Baxter, Katherine E; Angka, Leonard; Zhang, Jiqing; Tanese de Souza, Christiano; Stephenson, Kyle B; Parato, Kelley; Bramson, Jonathan L; Bell, John C; Lichty, Brian D; Auer, Rebecca C

    2016-01-01

    Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA)-dopachrome tautomerase (AdDCT) and resection resulting in major surgical stress (abdominal nephrectomy), we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B) in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC) population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients.

  17. Evaluating a parainfluenza virus 5-based vaccine in a host with pre-existing immunity against parainfluenza virus 5.

    PubMed

    Chen, Zhenhai; Xu, Pei; Salyards, Gregory W; Harvey, Stephen B; Rada, Balazs; Fu, Zhen F; He, Biao

    2012-01-01

    Parainfluenza virus 5 (PIV5), formerly known as simian virus 5 (SV5), is a paramyxovirus often referred to as canine parainfluenza virus (CPI) in the veterinary field. PIV5 is thought to be a contributing factor to kennel cough. Kennel cough vaccines containing live PIV5 have been used in dogs for many decades. PIV5 is not known to cause any diseases in humans or other animals. PIV5 has been used as a vector for vaccine development for humans and animals. One critical question concerning the use of PIV5 as a vector is whether prior exposure to PIV5 would prevent the use of PIV5-based vaccines. In this work, we have examined immunogenicity of a recombinant PIV5 expressing hemagglutinin (HA) of influenza A virus subtype 3 (rPIV5-H3) in dogs that were immunized against PIV5. We found that vaccination of the dogs containing neutralizing antibodies against PIV5 with rPIV5-H3 generated immunity against influenza A virus, indicting that PIV5-based vaccine is immunogenic in dogs with prior exposure. Furthermore, we have examined exposure of PIV5 in human populations. We have detected neutralizing antibody (nAb) against PIV5 in 13 out of 45 human serum samples (about 29 percent). The nAb titers in humans were lower than that in vaccinated dogs, suggesting that nAb in humans is unlikely to prevent PIV5 from being an efficacious vector in humans.

  18. Evaluating a Parainfluenza Virus 5-Based Vaccine in a Host with Pre-Existing Immunity against Parainfluenza Virus 5

    PubMed Central

    Chen, Zhenhai; Xu, Pei; Salyards, Gregory W.; Harvey, Stephen B.; Rada, Balazs; Fu, Zhen F.; He, Biao

    2012-01-01

    Parainfluenza virus 5 (PIV5), formerly known as simian virus 5 (SV5), is a paramyxovirus often referred to as canine parainfluenza virus (CPI) in the veterinary field. PIV5 is thought to be a contributing factor to kennel cough. Kennel cough vaccines containing live PIV5 have been used in dogs for many decades. PIV5 is not known to cause any diseases in humans or other animals. PIV5 has been used as a vector for vaccine development for humans and animals. One critical question concerning the use of PIV5 as a vector is whether prior exposure to PIV5 would prevent the use of PIV5-based vaccines. In this work, we have examined immunogenicity of a recombinant PIV5 expressing hemagglutinin (HA) of influenza A virus subtype 3 (rPIV5-H3) in dogs that were immunized against PIV5. We found that vaccination of the dogs containing neutralizing antibodies against PIV5 with rPIV5-H3 generated immunity against influenza A virus, indicting that PIV5-based vaccine is immunogenic in dogs with prior exposure. Furthermore, we have examined exposure of PIV5 in human populations. We have detected neutralizing antibody (nAb) against PIV5 in 13 out of 45 human serum samples (about 29 percent). The nAb titers in humans were lower than that in vaccinated dogs, suggesting that nAb in humans is unlikely to prevent PIV5 from being an efficacious vector in humans. PMID:23185558

  19. Cutaneous Manifestations of Multiple Myeloma.

    PubMed

    Behera, Binodini; Pattnaik, Monali; Sahu, Bharti; Mohanty, Prasenjeet; Jena, Swapna; Mohapatra, Liza

    2016-01-01

    Multiple myeloma (MM) is a proliferative disorder of plasma cells which produce abnormal immunoglobulin proteins. Skin involvement is rarely found in this disorder. They are either specific or nonspecific lesions. We report four such interesting patients who presented to us initially with common dermatoses such as leukocytoclastic vasculitis, pyoderma gangrenosum, and vesiculobullous disorders and were subsequently diagnosed to have MM. There were no skeletal involvements or renal function abnormality at the time of presentation. Unusual presentation, nonresponsiveness to conventional therapy, and abnormal blood parameters prompted us to suspect some underlying systemic conditions which were later confirmed to be MM after serum immunoelectrophoresis for M-band and bone marrow biopsy.

  20. Cutaneous Manifestations of Multiple Myeloma

    PubMed Central

    Behera, Binodini; Pattnaik, Monali; Sahu, Bharti; Mohanty, Prasenjeet; Jena, Swapna; Mohapatra, Liza

    2016-01-01

    Multiple myeloma (MM) is a proliferative disorder of plasma cells which produce abnormal immunoglobulin proteins. Skin involvement is rarely found in this disorder. They are either specific or nonspecific lesions. We report four such interesting patients who presented to us initially with common dermatoses such as leukocytoclastic vasculitis, pyoderma gangrenosum, and vesiculobullous disorders and were subsequently diagnosed to have MM. There were no skeletal involvements or renal function abnormality at the time of presentation. Unusual presentation, nonresponsiveness to conventional therapy, and abnormal blood parameters prompted us to suspect some underlying systemic conditions which were later confirmed to be MM after serum immunoelectrophoresis for M-band and bone marrow biopsy. PMID:27904188

  1. Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

    ClinicalTrials.gov

    2016-09-26

    Other Specified Inflammatory Disorders of Skin or Subcutaneous Tissue; Pyoderma Gangrenosum; Erosive Pustular Dermatosis of the Scalp; Sweet's Syndrome; Behcet's Disease; Bowel-associated Dermatosis-arthritis Syndrome; Pustular Psoriasis; Acute Generalized Exanthematous Pustulosis; Keratoderma Blenorrhagicum; Sneddon-Wilkinson Disease; IgA Pemphigus; Amicrobial Pustulosis of the Folds; Infantile Acropustulosis; Transient Neonatal Pustulosis; Neutrophilic Eccrine Hidradenitis; Rheumatoid Neutrophilic Dermatitis; Neutrophilic Urticaria; Still's Disease; Erythema Marginatum; Unclassified Periodic Fever Syndromes / Autoinflammatory Syndromes; Dermatitis Herpetiformis; Linear IgA Bullous Dermatosis; Bullous Systemic Lupus Erythematosus; Inflammatory Epidermolysis Bullosa Aquisita; Neutrophilic Dermatosis of the Dorsal Hands (Pustular Vasculitis); Small Vessel Vasculitis Including Urticarial Vasculitis; Erythema Elevatum Diutinum; Medium Vessel Vasculitis

  2. Autoinflammatory pustular neutrophilic diseases.

    PubMed

    Naik, Haley B; Cowen, Edward W

    2013-07-01

    This article provides a new categorization of inflammatory pustular dermatoses in the context of recent genetic and biological insights. Monogenic diseases with pustular phenotypes are discussed, including deficiency of interleukin 1 receptor antagonist, deficiency of the interleukin 36 receptor antagonist, CARD14-associated pustular psoriasis, and pyogenic arthritis, pyoderma gangrenosum, and acne. How these new genetic advancements may inform how previously described pustular diseases are viewed, including pustular psoriasis and its clinical variants, with a focus on historical classification by clinical phenotype, is also discussed.

  3. A common pathway in periodic fever syndromes.

    PubMed

    McDermott, Michael F

    2004-09-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease due to mutations in pyrin, which normally inhibits pro-interleukin-1beta (IL-1beta) cytokine processing to the active form. A novel role for pyrin has been proposed by Shoham et al., who studied patients with an autosomal dominant disease called pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. They demonstrated an interaction between pyrin and proline serine threonine phosphatase-interacting protein 1 (PSTPIP1), the protein involved in PAPA, and thus revealed a biochemical pathway common to both FMF and PAPA.

  4. Ecthyma gangrenosum in a patient with acute leukemia.

    PubMed

    Kryeziu, Emrush; Kryeziu, K; Bajraktari, Gjani; Abazi, M; Zylfiu, B; Rudhani, I; Sadiku, Sh; Ukimeri, A; Brovina, A; Dreshaj, Sh; Telaku, S

    2010-01-01

    Ecthymagangrenosum (EG)is a rare condition with characteristic clinical appearance of red maculae that progresses to a central area of necrosis surrounded by an erythematous halo. The most frequently it is caused by Pseudomonas bacteriaemia in neutropenic patient. The authors presents a patient with acute myloblastic leukemia M4 type in whom in relapse EG caused by Pseudomonas aeruginosa was found. The patient was treated with antibiotics and surgical debridement. The author wants to point out on clinical significance this condition with high mortality rate.

  5. New Described Dermatological Disorders

    PubMed Central

    Cevirgen Cemil, Bengu; Keseroglu, Havva Ozge; Kaya Akis, Havva

    2014-01-01

    Many advances in dermatology have been made in recent years. In the present review article, newly described disorders from the last six years are presented in detail. We divided these reports into different sections, including syndromes, autoinflammatory diseases, tumors, and unclassified disease. Syndromes included are “circumferential skin creases Kunze type” and “unusual type of pachyonychia congenita or a new syndrome”; autoinflammatory diseases include “chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome,” “pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome,” and “pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome”; tumors include “acquired reactive digital fibroma,” “onychocytic matricoma and onychocytic carcinoma,” “infundibulocystic nail bed squamous cell carcinoma,” and “acral histiocytic nodules”; unclassified disorders include “saurian papulosis,” “symmetrical acrokeratoderma,” “confetti-like macular atrophy,” and “skin spicules,” “erythema papulosa semicircularis recidivans.” PMID:25243162

  6. Proline-serine-threonine phosphatase interacting protein 1 inhibition of T-cell receptor signaling depends on its SH3 domain.

    PubMed

    Marcos, Tamara; Ruiz-Martín, Virginia; de la Puerta, María Luisa; Trinidad, Antonio G; Rodríguez, María del Carmen; de la Fuente, Miguel Angel; Sánchez Crespo, Mariano; Alonso, Andrés; Bayón, Yolanda

    2014-09-01

    Proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) is an adaptor protein associated with the cytoskeleton that is mainly expressed in hematopoietic cells. Mutations in PSTPIP1 cause the rare autoinflammatory disease called pyogenic arthritis, pyoderma gangrenosum, and acne. We carried out this study to further our knowledge on PSTPIP1 function in T cells, particularly in relation to the phosphatase lymphoid phosphatase (LYP), which is involved in several autoimmune diseases. LYP-PSTPIP1 binding occurs through the C-terminal homology domain of LYP and the F-BAR domain of PSTPIP1. PSTPIP1 inhibits T-cell activation upon T-cell receptor (TCR) and CD28 engagement, regardless of CD2 costimulation. This function of PSTPIP1 depends on the presence of an intact SH3 domain rather than on the F-BAR domain, indicating that ligands of the F-BAR domain, such as the PEST phosphatases LYP and PTP-PEST, are not critical for its negative regulatory role in TCR signaling. Additionally, PSTPIP1 mutations that cause the pyogenic arthritis, pyoderma gangrenosum and acne syndrome do not affect PSTPIP1 function in T-cell activation through the TCR.

  7. Topical therapy for drug-resistant pyoderma in small animals.

    PubMed

    Jeffers, James G

    2013-01-01

    The appearance and increasing prevalence of methicillin-resistant and multidrug-resistant staphylococcal skin infections has necessitated a change in how those infections are treated. Topical antibacterial treatments have evolved from elective adjunctive therapy to a more essential part of the treatment plan. This article reviews the ingredients and vehicles available for aggressive topical antibacterial treatment and prevention of Staphylococcus skin infections. Additionally, the basic tenets of improving client compliance and product efficacy are outlined.

  8. Inverse Compton scattering X-ray source yield optimization with a laser path folding system inserted in a pre-existent RF linac

    NASA Astrophysics Data System (ADS)

    Chaleil, A.; Le Flanchec, V.; Binet, A.; Nègre, J. P.; Devaux, J. F.; Jacob, V.; Millerioux, M.; Bayle, A.; Balleyguier, P.; Prazeres, R.

    2016-12-01

    An inverse Compton scattering source is under development at the ELSA linac of CEA, Bruyères-le-Châtel. Ultra-short X-ray pulses are produced by inverse Compton scattering of 30 ps-laser pulses by relativistic electron bunches. The source will be able to operate in single shot mode as well as in recurrent mode with 72.2 MHz pulse trains. Within this framework, an optical multipass system that multiplies the number of emitted X-ray photons in both regimes has been designed in 2014, then implemented and tested on ELSA facility in the course of 2015. The device is described from both geometrical and timing viewpoints. It is based on the idea of folding the laser optical path to pile-up laser pulses at the interaction point, thus increasing the interaction probability. The X-ray output gain measurements obtained using this system are presented and compared with calculated expectations.

  9. The significance of pre-existing, deeply weathered crystalline rock in interpreting the effects of glaciation in the Minnesota River valley, U.S.A.

    USGS Publications Warehouse

    Patterson, C.J.; Boerboom, Terrence

    1999-01-01

    Minnesota is largely underlain by Precambrian crystalline bedrock that was weathered to an average depth of 30 m prior to Late Cretaceous time. The fresh-rock-weathered-rock interface is irregular, with as much as 45 m of relief. Weathering exploited joints, locally isolating meter-sized volumes of rock known as corestones. Variable amounts of residuum were removed through glaciation to leave (1) saprolite overlain by an in-situ Late Cretaceous soil profile; (2) partially eroded saprolite; and (3) undulating fresh rock surfaces (commonly mantled by rounded boulders) that display striae and glacial or fluvial polish. Significant subglacial erosion of fresh bedrock is not required to form smoothly undulating bedrock surfaces with closed depressions; they may also form through removal of weathered bedrock and exposure of the weathering front. Large rounded boulders are not always shaped during transport; they may represent chemically rounded corestones resting at or near the bedrock source. Unambiguous evidence for glacial erosion includes striae and streamlining of bedrock parallel to striae. Polish on rock can be created fluvially, and smoothed grooves and ridges in the rock may be chemically produced. Many rounded boulders found in glacial till and strewn on bedrock surfaces probably originated as corestones.

  10. [Determining the parameters for receptor-ligand interaction by serial dilution method for the case when the ligand and receptor are in a pre-existing mixture].

    PubMed

    Bobrovnik, S A

    2005-01-01

    New methods of determining the binding parameters for ligand-receptor interaction are considered. The considered approaches are based on the earlier suggested method of serial dilution and application of so-called coordinates of dilution. It was shown that the suggested methods allow to evaluate affinity constant and ligand concentration even for the case, when the receptor and corresponding ligand of unknown concentration are in a mixture and their separation from each other is impossible. In this connection the suggested methods are especially useful for studying the ligand-receptor interaction if the receptor is very liable and its purification from the ligand would cause drastic changes of its binding properties.

  11. Impact of new traumatic or stressful life events on pre-existing PTSD in traumatized refugees: results of a longitudinal study

    PubMed Central

    Schock, Katrin; Böttche, Maria; Rosner, Rita; Wenk-Ansohn, Mechthild; Knaevelsrud, Christine

    2016-01-01

    Background A significant proportion of trauma survivors experience an additional critical life event in the aftermath. These renewed experiences of traumatic and stressful life events may lead to an increase in trauma-related mental health symptoms. Method In a longitudinal study, the effects of renewed experiences of a trauma or stressful life event were examined. For this purpose, refugees seeking asylum in Germany were assessed for posttraumatic stress symptoms (PTS), Posttraumatic Stress Diagnostic Scale (PDS), anxiety, and depression (Hopkins Symptom Checklist [HSCL-25]) before treatment start as well as after 6 and 12 months during treatment (N=46). Stressful life events and traumatic events were recorded monthly. If a new event happened, PDS and HSCL were additionally assessed directly afterwards. Mann–Whitney U-tests were performed to calculate the differences between the group that experienced an additional critical event (stressful vs. trauma) during treatment (n=23) and the group that did not (n=23), as well as differences within the critical event group between the stressful life event group (n=13) and the trauma group (n=10). Results Refugees improved significantly during the 12-month period of our study, but remained severely distressed. In a comparison of refugees with a new stressful life event or trauma, significant increases in PTS, anxiety, and depressive symptoms were found directly after the experience, compared to the group without a renewed event during the 12 months of treatment. With regard to the different critical life events (stressful vs. trauma), no significant differences were found regarding overall PTS, anxiety, and depression symptoms. Only avoidance symptoms increased significantly in the group experiencing a stressful life event. Conclusion Although all clinicians should be aware of possible PTS symptom reactivation, especially those working with refugees and asylum seekers, who often experience new critical life events, should understand symptom fluctuation and address it in treatment. Highlights of the article Within a longitudinal design, refugees currently in treatment are compared concerning symptom course after new traumatic or stressful events. New stressful life events and traumatic events increase posttraumatic, anxious, and depressive symptoms in the first 6 months after the events. Stressful and traumatic events overall did not show differential symptom exacerbations. Only avoidance symptoms were an exception; stressful life events were associated with an increase in PTS avoidance symptoms. Because reducing avoidance is the pivotal mechanism of psychotherapy with PTSD patients, clinicians should anticipate PTS symptom reactivation when patients are re-exposed to significant stressful stimuli, especially with asylum seekers and refugees, who often experience new stressful events. PMID:27834172

  12. Lentiviral vectors displaying modified measles virus gp overcome pre-existing immunity in in vivo-like transduction of human T and B cells.

    PubMed

    Lévy, Camille; Amirache, Fouzia; Costa, Caroline; Frecha, Cecilia; Muller, Claude P; Kweder, Hasan; Buckland, Robin; Cosset, François-Loïc; Verhoeyen, Els

    2012-09-01

    Gene transfer into quiescent T and B cells is important for gene therapy and immunotherapy approaches. Previously, we generated lentiviral vectors (LVs) pseudotyped with Edmonston (Ed) measles virus (MV) hemagglutinin (H) and fusion (F) glycoproteins (H/F-LVs), which allowed efficient transduction of quiescent human T and B cells. However, a major obstacle in the use of H/F-LVs in vivo is that most of the human population is vaccinated against measles. As the MV humoral immune response is exclusively directed against the H protein of MV, we mutated the two dominant epitopes in H, Noose, and NE. LVs pseudotyped with these mutant H-glycoproteins escaped inactivation by monoclonal antibodies (mAbs) but were still neutralized by human serum. Consequently, we took advantage of newly emerged MV-D genotypes that were less sensitive to MV vaccination due to a different glycosylation pattern. The mutation responsible was introduced into the H/F-LVs, already mutated for Noose and NE epitopes. We found that these mutant H/F-LVs could efficiently transduce quiescent lymphocytes in the presence of high concentrations of MV antibody-positive human serum. Finally, upon incubation with total blood, mimicking the in vivo situation, the mutant H/F-LVs escaped MV antibody neutralization, where the original H/F-LVs failed. Thus, these novel H/F-LVs offer perspectives for in vivo lymphocyte-based gene therapy and immunotherapy.

  13. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    PubMed Central

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2011-01-01

    Purpose A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. Results We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa – LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. Conclusions Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival. PMID:20592016

  14. Sugar homeostasis mediated by cell wall invertase GRAIN INCOMPLETE FILLING 1 (GIF1) plays a role in pre-existing and induced defence in rice.

    PubMed

    Sun, Li; Yang, Dong-lei; Kong, Yu; Chen, Ying; Li, Xiao-Zun; Zeng, Long-Jun; Li, Qun; Wang, Er-Tao; He, Zu-Hua

    2014-02-01

    Sugar metabolism and sugar signalling are not only critical for plant growth and development, but are also important for stress responses. However, how sugar homeostasis is involved in plant defence against pathogen attack in the model crop rice remains largely unknown. In this study, we observed that the grains of gif1, a loss-of-function mutant of the cell wall invertase gene GRAIN INCOMPLETE FILLING 1 (GIF1), were hypersusceptible to postharvest fungal pathogens, with decreased levels of sugars and a thinner glume cell wall in comparison with the wild-type. Interestingly, constitutive expression of GIF1 enhanced resistance to both the rice bacterial pathogen Xanthomonas oryzae pv. oryzae and the fungal pathogen Magnaporthe oryzae. The GIF1-overexpressing (GIF1-OE) plants accumulated higher levels of glucose, fructose and sucrose compared with the wild-type plants. More importantly, higher levels of callose were deposited in GIF1-OE plants during pathogen infection. Moreover, the cell wall was much thicker in the infection sites of the GIF1-OE plants when compared with the wild-type plants. We also found that defence-related genes were constitutively activated in the GIF1-OE plants. Taken together, our study reveals that sugar homeostasis mediated by GIF1 plays an important role in constitutive and induced physical and chemical defence.

  15. Magnetism as a distortion of a pre-existent primordial energy field and the possibility of extraction of electrical energy directly from space

    NASA Astrophysics Data System (ADS)

    Depalma, Bruce

    The spatial distortion induced into the homogeneous primordial energy field (PEF) by the anisotropy of the magnet is what is called magnetism. It is the thesis here that the distortion of the PEF occasioned by the magnet is the operative principle in the class of machinery known as induction machines. The PEF is also distorted as a consequence of the spatial reaction to the centripetal force field existing within the rotating magnetized conductor. Based on an effect first discovered by Michael Faraday in 1831, the N machine/space power generator is an electrical machine which has the possibility of producing electrical energy with significantly less mechanical power input than the presently used induction machines.

  16. Far-field pressurization likely caused one of the largest injection induced earthquakes by reactivating a large pre-existing basement fault structure

    USGS Publications Warehouse

    Yeck, William; Weingarten, Matthew; Benz, Harley M.; McNamara, Daniel E.; Bergman, E.; Herrmann, R.B; Rubinstein, Justin L.; Earle, Paul

    2016-01-01

    The Mw 5.1 Fairview, Oklahoma, earthquake on 13 February 2016 and its associated seismicity produced the largest moment release in the central and eastern United States since the 2011 Mw 5.7 Prague, Oklahoma, earthquake sequence and is one of the largest earthquakes potentially linked to wastewater injection. This energetic sequence has produced five earthquakes with Mw 4.4 or larger. Almost all of these earthquakes occur in Precambrian basement on a partially unmapped 14 km long fault. Regional injection into the Arbuckle Group increased approximately sevenfold in the 36 months prior to the start of the sequence (January 2015). We suggest far-field pressurization from clustered, high-rate wells greater than 12 km from this sequence induced these earthquakes. As compared to the Fairview sequence, seismicity is diffuse near high-rate wells, where pressure changes are expected to be largest. This points to the critical role that preexisting faults play in the occurrence of large induced earthquakes.

  17. Neutralizing antibody responses to foot-and-mouth disease quadrivalent (type O, A, C and Asia 1) vaccines in growing calves with pre-existing maternal antibodies.

    PubMed

    Patil, Prasanna K; Sajjanar, Channabasavaraj M; Natarajan, Chitattor; Bayry, Jagadeesh

    2014-03-14

    The presence of maternal antibodies is a major obstacle for eliciting protective immune responses to foot-and-mouth disease (FMD) vaccines in young, growing animals. In this report, we analyzed the ability of inactivated quadrivalent oil emulsified and aluminium hydroxide adjuvanted FMD vaccines to elicit neutralizing antibody responses in growing calves that had maternal antibodies. Our results demonstrate that oil emulsified vaccines but not aluminium hydroxide adjuvanted FMD vaccines could surmount maternal antibodies to elicit strong and significant levels of neutralizing antibody responses in growing claves.

  18. Metabolic, Cardiac and Renal Effects of the Slow Hydrogen Sulfide-Releasing Molecule GYY4137 During Resuscitated Septic Shock in Swine With Pre-Existing Coronary Artery Disease.

    PubMed

    Nubaum, Benedikt L; Vogt, Josef; Wachter, Ulrich; McCook, Oscar; Wepler, Martin; Matallo, José; Calzia, Enrico; Gröger, Michael; Georgieff, Michael; Wood, Mark E; Whiteman, Matthew; Radermacher, Peter; Hafner, Sebastian

    2017-01-19

    Decreased levels of endogenous hydrogen sulfide (H2S) contribute to atherosclerosis, whereas equivocal data are available on H2S effects during sepsis. Moreover, H2S improved glucose utilization in anaesthetized, ventilated, hypothermic mice, but normothermia and/or sepsis blunted this effect. The metabolic effects of H2S in large animals are controversial. Therefore, we investigated the effects of the H2S donor GYY4137 during resuscitated, fecal peritonitis-induced septic shock in swine with genetically and diet-induced coronary artery disease (CAD). 12 and 18 hours after peritonitis induction, pigs received either GYY4137 (10 mg kg, n = 9) or vehicle (n = 8). Before, at 12 and 24 hours of sepsis, we assessed left ventricular (pressure-conductance catheters) and renal (creatinine clearance, blood NGAL levels) function. Endogenous glucose production and glucose oxidation were derived from the plasma glucose isotope and the expiratory CO2/CO2 enrichment during continuous i.v. 1,2,3,4,5,6-C6-glucose infusion. GYY4137 significantly increased aerobic glucose oxidation, which coincided with higher requirements of exogenous glucose to maintain normoglycemia, as well as significantly lower arterial pH and decreased base excess. Apart from significantly lower cardiac eNOS expression and higher troponin levels, GYY4137 did not significantly influence cardiac and kidney function or the systemic inflammatory response. During resuscitated septic shock in swine with CAD, GYY4137 shifted metabolism to preferential carbohydrate utilization. Increased troponin levels are possibly due to reduced local NO availability. Cautious dosing, the timing of GYY4137 administration and interspecies differences most likely account for the absence of any previously described anti-inflammatory or organ-protective effects of GYY4137 in this model.

  19. SHORT-TERM INHALATION OF PARTICULATE TRANSITION METALS HAS LITTLE EFFECT ON THE ELECTROCARDIOGRAMS OF DOGS HAVING PRE-EXISTING CARDIAC ABNORMALITIES. (R826442)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  20. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.

  1. Slip preference on pre-existing faults: a guide tool for the separation of heterogeneous fault-slip data in extensional stress regimes

    NASA Astrophysics Data System (ADS)

    Tranos, Markos D.

    2012-05-01

    Synthetic fault-slip data have been considered in the present paper, in order to examine through a simple graphical manner the validity and use of the widely mentioned and applied criteria such as the slip preference, slip tendency, kinematic (P and T) axes, transport orientation and strain compatibility. The examination and description concern extensional stress regimes whose greatest principal stress axis (σ1) always remains in vertical position as in Andersonian stress states. In particular, radial extension (RE), radial-pure extension (RE-PE), pure extension (PE), pure extension-transtension (PE-TRN) and transtension (TRN) are examined with the aid of the Win-Tensor stress inversion software. In all of these extensional stress regimes only extensional faults can be activated. The lower dip angle of the reactivated faults is about 40° assuming that the coefficient of friction is no smaller than 0.6. The increase of the stress ratio and/or the fault dip angle up to 70° results in the increase of the slip deviation from the normal activation. Based on the present examination of the slip preference and slip tendency in different extensional stress regimes, a new simple and practical method is proposed herein in order to separate originally heterogeneous fault-slip data into homogeneous fault groups, by which different extensional stress regimes could be determined. The application of the method on the already published fault-slip data of Lemnos Island supports its validity since over 90% the resulted fault groups and stress regimes coincide to the already published ones.

  2. The role of pre-existing Precambrian structures and thermal anomaly in rift initiation and evolution-the Albertine and Rhino Grabens in Uganda

    NASA Astrophysics Data System (ADS)

    Katumwehe, Andrew Bushekwire

    We integrated Shuttle Radar Topography Mission Digital Elevation Models, airborne magnetic, radiometric, three-dimensional Full Tensor Gravity Gradiometry and Satellite gravity data to investigate the role of Precambrian structures in the evolution of the amagmatic Albertine-Rhino Grabens. The northern part of the Albertine-Rhino Graben extends within Mesoproterozoic Madi-Igisi fold belt wedged between two cratonic blocks. The southwestern part of the Albertine-Rhino Graben and the Edward-George Rift (EGR) extends within the Rwenzori and Kibara-Karagwe-Ankole orogenic belts. These extensional structures are separated by the ˜5 km high Rwenzori Mountains and represent the northern segment of the Western Branch of the East African Rift System. No expression of surface volcanic activities is observed within the Albertine-Rhino Graben except the Toro-Ankole (TAVF) volcanic fields that are found within the EGR. Our results suggest that: (1) Strain localization, strain transfer, rift segmentation as well as rift termination against the Aswa Shear Zone (ASZ) as due to the presence of different Precambrian structures. (2) The ASZ extent is ˜550 km in Uganda and South Sudan with a wider (˜50 km) deformation belt and its evolution was due to E-W to NE-SW oblique collision between East and West Gondwana with strain localized at the boundary between the Saharan Metacraton and the Northern Uganda Terrane. (3) Rift initiation in the Albertine-Rhino Graben is associated with a thermal structure that shows shallow CPD and high heat flow beneath the EGR and TAVF. We observed a localized thin crust beneath the Rwenzori Mountains, the western Albertine border fault, EGR and TAVF due to the removal of sub-continental lithospheric mantle as a result of delamination. The northward migration of the mantle fluids within lithospheric scale Madi-Igisi Fold and Thrust Belt facilitated strain localization during Albertine-Rhino rift initiation.

  3. Peritoneal delivery of sodium pyrophosphate blocks the progression of pre-existing vascular calcification in uremic apolipoprotein-E knockout mice.

    PubMed

    de Oliveira, Rodrigo B; Louvet, Loïc; Riser, Bruce L; Barreto, Fellype C; Benchitrit, Joyce; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Massy, Ziad A

    2015-08-01

    Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n = 18-19/group). Treatment was initiated 8 weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65 mg/kg or low dose, 0.33 mg/kg per day), oral sevelamer (3 % in diet), or placebo treatment for 8 weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16 weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

  4. Disease Interactions in a Shared Host Plant: Effects of Pre-Existing Viral Infection on Cucurbit Plant Defense Responses and Resistance to Bacterial Wilt Disease

    PubMed Central

    Mauck, Kerry E.; Pulido, Hannier; De Moraes, Consuelo M.; Stephenson, Andrew G.; Mescher, Mark C.

    2013-01-01

    Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana) contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila) at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV). We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA) in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host-plant quality for (and hence pathogen acquisition by) cucumber beetles. PMID:24155951

  5. Disease interactions in a shared host plant: effects of pre-existing viral infection on cucurbit plant defense responses and resistance to bacterial wilt disease.

    PubMed

    Shapiro, Lori R; Salvaudon, Lucie; Mauck, Kerry E; Pulido, Hannier; De Moraes, Consuelo M; Stephenson, Andrew G; Mescher, Mark C

    2013-01-01

    Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana) contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila) at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV). We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA) in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host-plant quality for (and hence pathogen acquisition by) cucumber beetles.

  6. Impact of promoting longer-lasting insecticide treatment of bed nets upon malaria transmission in a rural Tanzanian setting with pre-existing high coverage of untreated nets

    PubMed Central

    2010-01-01

    Background The communities of Namawala and Idete villages in southern Tanzania experienced extremely high malaria transmission in the 1990s. By 2001-03, following high usage rates (75% of all age groups) of untreated bed nets, a 4.2-fold reduction in malaria transmission intensity was achieved. Since 2006, a national-scale programme has promoted the use of longer-lasting insecticide treatment kits (consisting of an insecticide plus binder) co-packaged with all bed nets manufactured in the country. Methods The entomological inoculation rate (EIR) was estimated through monthly surveys in 72 houses randomly selected in each of the two villages. Mosquitoes were caught using CDC light traps placed beside occupied bed nets between January and December 2008 (n = 1,648 trap nights). Sub-samples of mosquitoes were taken from each trap to determine parity status, sporozoite infection and Anopheles gambiae complex sibling species identity. Results Compared with a historical mean EIR of ~1400 infectious bites/person/year (ib/p/y) in 1990-94; the 2008 estimate of 81 ib/p/y represents an 18-fold reduction for an unprotected person without a net. The combined impact of longer-lasting insecticide treatments as well as high bed net coverage was associated with a 4.6-fold reduction in EIR, on top of the impact from the use of untreated nets alone. The scale-up of bed nets and subsequent insecticidal treatment has reduced the density of the anthropophagic, endophagic primary vector species, Anopheles gambiae sensu stricto, by 79%. In contrast, the reduction in density of the zoophagic, exophagic sibling species Anopheles arabiensis was only 38%. Conclusion Insecticide treatment of nets reduced the intensity of malaria transmission in addition to that achieved by the untreated nets alone. Impacts were most pronounced against the highly anthropophagic, endophagic primary vector, leading to a shift in the sibling species composition of the A. gambiae complex. PMID:20579399

  7. HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

    PubMed Central

    Chayama, Kazuaki; Hayes, C. Nelson

    2015-01-01

    Sustained virological response (SVR) rates have increased dramatically following the approval of direct acting antiviral (DAA) therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs) may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV) therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens. PMID:26473914

  8. Septic complications involving hand and wrist in patients with pre-existing rheumatoid arthritis: The role of magnetic resonance imaging and sonography.

    PubMed

    Bortolotto, C; Gregoli, B; Coscia, D R; Draghi, F

    2012-06-01

    Sommario SCOPO DEL LAVORO: L'artrite settica (SA), che spesso coinvolge mano e polso, è comune nei pazienti con artrite reumatoide (AR) a causa dell'eziologia immunomediata della AR e dell'uso di farmaci immunosoppressivi. Le caratteristiche cliniche e di laboratorio possono non essere utili per distinguere tra recidiva di AR e sovrapposizione di SA. Il ruolo della risonanza magnetica (RM) è stata descritto in diversi studi. Il nostro obiettivo è quello di valutare il ruolo della ecografia (US). Materiali e Metodi. Negli ultimi 4 anni sono stati eseguiti 31 esami di risonanza magnetica della mano e del polso nel sospetto di SA come complicanza di AR. È stata utilizzata una risonanza magnetica da 1.5 T (Siemens Symphony, Erlangen, Germania) con protocollo standardizzato, che comprendeva la somministrazione di mezzo di contrasto; è stata eseguita anche un'ecografia con power Doppler utilizzando un ecografo Philips IU22. RISULTATI: Sono stati analizzati undici punti (secondo lo studio di Graif) per ogni esame di RM e di US. Alla RM il versamento articolare (37,5% di recidiva AR vs 100% sovrapposizioni di SA) e l'edema dei tessuti molli (25% vs 100%) erano indicativi di SA. Anche ecograficamente il versamento articolare (31.3% di AR recidiva 73,3% vs sovrapposizione di SA) e l'edema dei tessuti molli (12,5% vs 60%) erano indicativi di SA. CONCLUSIONE: I nostri risultati confermano che il versamento articolare e l'edema dei tessuti molli sono suggestivi per sovrapposizione di SA e che la RM è più sensibile nella loro valutazione. Anche se l'US è meno sensibile della RM, essa è importante nel guidare procedure invasive e nella valutazione dei pazienti che non possono essere sottoposti a RM.

  9. Effects of Pre-Existing Ice Crystals on Cirrus Clouds and Comparison between Different Ice Nucleation Parameterizations with the Community Atmosphere Model (CAM5)

    SciTech Connect

    Shi, Xiangjun; Liu, Xiaohong; Zhang, Kai

    2015-01-01

    In order to improve the treatment of ice nucleation in a more realistic manner in the Community Atmospheric Model version 5.3 (CAM5.3), the effects of preexisting ice crystals on ice nucleation in cirrus clouds are considered. In addition, by considering the in-cloud variability in ice saturation ratio, homogeneous nucleation takes place spatially only in a portion of cirrus cloud rather than in the whole area of cirrus cloud. With these improvements, the two unphysical limiters used in the representation of ice nucleation are removed. Compared to observations, the ice number concentrations and the probability distributions of ice number concentration are both improved with the updated treatment. The preexisting ice crystals significantly reduce ice number concentrations in cirrus clouds, especially at mid- to high latitudes in the upper troposphere (by a factor of ~10). Furthermore, the contribution of heterogeneous ice nucleation to cirrus ice crystal number increases considerably.Besides the default ice nucleation parameterization of Liu and Penner (2005, hereafter LP) in CAM5.3, two other ice nucleation parameterizations of Barahona and Nenes (2009, hereafter BN) and Kärcher et al. (2006, hereafter KL) are implemented in CAM5.3 for the comparison. In-cloud ice crystal number concentration, percentage contribution from heterogeneous ice nucleation to total ice crystal number, and preexisting ice effects simulated by the three ice nucleation parameterizations have similar patterns in the simulations with present-day aerosol emissions. However, the change (present-day minus pre-industrial times) in global annual mean column ice number concentration from the KL parameterization (3.24×106 m-2) is obviously less than that from the LP (8.46×106 m-2) and BN (5.62×106 m-2) parameterizations. As a result, experiment using the KL parameterization predicts a much smaller anthropogenic aerosol longwave indirect forcing (0.24 W m-2) than that using the LP (0.46 W m-2) and BN (0.39 W m-2) parameterizations.

  10. Important cutaneous manifestations of inflammatory bowel disease

    PubMed Central

    Trost, L; McDonnell, J

    2005-01-01

    Inflammatory bowel disease (IBD) has many extraintestinal manifestations. Cutaneous manifestations are usually related to the activity of the bowel disease but may have an independent course. Anyone presenting with IBD should be examined for cutaneous manifestations. Pyoderma gangrenosum is a severe painful ulcerating disease that requires moist wound management and, in the absence of secondary infection, systemic corticosteroids, cyclosporine, or both. Infliximab may also be used. Erythema nodosum is a common cause of tender red nodules of the shins. Management includes leg elevation, NSAIDs, and potassium iodide. Oral manifestations of IBD include aphthous stomatitis, mucosal nodularity (cobblestoning), and pyostomatitis vegetans. Treatment should be directed both at the cutaneous lesions and at the underlying systemic condition. PMID:16143688

  11. Three faces of recombination activating gene 1 (RAG1) mutations.

    PubMed

    Patiroglu, Turkan; Akar, Himmet Haluk; Van Der Burg, Mirjam

    2015-12-01

    Severe combined immune deficiency (SCID) is a group of genetic disorder associated with development of T- and/or B-lymphocytes. Recombination-activating genes (RAG1/2) play a critical role on VDJ recombination process that leads to the production of a broad T-cell receptor (TCR) and B-cell receptor (BCR) repertoire in the development of T and B cells. RAG1/2 genes mutations result in various forms of primary immunodeficiency, ranging from classic SCID to Omenn syndrome (OS) to atypical SCID with such as granuloma formation and autoimmunity. Herein, we reported 4 patients with RAG1 deficiency: classic SCID was seen in two patients who presented with recurrent pneumonia and chronic diarrhoea, and failure to thrive. OS was observed in one patient who presented with chronic diarrhoea, skin rash, recurrent lower respiratory infections, and atypical SCID was seen in one patient who presented with Pyoderma gangrenosum (PG) and had novel RAG1 mutation.

  12. Necrotizing dermatitis in patients receiving cancer chemotherapy.

    PubMed

    Dreizen, S; McCredie, K B; Bodey, G P; Keating, M J

    1987-03-01

    Necrotizing dermatitis in patients being treated with cancer chemotherapeutic agents can be of several types. Microbial causes can include a variety of bacteria and fungi, the most common being Pseudomonas aeruginosa. Gangrene from occlusive causes is not uncommon among cancer patients with coexisting atheromatous, thromboembolic, or obliterative vascular disease. Toxic gangrene is most commonly caused by extravasation of intravenously administered cytotoxic antineoplastic drugs but has also been associated with the use of coumarin congeners and the bite of the brown recluse spider. Pyoderma gangrenosum is an idiopathic condition that has been reported in association with myeloproliferative disorders. Finally, necrosis can be caused by the neoplasm itself, when its growth is so great that blood vessels are compressed and ischemia of the surrounding tissue results.

  13. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease*

    PubMed Central

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; de Freitas, Thaís Helena Proença; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  14. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-07-07

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness.

  15. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease.

    PubMed

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; Freitas, Thaís Helena Proença de; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity.

  16. Management of cutaneous disorders related to inflammatory bowel disease

    PubMed Central

    Pellicer, Zaira; Santiago, Jesus Manuel; Rodriguez, Alejandro; Alonso, Vicent; Antón, Rosario; Bosca, Marta Maia

    2012-01-01

    Almost one-third of patients with inflammatory bowel disease (IBD) develop skin lesions. Cutaneous disorders associated with IBD may be divided into 5 groups based on the nature of the association: specific manifestations (orofacial and metastatic IBD), reactive disorders (erythema nodosum, pyoderma gangrenosum, pyodermatitis-pyostomatitis vegetans, Sweet’s syndrome and cutaneous polyarteritis nodosa), miscellaneous (epidermolysis bullosa acquisita, bullous pemphigoid, linear IgA bullous disease, squamous cell carcinoma-Bowen’s disease, hidradenitis suppurativa, secondary amyloidosis and psoriasis), manifestations secondary to malnutrition and malabsorption (zinc, vitamins and iron deficiency), and manifestations secondary to drug therapy (salicylates, immunosupressors, biological agents, antibiotics and steroids). Treatment should be individualized and directed to treating the underlying IBD as well as the specific dermatologic condition. The aim of this review includes the description of clinical manifestations, course, work-up and, most importantly, management of these disorders, providing an assessment of the literature on the topic. PMID:24713996

  17. [Hereditary systemic autoinflammatory diseases. Part II: cryopyrin-associated periodic syndromes, pediatric systemic granulomatosis and PAPA syndrome].

    PubMed

    Aróstegui, Juan I; Yagüe, Jordi

    2008-03-29

    Hereditary systemic autoinflammatory diseases result from a genetically-based dysregulated inflammatory process, and are clinically characterized by recurrent or persistent systemic inflammatory episodes, which typically occur in the absence of infectious, neoplastic or autoimmune etiology. Elucidation of their molecular basis has enabled the use of genetic analyses to achieve an accurate and definitive diagnosis, and to establish a tailored treatment. The present review is the second and last part of an updated and comprehensive overview of hereditary systemic autoinflammatory diseases, and will introduce persistent, non-periodic autoinflammatory diseases, such as: a) the group of cryopyrin-associated periodic syndromes (CAPS), which includes familial cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and CINCA-NOMID syndrome; b) the group of pediatric systemic granulomatosis, which includes both Blau syndrome and early-onset sarcoidosis, and c) the pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.

  18. [Autoinflammatory syndrome].

    PubMed

    Ida, Hiroaki; Eguchi, Katsumi

    2009-03-01

    The autoinflammatory syndromes include a group of inherited diseases that are characterized by 1) seemingly unprovoked episodes of systemic inflammations, 2) absence of high titer of autoantibody or auto-reactive T cell, and 3) inborn error of innate immunity. In this article, we will focus on the clinical features, the pathogenesis related the genetic defects, and the therapeutic strategies in the representative disorders including familial Mediterranean fever (FMF), TNF receptor associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), hyper-IgD with periodic fever syndrome (HIDS), syndrome of pyogenic arthritis with pyoderma gangrenosum and acne (PAPA), and Blau syndrome. Recent advances in genetics and molecular biology have proceeded our understanding of the pathogenesis of autoinflammatory syndromes.

  19. PASS Syndrome: An IL-1-Driven Autoinflammatory Disease.

    PubMed

    Leuenberger, Mathieu; Berner, Jeanne; Di Lucca, Julie; Fischer, Lara; Kaparos, Nikolaos; Conrad, Curdin; Hohl, Daniel; So, Alexander; Gilliet, Michel

    2016-01-01

    PASS syndrome is a rare inflammatory disease characterized by a chronic-relapsing course of pyoderma gangrenosum, acne vulgaris, hidradenitis suppurativa and ankylosing spondylitis. Here, we describe a case of a patient with spontaneously recurrent purulent skin lesions along with seronegative spondylarthritis consistent with the PASS syndrome. During his disease exacerbation, the patient displayed episodes of fever along with elevated serum levels of interleukin (IL)-1β. Skin lesions were characterized by sterile neutrophilic infiltrates and showed a rapid response to the IL-1 receptor antagonist anakinra (Kineret®) consistent with the autoinflammatory nature of this disease. However, unlike other autoinflammatory diseases such as PAPA and PAPASH, we did not find mutations in the gene PSTPIP1, raising the possibility that other specific mutations in the IL-1 pathway may be involved.

  20. Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review.

    PubMed

    Smith, Elisabeth J; Allantaz, Florence; Bennett, Lynda; Zhang, Dongping; Gao, Xiaochong; Wood, Geryl; Kastner, Daniel L; Punaro, Marilynn; Aksentijevich, Ivona; Pascual, Virginia; Wise, Carol A

    2010-11-01

    PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an autosomal dominant, hereditary auto-inflammatory disease arising from mutations in the PSTPIP1/CD2BP1 gene on chromosome 15q. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in activation of the "inflammasome" involved in interleukin-1 (IL-1β) production. Overproduction of IL-1β is a clear molecular feature of PAPA syndrome. Ongoing research is implicating other biochemical pathways that may be relevant to the distinct pyogenic inflammation of the skin and joints characteristic of this disease. This review summarizes the recent and rapidly accumulating knowledge on these molecular aspects of PAPA syndrome and related disorders.

  1. [Autoinflammatory syndromes].

    PubMed

    Lamprecht, P; Gross, W L

    2009-06-01

    In its strict sense, the term "autoinflammatory syndromes" comprises the hereditary periodic fever syndromes (HPF), which are caused by mutations of pattern-recognition receptors (PRR) and perturbations of the cytokine balance. These include the crypyrinopathies, familial Mediterranean fever, TNF-receptor associated periodic fever syndrome (TRAPS), hyper-IgD and periodic syndrome (HIDS), pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, NALP12-HPF, and the Blau syndrome. The diseases are characterized by spontaneous activation of cells of the innate immunity in the absence of ligands. Autoantibodies are usually not found. HPF clinically present with recurrent fever episodes and inflammation, especially of serosal and synovial interfaces and the skin. Intriguingly, PRR-mediated autoinflammtory mechanisms also play a role in a number of chronic inflammatory and autoimmune diseases.

  2. Autoinflammatory syndromes.

    PubMed

    Galeazzi, M; Gasbarrini, G; Ghirardello, A; Grandemange, S; Hoffman, H M; Manna, R; Podswiadek, M; Punzi, L; Sebastiani, G D; Touitou, I; Doria, A

    2006-01-01

    The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells. These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation. Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial (Crohn's and Behçet's diseases) disorders. Mutations responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of inflammation and apoptosis.

  3. Acne-associated syndromes: models for better understanding of acne pathogenesis.

    PubMed

    Chen, W; Obermayer-Pietsch, B; Hong, J-B; Melnik, B C; Yamasaki, O; Dessinioti, C; Ju, Q; Liakou, A I; Al-Khuzaei, S; Katsambas, A; Ring, J; Zouboulis, C C

    2011-06-01

    Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

  4. Neutrophilic dermatoses in children.

    PubMed

    Berk, David R; Bayliss, Susan J

    2008-01-01

    The neutrophilic dermatoses are rare disorders, especially in children, and are characterized by neutrophilic infiltrates in the skin and less commonly in extracutaneous tissue. The neutrophilic dermatoses share similar clinical appearances and associated conditions, including inflammatory bowel disease, malignancies, and medications. Overlap forms of disease demonstrating features of multiple neutrophilic dermatoses may be seen. The manuscript attempts to provide an up-to-date review of (i) classical neutrophilic dermatoses, focusing on distinctive features in children and (ii) neutrophilic dermatoses which may largely be pediatric or genodermatosis-associated (Majeed, SAPHO [synovitis, severe acne, sterile palmoplantar pustulosis, hyperostosis, and osteitis] syndrome, PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), PFAPA (periodic fever with aphthous stomatitis, pharyngitis, and cervical adenopathy), and other periodic fever syndromes, and congenital erosive and vesicular dermatosis healing with reticulated supple scarring).

  5. Acne as a chronic systemic disease.

    PubMed

    Zouboulis, Christos C

    2014-01-01

    Acne is the most common skin disorder. In the majority of cases, acne is a disease that changes its skin distribution and severity over time; moreover, it can be a physically (scar development) and psychologically damaging condition that lasts for years. According to its clinical characteristics, it can be defined as a chronic disease according to the World Health Organization criteria. Acne is also a cardinal component of many systemic diseases or syndromes, such as congenital adrenal hyperplasia, seborrhea-acne-hirsutism-androgenetic alopecia syndrome, polycystic ovarian syndrome, hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, Apert syndrome, synovitis-acne-pustulosis-hyperostosis-osteitis syndrome, and pyogenic arthritis-pyoderma gangrenosum-acne syndrome. Recent studies on the Ache hunter gatherers of Paraguay detected the lack of acne in association with markedly lower rates of obesity, diabetes mellitus, hyperlipidemia, and cardiovascular diseases, a finding that indicates either a nutritional or a genetic background of this impressive concomitance.

  6. Diseases associated with hidranitis suppurativa: part 2 of a series on hidradenitis.

    PubMed

    Scheinfeld, Noah

    2013-06-15

    Hidradenitis suppurativa (HS), a pathologic follicular disease, impacts patients' lives profoundly and usually occurs in isolation. The diseases with the strongest association are obesity, depression, and pain. HS is associated with many diseases including acne conglobata (AC), dissecting cellulitis, pilonidal cysts, and obesity. Pyoderma fistulans sinifica (fox den disease) appears to be the same entity as Hurley Stage 2 of 3 HS. The rate of acne vulgaris in HS patients mirrors unaffected controls. The most common, albeit still uncommon, association is with seronegative, haplotype unlinked arthritis (most importantly B27), in particular spondolyarthritis. Crohn disease and HS occur together at a rate that varies from 0.6% to 38% in retrospective cases series. Ulcerative colitis occurred with HS in 14% of patients in one series. The next most common association is with pyoderma gangrenosum, but this association is likely under-reported. Synovitis-Acne-Pustulosis Hyperostosis-Osteitis (SAPHO) syndrome, which is rare, has more than 10 reports linking it to HS. Nine case reports have linked Dowling-Degos disease (DDD) to HS and two reports related HS to Fox-Fordyce disease (FF), but because both occur in the axilla this might be a mere coincidence. HS is rarely associated with ophthalmic pathology. Specifically, more than 5 reports link it to Keratitis-Ichthyosis-Deafness syndrome (KID); greater than10 cases link it to interstitial keratitis and 2 cases are linked to Behçet's disease. The presence of proteinuria and acute nephritis link HS to the kidney, especially since and reports have documented resolution of HS after renal transplant. Florid steatocystoma multiplex, Sjogren Syndrome, and HS have been linked and their reports likely underestimate their coincidence because all these entities involve occlusion (albeit by different mechanisms). Three reports link HS and amyloid, but both share some common genetic underpinnings and thus the coincidence of these

  7. The effect of pre-existing mental health comorbidities on the stage at diagnosis and timeliness of care of solid tumor malignances in a Veterans Affairs (VA) medical center.

    PubMed

    Wadia, Roxanne J; Yao, Xiaopan; Deng, Yanhong; Li, Jia; Maron, Steven; Connery, Donna; Gunduz-Bruce, Handan; Rose, Michal G

    2015-09-01

    There are limited data on the impact of mental health comorbidities (MHC) on stage at diagnosis and timeliness of cancer care. Axis I MHC affect approximately 30% of Veterans receiving care within the Veterans Affairs (VA) system. The purpose of this study was to compare stage at diagnosis and timeliness of care of solid tumor malignancies among Veterans with and without MHC. We performed a retrospective analysis of 408 charts of Veterans with colorectal, urothelial, and head/neck cancer diagnosed and treated at VA Connecticut Health Care System (VACHS) between 2008 and 2011. We collected demographic data, stage at diagnosis, medical and mental health co-morbidities, treatments received, key time intervals, and number of appointments missed. The study was powered to assess for stage migration of 15-20% from Stage I/II to Stage III/IV. There was no significant change in stage distribution for patients with and without MHC in the entire study group (p = 0.9442) and in each individual tumor type. There were no significant differences in the time intervals from onset of symptoms to initiation of treatment between patients with and without MHC (p = 0.1135, 0.2042 and 0.2352, respectively). We conclude that at VACHS, stage at diagnosis for patients with colorectal, urothelial and head and neck cancers did not differ significantly between patients with and without MHC. Patients with MHC did not experience significant delays in care. Our study indicates that in a medical system in which mental health is integrated into routine care, patients with Axis I MHC do not experience delays in cancer care.

  8. On the role of pre-existing, unhealed cracks on the bending strain response of Ag-clad (Bi,Pb){sub 2}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} tapes

    SciTech Connect

    Polak, M.; Parrell, J.A.; Polyanskii, A.A.; Pashitski, A.E.; Larbalestier, D.C.

    1997-02-01

    Studies of the transport critical current (I{sub c}), magnetization, magnetic flux penetration, and microstructure of pressed and rolled Ag-clad (Bi,Pb){sub 2}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} tapes (2223) have been made as a function of bending strain. Pressed tapes exhibited markedly less degradation of I{sub c} from strain than did rolled tapes, while the magnetization of pressed tapes declined much more rapidly with bending strain than did either of the transport currents. Magneto-optical imaging of nonbent pressed samples revealed a network of flux-penetrated defect channels that were primarily oriented parallel to the tape axis. Bending such samples to a small strain increased the visibility of these defects, believed to be cracks. This network correlates well to the cracks produced in intermediate thermomechanical processing deformation steps. The greater sensitivity of the transport current of rolled samples to bending is further direct proof of the fact that the tape {open_quotes}remembers{close_quotes} the cracks induced in the core during intermediate deformation and that heat treatment after the deformation does not heal all damage. {copyright} {ital 1997 American Institute of Physics.}

  9. The Impact of the Birth of a Child with Intellectual Disabilities on Pre-Existing Parental Christian Faith from the Perspective of Parents Who Have Parented Their Child to Adulthood

    ERIC Educational Resources Information Center

    Baines, Susannah; Hatton, Chris

    2015-01-01

    Background: Faith in the lives of UK families with an adult with intellectual disabilities is an under-researched area with little existing literature. Research in the United States with Christian parents suggests that they draw on their faith for coping (Rogers-Dulan 1998) and for understanding (Skinner et al. 1999). Methods: In this study,…

  10. Joint modelling of serological and hospitalization data reveals that high levels of pre-existing immunity and school holidays shaped the influenza A pandemic of 2009 in The Netherlands

    PubMed Central

    te Beest, Dennis E.; Birrell, Paul J; Wallinga, Jacco; De Angelis, Daniela; van Boven, Michiel

    2015-01-01

    Obtaining a quantitative understanding of the transmission dynamics of influenza A is important for predicting healthcare demand and assessing the likely impact of intervention measures. The pandemic of 2009 provides an ideal platform for developing integrative analyses as it has been studied intensively, and a wealth of data sources is available. Here, we analyse two complementary datasets in a disease transmission framework: cross-sectional serological surveys providing data on infection attack rates, and hospitalization data that convey information on the timing and duration of the pandemic. We estimate key epidemic determinants such as infection and hospitalization rates, and the impact of a school holiday. In contrast to previous approaches, our novel modelling of serological data with mixture distributions provides a probabilistic classification of individual samples (susceptible, immune and infected), propagating classification uncertainties to the transmission model and enabling serological classifications to be informed by hospitalization data. The analyses show that high levels of immunity among persons 20 years and older provide a consistent explanation of the skewed attack rates observed during the pandemic and yield precise estimates of the probability of hospitalization per infection (1–4 years: 0.00096 (95%CrI: 0.00078–0.0012); 5–19 years: 0.00036 (0.00031–0.0044); 20–64 years: 0.0015 (0.00091–0.0020); 65+ years: 0.0084 (0.0028–0.016)). The analyses suggest that in The Netherlands, the school holiday period reduced the number of infectious contacts between 5- and 9-year-old children substantially (estimated reduction: 54%; 95%CrI: 29–82%), thereby delaying the unfolding of the pandemic in The Netherlands by approximately a week. PMID:25540241

  11. Thermal-Mechanical Stress Analysis of PWR Pressure Vessel and Nozzles under Grid Load-Following Mode: Interim Report on the Effect of Cyclic Hardening Material Properties and Pre-existing Cracks on Stress Analysis Results

    SciTech Connect

    Mohanty, Subhasish; Soppet, William; Majumdar, Saurin; Natesan, Ken

    2016-03-15

    This report provides an update on an assessment of environmentally assisted fatigue for light water reactor components under extended service conditions. This report is a deliverable under the work package for environmentally assisted fatigue as part of DOE’s Light Water Reactor Sustainability Program. In a previous report (September 2015), we presented tensile and fatigue test data and related hardening material properties for 508 low-alloys steel base metal and other reactor metals. In this report, we present thermal-mechanical stress analysis of the reactor pressure vessel and its hot-leg and cold-leg nozzles based on estimated material properties. We also present results from thermal and thermal-mechanical stress analysis under reactor heat-up, cool-down, and grid load-following conditions. Analysis results are given with and without the presence of preexisting cracks in the reactor nozzles (axial or circumferential crack). In addition, results from validation stress analysis based on tensile and fatigue experiments are reported.

  12. Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease

    PubMed Central

    Culver, Emma L; Vermeulen, Ellen; Makuch, Mateusz; van Leeuwen, Astrid; Sadler, Ross; Cargill, Tamsin; Klenerman, Paul; Aalberse, Rob C; van Ham, S Marieke; Barnes, Eleanor; Rispens, Theo

    2015-01-01

    Background IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. Objectives To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental antigens. Methods Serum from 24 patients with IgG4-RD (14 treatment-naive, 10 treatment-experienced), 9 patients with primary sclerosing cholangitis and an elevated serum IgG4 (PSC-high IgG4), and 18 healthy controls were tested against egg white and yolk, milk, banana, cat, peanut, rice and wheat antigens by radioimmunoassay. Results We demonstrated an elevated polyclonal IgG4 response to multiple antigens in patients with IgG4-RD and in PSC-high IgG4, compared with healthy controls. There was a strong correlation between serum IgG4 and antigen-specific responses. Responses to antigens were higher in treatment-naive compared with treatment-experienced patients with IgG4-RD. Serum electrophoresis and immunofixation demonstrated polyclonality. Conclusions This is the first study to show enhanced levels of polyclonal IgG4 to multiple antigens in IgG4-RD. This supports that elevated IgG4 levels reflect an aberrant immunological regulation of the overall IgG4 response, but does not exclude that causality of disease could be antigen-driven. PMID:25646372

  13. Pre-existing cardiovascular conditions and high altitude travel. Consensus statement of the Medical Commission of the Union Internationale des Associations d'Alpinisme (UIAA MedCom) Travel Medicine and Infectious Disease.

    PubMed

    Donegani, Enrico; Hillebrandt, David; Windsor, Jeremy; Gieseler, Ulf; Rodway, George; Schöffl, Volker; Küpper, Thomas

    2014-01-01

    The number of persons visiting high altitude regions for various purposes (recreation, business etc.), and the age of people who do so, increases. Therefore there are more and more patients who need specific and individual advice to prevent emergency situations at altitude and to deal with emergencies if the safety strategy should fail. Since literature concerning cardiocirculatory diseases at altitude is scarce and studies with a controlled setting and high evidence level are missing, UIAA MedCom has checked all available literature for specific information to enable physicians who are active in travel or high altitude medicine to advise the patients at the highest possible level of evidence. It must be pointed out that there are several other medical fields where such information is mandatory, e.g. in occupational medicine, when employees depart to high altitude destinations for business purposes. The recommendations are based on a detailed literature research (databases, handbooks and the respective references). For easier use the paper has been structured as follows: general information, cardiocirculatory system and ECG at altitude, several cardiocirculatory diseases and their specific recommendations. The commission concludes, that a general "don't go!" is no state-of-the-art advice for the patients. With the information presented here a safe trip to altitude should be possible for many patients.

  14. Multidrug- and methicillin resistant Staphylococcus pseudintermedius as a cause of canine pyoderma: a case report.

    PubMed

    Vincze, Szilvia; Paasch, Angela; Walther, Birgit; Ruscher, Claudia; Lübke-Becker, Antina; Wieler, Lothar H; Barbara, Kohn

    2010-01-01

    A case of a dog with a long-term inflammatory skin disorder due to infection with methicillin-resistant Staphylococcus pseudintermedius (MRSP) is described. After initial diagnostics of MRSP, follow-up swabs of the dog (nose, skin) were taken twice after four and seven weeks. MRSP was constantly isolated from the skin and once from the nose. Since infected humans might be a source of reinfection, the owners of the dog were screened (nasal) three times during their pet's therapy. Thereby, the male owner was found to be colonized with MRSP once in the first sampling round. Comparative typing of all MRSP-isolates by pulsed-field gel electrophoresis (PFGE), SCCmec typing, multilocus sequence typing (MLST), spa typing, PCR-detection of the leukotoxin encoding operon (LukI) and the Staphylococcus intermedius-exfoliative toxin (SIET) as well as antimicrobial resistance profiling by broth microdilution revealed that all five MRSP isolates from the dog and the single isolate from the owner were indistinguishable by any of the applied methods. All isolates were assigned to a certain strain, a multidrug-resistant MRSP belonging to sequence type (ST) 71, spa type (t)05, harbouring SCCmecIII as well as the genes encoding LukI and SIET. In this case, a number of reasons might have contributed to therapy failure and re-infection, respectively (e. g. contact to other MRSP-colonized dogs, contact to MRSP-colonized humans, refusal to clip the dog's fur). In addition, MRSP-contaminated objects or surfaces in the household, which were difficult to disinfect or simply not considered as a potential source of MRSP, might have served as a source of re-infection. These results envision the possibility of a dog-to-human transmission of MRSP and the relevance of this aspect as a potential source of re-infection in cases of bacterial-supported long-term skin disorders in canine patients. First cases of MRSP infections in humans have been described only recently. However, the general pathogenic potential of multidrug resistant MRSP in humans is unknown so far and needs further investigation.

  15. Frequency and antimicrobial susceptibility of Staphylococcus species isolated from canine pyodermas.

    PubMed

    Medleau, L; Long, R E; Brown, J; Miller, W H

    1986-02-01

    Specimens obtained from pyogenic skin lesions of 210 dogs were culturally examined for staphylococci. A total of 215 isolates of staphylococci were biotyped, using the biochemical tests contained in a commercial staphylococcal identification system. Of 201 coagulase-positive isolates, 197 were identified as Staphylococcus intermedius, 3 as S aureus, and 1 as S hyicus. Of 14 coagulase-negative isolates, 5 were identified as S epidermidis, 5 as S xylosus, 3 as S simulans, and 1 as S hominis. Antimicrobial susceptibility tests were done on all staphylococcal isolates, using the standard disk-diffusion method. Staphylococcus intermedius isolates were susceptible to cephalothin, methicillin, and gentamicin. Resistance to ampicillin, penicillin G, and tetracycline was frequent. Antibiotic resistance was not associated with the depth of skin infection. Resistance to ampicillin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole was not associated with previous antibiotic use. Increased resistance to chloramphenicol, clindamycin, and erythromycin was associated with previous antibiotic therapy. Antimicrobial susceptibilities of the other Staphylococcus species isolated are reported, but the small numbers of these species precluded making meaningful comparison with S intermedius.

  16. Phenotypic and genotypic characterization of canine pyoderma isolates of Staphylococcus pseudintermedius for biofilm formation

    PubMed Central

    CASAGRANDE PROIETTI, Patrizia; STEFANETTI, Valentina; HYATT, Doreene Rose; MARENZONI, Maria Luisa; CAPOMACCIO, Stefano; COLETTI, Mauro; BIETTA, Annalisa; FRANCIOSINI, Maria Pia; PASSAMONTI, Fabrizio

    2015-01-01

    Biofilm-forming ability is increasingly being recognized as an important virulence factor in several Staphylococcus species. This study evaluated the biofilm-forming ability of sixty canine derived clinical isolates of S. pseudintermedius, using three phenotypic methods, microtiter plate test (MtP), Congo red agar method (CRA) and tube adherence test, and the presence and impact of biofilm-associated genes (icaA and icaD). The results showed that icaA and icaD genes were detected concomitantly in 55 (91.7%) of 60 isolates. A majority (88.3%) of the strains screened had matching results by the tube adherence test, MtP and PCR analysis. Better agreement (95%) was found between the PCR-based analysis and the CRA. Results of the icaA and icaD gene PCRs showed good agreement with CRA results, with a kappa of 0.7. Comparing the phenotypic methods, the statistical analysis showed that the agreement among the phenotypical tests using categorical data was generally good. Considering two classes (biofilm producer and biofilm non-producer), the percentage of matching results between the CRA method and the tube adherence test and between the CRA method and the MtP was 93.3%. A concordance of 100% was revealed between the MtP and the tube adherence test. The results indicate a high prevalence of the ica genes within S. pseudintermedius isolates, and their presence is associated with in vitro formation of a biofilm. A combination of phenotypic and genotypic tests is recommended for investigating biofilm formation in S. pseudintermedius. PMID:25892615

  17. Phenotypic and genotypic characterization of canine pyoderma isolates of Staphylococcus pseudintermedius for biofilm formation.

    PubMed

    Casagrande Proietti, Patrizia; Stefanetti, Valentina; Hyatt, Doreene Rose; Marenzoni, Maria Luisa; Capomaccio, Stefano; Coletti, Mauro; Bietta, Annalisa; Franciosini, Maria Pia; Passamonti, Fabrizio

    2015-08-01

    Biofilm-forming ability is increasingly being recognized as an important virulence factor in several Staphylococcus species. This study evaluated the biofilm-forming ability of sixty canine derived clinical isolates of S. pseudintermedius, using three phenotypic methods, microtiter plate test (MtP), Congo red agar method (CRA) and tube adherence test, and the presence and impact of biofilm-associated genes (icaA and icaD). The results showed that icaA and icaD genes were detected concomitantly in 55 (91.7%) of 60 isolates. A majority (88.3%) of the strains screened had matching results by the tube adherence test, MtP and PCR analysis. Better agreement (95%) was found between the PCR-based analysis and the CRA. Results of the icaA and icaD gene PCRs showed good agreement with CRA results, with a kappa of 0.7. Comparing the phenotypic methods, the statistical analysis showed that the agreement among the phenotypical tests using categorical data was generally good. Considering two classes (biofilm producer and biofilm non-producer), the percentage of matching results between the CRA method and the tube adherence test and between the CRA method and the MtP was 93.3%. A concordance of 100% was revealed between the MtP and the tube adherence test. The results indicate a high prevalence of the ica genes within S. pseudintermedius isolates, and their presence is associated with in vitro formation of a biofilm. A combination of phenotypic and genotypic tests is recommended for investigating biofilm formation in S. pseudintermedius.

  18. PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment.

    PubMed

    Cugno, Massimo; Borghi, Alessandro; Marzano, Angelo V

    2017-02-25

    Pyoderma gangrenosum (PG) is a neutrophilic dermatosis usually manifesting as skin ulcers with undermined erythematous-violaceous borders. It may be isolated, associated with systemic conditions or occurring in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis) or PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis). From a physiopathological point of view, all these conditions share common mechanisms consisting of over-activation of the innate immune system leading to increased production of the interleukin (IL)-1 family and 'sterile' neutrophil-rich cutaneous inflammation. From a genetic point of view, a number of mutations affecting the proteins of the inflammasome complex (the molecular platform responsible for triggering autoinflammation) or the proteins that regulate inflammasome function have been described in these disorders. As these debilitating entities are all associated with the over-expression of IL-1 and tumour necrosis factor (TNF)-α, biological drugs specifically targeting these cytokines are currently the most effective treatments but, given the emerging role of IL-17 in the pathogenesis of these syndromes, IL-17 antagonists may represent the future management of these conditions.

  19. [Diagnosis and Clinical Examination of Autoinflammatory Syndrome].

    PubMed

    Ida, Hiroaki

    2015-05-01

    Autoinflammatory syndrome is characterized by: 1) episodes of seemingly unprovoked inflammation, 2) the absence of a high titer of autoantibodies or auto-reactive T cells, and 3) an inborn error of innate immunity. In this decade, many autoinflammatory syndromes have been reported in Japan, and so many Japanese physicians have become aware of this syndrome. Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. The main monogenic autoinflammatory syndromes are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), cryopyrin-associated periodic syndrome (CAPS), Blau syndrome, and pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. We diagnosed these syndromes as clinical manifestations and performed genetic screening. Many serum cytokines are elevated in patients with autoinflammatory syndrome, but this is not disease-specific. The pathogeneses of many autoinflammatory syndromes are known to be related to inflammasomes, which are multiprotein complexes that serve as a platform for caspase 1 activation and interleukin-1β (IL-1β) and IL-18 muturation. Especially, NLRP3 inflammasomes may play a crucial role in the intiation and progression of FMF and CAPS. In the future, we hope to discover new clinical examinations which can provide evidence of inflammasome activation independent of genetic screening. In this issue, I introduce autoinflammatory syndromes and discuss the diagnosis and clinical examination of these syndromes.

  20. Biological therapy for dermatological manifestations of inflammatory bowel disease.

    PubMed

    Zippi, Maddalena; Pica, Roberta; De Nitto, Daniela; Paoluzi, Paolo

    2013-05-16

    Ulcerative colitis and Crohn's disease are the two forms of inflammatory bowel disease (IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions (immune-mediated extraintestinal manifestations), erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor (TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab (a fusion protein dimer of the human TNF-α receptor) and adalimumab (a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD (EN, PG and psoriasis).

  1. The endemic mimic: blastomycosis an illness often misdiagnosed.

    PubMed

    Bradsher, Robert W

    2014-01-01

    One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region.

  2. AUTOINFLAMMATORY PUSTULAR NEUTROPHILIC DISEASES

    PubMed Central

    Naik, Haley B.; Cowen, Edward W.

    2013-01-01

    SYNOPSIS The inflammatory pustular dermatoses constitute a spectrum of non-infectious conditions ranging from localized involvement to generalized disease with associated acute systemic inflammation and multi-organ involvement. Despite the variability in extent and severity of cutaneous presentation, each of these diseases is characterized by non-infectious neutrophilic intra-epidermal microabscesses. Many share systemic findings including fever, elevated inflammatory markers, inflammatory bowel disease and/or osteoarticular involvement, suggesting potential common pathogenic links (Figure 1). The recent discoveries of several genes responsible for heritable pustular diseases have revealed a distinct link between pustular skin disease and regulation of innate immunity. These genetic advances have led to a deeper exploration of common pathways in pustular skin disease and offer the potential for a new era of biologic therapy which targets these shared pathways. This chapter provides a new categorization of inflammatory pustular dermatoses in the context of recent genetic and biologic insights. We will discuss recently-described monogenic diseases with pustular phenotypes, including deficiency of IL-1 receptor antagonist (DIRA), deficiency of the IL-36 receptor antagonist (DITRA), CARD14-associated pustular psoriasis (CAMPS), and pyogenic arthritis, pyoderma gangrenosum, acne (PAPA). We will then discuss how these new genetic advancements may inform how we view previously described pustular diseases, including pustular psoriasis and its clinical variants, with a focus on historical classification by clinical phenotype. PMID:23827244

  3. [Atypical wounds: definition and classification].

    PubMed

    Situm, Mirna; Kolić, Maja

    2012-10-01

    Wound represents disruption of the anatomic and physiologic continuity of the skin. Regarding the healing process, wounds can be classified as acute or chronic wounds. A wound is considered chronic if healing does not occur within the expected period according to its etiology and localization. Chronic wounds can be classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic ulcers and two separate entities: diabetic foot and decubitus ulcers. Eighty percent of chronic wounds localized on the lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder is mostly neuropathic ulcer. Ninety-five percent of chronic wounds manifest as one of the above mentioned entities. Other forms of chronic wounds represent atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome).

  4. Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not a specific disease per se.

    PubMed

    Ball, Elizabeth; Newburger, Amy; Ackerman, A Bernard

    2003-08-01

    Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.

  5. Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

    PubMed Central

    Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

    2014-01-01

    Abstract The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

  6. Hidradenitis suppurrativa (acne inversa) as a systemic disease.

    PubMed

    Dessinioti, Clio; Katsambas, Andreas; Antoniou, Christina

    2014-01-01

    Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic follicular occlusive skin disorder characterized by recurrent abscesses, draining sinuses, and scarring, with a multifactorial pathogenesis. The answer to the question whether HS may be considered a systemic disease relies on the presence of accompanying systemic manifestations, on the proof of association with other diseases or conditions, and on the occurrence of systemic implications. We address these questions based on a systemic review of the existing literature. There are several reports in the literature of the coexistence of HS with other diseases, including pyoderma gangrenosum, PASH syndrome, Adamantiades-Behcet's disease, spondylarthropathy, Crohn's disease, SAPHO, pachyonychia congenita, Dowling-Degos disease, and the keratitis-ichthyosis-deafness (KID) syndrome. Case series exist only for Crohn's disease, while most other reports are anecdotal, thus, not providing high-quality scientific evidence. Based on well-designed studies, HS has been associated with the metabolic syndrome and with excess body weight or obesity. The link between HS and systemic associations may be attributed to common genetic or environmental factors or shared inflammatory pathways.

  7. Extraintestinal Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Schoepfer, Alain; Scharl, Michael; Lakatos, Peter L.; Navarini, Alexander; Rogler, Gerhard

    2015-01-01

    Abstract: Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD. PMID:26154136

  8. The inherited autoinflammatory syndrome: a decade of discovery.

    PubMed

    Goldfinger, Stephen

    2009-01-01

    The hereditary autoinflammatory diseases arise from mutations of genes regulating the innate immune system. These rare disorders are well characterized, both clinically and in terms of their molecular pathogenesis. The recurrent attacks of febrile polyserositis of Familial Mediterranean Fever (FMF) are due to defective pyrin, a protein that down-regulates inflammation. The Hyperimmunoglobulinemia D Syndrome (HIDS), which mimics FMF, results from a genetically conferred deficiency of mevalonate kinase. TRAPS (TNF Receptor Associated Periodic Syndrome), formerly known as Familial Hibernian Fever, is caused by a defective membrane receptor for TNF. Three other hereditary disorders which overlap in their clinical expression - Familial Cold Autoinflammatory Syndrome, the Muckle Wells syndrome, and Neonatal Onset Multisystem Inflamatory Disease (NOMID) - are a consequence of gain-of-function mutations of the gene encoding cryopyrin, the scaffolding protein of the inflammasome. The PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, Acne) results from mutations of a gene that increases the binding of its product (PSPSTPIP1) to pyrin, thereby blunting the inhibitory effect of pyrin on inflammasome activation.

  9. Pyrin Modulates the Intracellular Distribution of PSTPIP1.

    PubMed

    Waite, Andrea L; Schaner, Philip; Richards, Neil; Balci-Peynircioglu, Banu; Masters, Seth L; Brydges, Susannah D; Fox, Michelle; Hong, Arthur; Yilmaz, Engin; Kastner, Daniel L; Reinherz, Ellis L; Gumucio, Deborah L

    2009-07-07

    PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. Mutations in PSTPIP1 cause PAPA syndrome (Pyogenic sterile Arthritis, Pyoderma gangrenosum, and Acne), an autoinflammatory disease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial Mediterranean fever (FMF), a related autoinflammatory disorder. Since disease-associated mutations in PSTPIP1 enhance pyrin binding, PAPA syndrome and FMF are thought to share a common pathoetiology. The studies outlined here describe several new aspects of PSTPIP1 and pyrin biology. We document that PSTPIP1, which has homology to membrane-deforming BAR proteins, forms homodimers and generates membrane-associated filaments in native and transfected cells. An extended FCH (Fes-Cip4 homology) domain in PSTPIP1 is necessary and sufficient for its self-aggregation. We further show that the PSTPIP1 filament network is dependent upon an intact tubulin cytoskeleton and that the distribution of this network can be modulated by pyrin, indicating that this is a dynamic structure. Finally, we demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC, another pyrin binding protein. ASC specks are associated with inflammasome activity. PSTPIP1 molecules with PAPA-associated mutations are recruited by pyrin to ASC specks with particularly high efficiency, suggesting a unique mechanism underlying the robust inflammatory phenotype of PAPA syndrome.

  10. [Uncommon acne-associated syndromes and their significance in understanding the pathogenesis of acne].

    PubMed

    Hong, J-B; Prucha, H; Melnik, B; Ziai, M; Ring, J; Chen, W

    2013-04-01

    Acne is an intriguing model for the study of interactions between hormones, innate immunity, inflammation and wound healing (scarring). The manifestations and involvement of acne in different systemic diseases and some rare syndromes demonstrate its multifaceted nature. Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) and Pyogenic Arthritis-Pyoderma gangrenosum-Acne (PAPA) syndromes, both regarded as autoinflammatory diseases, highlight the attributes of inflammation in acne. While SAPHO syndrome can be used to explore the pathogenic role of Propionibacterium acnes in acne, PAPA syndrome and Apert syndrome can help understand the genetic influence on acne. The genetic defects in the gain-of-function of FGFR2 mutations in Apert syndrome and acne nevus of Munro lend further support to the hypothesis that the interaction of forkhead box class O (FoxOs)-mediated transcriptional regulation with androgen receptor transactivation and insulin/insulin like growth factor-1(IGF-1)-signaling is crucial in acne pathogenesis. Novel biologics, such as tumor necrosis factor (TNF) blockers and IL-1 inhibitors, appear promising in opposing the inflammation associated with SAPHO and PAPA syndromes, but it remains to seen if they can also improve severe acne particularly in the long term.

  11. Monogenic Auto-inflammatory Syndromes: A Review of the Literature.

    PubMed

    Azizi, Gholamreza; Khadem Azarian, Shahin; Nazeri, Sepideh; Mosayebian, Ali; Ghiasy, Saleh; Sadri, Ghazal; Mohebi, Ali; Khan Nazer, Nikoo Hossein; Afraei, Sanaz; Mirshafiey, Abbas

    2016-12-01

    Auto-inflammatory syndromes are a new group of distinct hereditable disorders characterized by episodes of seemingly unprovoked inflammation (most commonly in skin, joints, gut, and eye), the absence of a high titer of auto-antibodies or auto-reactive T cells, and an inborn error of innate immunity. A narrative literature review was carried out of studies related to auto-inflammatory syndromes to discuss the pathogenesis and clinical manifestation of these syndromes. This review showed that the main monogenic auto-inflammatory syndromes are familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). The data suggest that correct diagnosis and treatment of monogenic auto-inflammatory diseases relies on the physicians' awareness. Therefore, understanding of the underlying pathogenic mechanisms of auto-inflammatory syndromes, and especially the fact that these disorders are mediated by IL-1 secretion stimulated by monocytes and macrophages, facilitated significant progress in patient management.

  12. [Autoinflammatory diseases as cause of wound healing defects].

    PubMed

    Löhrer, R; Eming, R; Wolfrum, N; Krieg, T; Eming, S A

    2011-07-01

    Ulcerations of the skin and mucosal membranes are a common feature of autoinflammatory diseases. They can give raise to chronic wound healing defects and should be considered in the differential diagnosis of chronic skin ulcers. The increased activation of the innate immune system in the absence of an apparent provocation for inflammation is a hallmark of autoinflammatory diseases. Mutations and alterations of signaling pathways regulating the innate immune response to physical trauma/tissue damage result into an unrestrained activation of the inflammasome, which leads to increased activation of Interleukin-1. Uncontrolled recruitment and activation of myeloid effector cells within the wound site lead to the release of potent proteases that cause the degradation of structural components of the skin. The majority of these diseases respond well to immunosuppressive and immunomodulatory treatment regimes. Therapeutic resistance converts the acute inflammatory response into a chronic and non-resolving inflammatory process that leads to tissue degeneration. In this article we will focus on the review of those autoinflammatory diseases that often display ulcerative cutaneous and aphthous lesions including pyoderma gangrenosum, Behçet disease, PAPA syndrome and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). Furthermore, the article will be complemented by an overview of those inflammatory diseases that are associated with non-ulcerative cutaneous manifestations.

  13. [Autoinflammatory syndromes/fever syndromes].

    PubMed

    Schedel, J; Bach, B; Kümmerle-Deschner, J B; Kötter, I

    2011-05-01

    Hereditary periodic (fever) syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or joint symptoms. Some of these disorders present with organ involvement and serological signs of inflammation without fever. There is a strong serological inflammatory response with an elevation of serum amyloid A (SAA), resulting in an increased risk of secondary amyloidosis. There are monogenic disorders (familial mediterranean fever (FMF), hyper-IgD-syndrome (HIDS), cryopyrin-associated periodic syndromes (CAPS), "pyogenic arthritis, acne, pyoderma gangrenosum" (PAPA), and "pediatric granulomatous arthritis (PGA) where mutations in genes have been described, which in part by influencing the function of the inflammasome, in part by other means, lead to the induction of the production of IL-1β. In "early-onset of enterocolitis (IBD)", a functional IL-10 receptor is lacking. Therapeutically, above all, the IL-1 receptor antagonist anakinra is used. In case of TRAPS and PGA, TNF-antagonists (etanercept) may also be used; in FMF colchicine is first choice. As additional possible autoinflammatory syndromes, PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis and adenitis), Schnitzler syndrome, Still's disease of adult and pediatric onset, Behçet disease, gout, chronic recurrent multifocal osteomyelitis (CRMO) and Crohn's disease also are mentioned.

  14. Monogenic autoinflammatory diseases: concept and clinical manifestations.

    PubMed

    Almeida de Jesus, Adriana; Goldbach-Mansky, Raphaela

    2013-06-01

    The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency.

  15. Molecular and genetic characteristics of hereditary autoinflammatory diseases.

    PubMed

    Tunca, Mehmet; Ozdogan, Huri

    2005-02-01

    Autoinflammatory diseases are defined as recurrent "unprovoked" inflammatory events which do not produce high-titer autoantibodies or antigen-specific T cells. There are currently eight hereditary forms of these diseases: Familial Mediterranean fever (FMF), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), chronic infantile neurologic cutaneous articular (CINCA) syndrome or neonatal-onset multisystem inflammatory disease (NOMID), pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) and Blau syndrome. Apart from FMF (which has a prevalence of about 0.1 percent among non-Ashkenazi Jews, Armenians, Turks and Arabs), they are very rare disorders. FMF and HIDS are autosomal recessive diseases, all the other members of the family are autosomal and dominantly transmitted. Their common clinical features are recurrent and usually short attacks of synovitis and various skin eruptions; abdominal pain and fever are also frequently observed. The genes of all of these diseases have been discovered and, with the exception of HIDS, it was found that the proteins they encode share certain domains taking part in innate immunity and apoptosis. Thus it was evident that hereditary autoinflammatory diseases may help us understand better a number of important and prevalent pathologic events. We have reviewed the recent and rapidly accumulating knowledge on the molecular aspects of these disorders.

  16. Infevers: an evolving mutation database for auto-inflammatory syndromes.

    PubMed

    Touitou, Isabelle; Lesage, Suzanne; McDermott, Michael; Cuisset, Laurence; Hoffman, Hal; Dode, Catherine; Shoham, Nitza; Aganna, Ebun; Hugot, Jean-Pierre; Wise, Carol; Waterham, Hans; Pugnere, Denis; Demaille, Jacques; Sarrauste de Menthiere, Cyril

    2004-09-01

    The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.

  17. Skin manifestations in autoinflammatory syndromes.

    PubMed

    Braun-Falco, Markus; Ruzicka, Thomas

    2011-03-01

    Autoinflammatory diseases encompass a group of inflammatory diseases that are non-infectious, non-allergic, non-autoimmune and non-immunodeficient. The term was initially coined for a small group of familial periodic fever syndromes of which familial Mediterranean fever (FMF) is the most common and best known. Genetic and molecular analyses demonstrated for the majority of these diseases an impairment of inflammasomes to cause an increased activity of an interleukin-1-dependent inflammatory response. Over the last years an increasing number of either rare hereditary syndromes or acquired common diseases could be summarized under the designation of autoinflammatory disease, thus creating an emerging new rubric of inflammatory diseases. Many of them display cutaneous manifestations as both concomitant or more rarely main symptoms. To name some of them like erysipelas-like erythema in FMF; urticaria-like rashes in tumor necrosis factor receptor 1- or cryopyrin-associated periodic syndromes (TRAPS, CAPS), hyperimmunoglobulin D syndrome (HIDS) or Schnitzler syndrome; pyoderma gangrenosum and acne in PAPA syndrome; or behçetoid aphthous ulcerations in HIDS and PFAPA syndrome. Based on the new insights into pathogenesis one increasingly realizes the good response of these diseases to IL-1 antagonist therapies.

  18. Auto-inflammatory syndromes and oral health.

    PubMed

    Scully, C; Hodgson, T; Lachmann, H

    2008-11-01

    Auto-inflammatory diseases (periodic syndromes) are rare childhood-onset disorders which are characterized by fluctuating or recurrent episodes of fever and inflammation affecting serosal surfaces, joints, eyes and/or skin without significant autoantibody production or an identifiable underlying infection. They are disorders of innate immunity and the underlying genetic defect has been identified in most of the syndromes. Diagnosis relies on clinical symptoms and evidence of an elevated acute phase response during attacks, supported by finding mutations in the relevant genes. Several syndromes can lead to systemic AA amyloidosis. Aphthous-like oral ulceration has been reported as one manifestation in several of the syndromes, including periodic fever, aphthous-stomatitis, pharyngitis, adenitis (PFAPA) familial Mediterranean fever (FMF), hyperimmunoglobulinaemia D and periodic fever syndrome, tumour necrosis factor receptor associated periodic syndrome and pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA). Chronic jaw recurrent osteomyelitis has been recorded in chronic recurrent multifocal osteomyelitis. Advances in the molecular pathogenesis of these syndromes and the regulation of innate immunity have enhanced diagnosis, and rationalized therapies. This article reviews the periodic fever syndromes relevant to oral health and the suggested association of FMF with Behçet's disease.

  19. Identification of mesoderm development (mesd) candidate genes by comparative mapping and genome sequence analysis.

    PubMed

    Wines, M E; Lee, L; Katari, M S; Zhang, L; DeRossi, C; Shi, Y; Perkins, S; Feldman, M; McCombie, W R; Holdener, B C

    2001-02-15

    The proximal albino deletions identify several functional regions on mouse Chromosome 7 critical for differentiation of mesoderm (mesd), development of the hypothalamus neuroendocrine lineage (nelg), and function of the liver (hsdr1). Using comparative mapping and genomic sequence analysis, we have identified four novel genes and Il16 in the mesd deletion interval. Two of the novel genes, mesdc1 and mesdc2, are located within the mesd critical region defined by BAC transgenic rescue. We have investigated the fetal role of genes located outside the mesd critical region using BAC transgenic complementation of the mesd early embryonic lethality. Using human radiation hybrid mapping and BAC contig construction, we have identified a conserved region of human chromosome 15 homologous to the mesd, nelg, and hsdr1 functional regions. Three human diseases cosegregate with microsatellite markers used in construction of the human BAC/YAC physical map, including autosomal dominant nocturnal frontal lobe epilepsy (ENFL2; also known as ADNFLE), a syndrome of mental retardation, spasticity, and tapetoretinal degeneration (MRST); and a pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA).

  20. [Current therapeutic indications of thalidomide and lenalidomide].

    PubMed

    Ordi-Ros, Josep; Cosiglio, Francisco Javier

    2014-04-22

    Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Behçet syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. New thalidomide analogues have been developed but lack clinical experience. This paper is a review of the history, pharmacology, mechanism of action, clinical applications and side effects of thalidomide and its analogues.

  1. Rhinophyma-like hypertrophy of the nose caused by chronic facial pyoderma in a patient with Crohn's disease.

    PubMed

    Tsuchiya, Sunao; Ichioka, Shigeru; Tajima, Saori

    2014-10-01

    We present our experience with a 22-year-old man who had Crohn's disease with rhinophyma-like hypertrophy of the nose arising from pyogenic skin disease of the face. The clinical appearance did not precisely match any previously reported skin diseases.

  2. Identification of novel mutations in CD2BP1 gene in clinically proven rheumatoid arthritis patients of south India.

    PubMed

    Kumar, Bhattaram Siddhartha; Kumar, Pasupuleti Santhosh; Sowgandhi, Nannepaga; Prajwal, Bhattaram Manoj; Mohan, Alladi; Sarma, Kadainti Venkata Subbaraya; Sarma, Potukuchi Venkata Gurunadha Krishna

    2016-08-01

    Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA syndrome) is a rare autosomal dominant, auto-inflammatory disease that affects joints and skin. The disease results due to mutations in the cluster of differentiation 2 binding protein 1 (CD2BP1) gene on chromosome 15q24.3. Rheumatoid arthritis (RA) is a common, genetically complex disease that affects the joints with occasional skin manifestations. Studies related to the pathophysiology of inflammation in these two disorders show a certain degree of overlap at genetic level. The present study was done to confirm the existence of such a genetic overlap between PAPA syndrome and RA in south Indian population. In the present study 100 patients who were clinically diagnosed rheumatoid arthritis and 100 apparently healthy controls were chosen and the 15 exons of CD2BP1 gene were PCR-amplified and sequenced. The sequence analysis showed that in exon 3 thirty eight patients revealed presence of novel heterozygous missense mutations p.Glu51Asp, p.Leu57Arg and p.Ala64Thr. In exons 6, 10 and 14 eight patients showed 44 novel missense mutations and two patients showed novel frame shift mutations p.(Met123_Leu416delinsThr) and p.(Thr337Profs*52) leading to truncated protein formation. Such mutations were not seen in controls. Further, the in silico analysis revealed the mutant CD2BP1 structure showed deletion of Cdc15 and SH3 domains when superimposed with the wild type CD2BP1 structure with variable RMSD values. Therefore, these structural variations in CD2BP1 gene due to the mutations could be one of the strongest reasons to demonstrate the involvement of these gene variations in the patients with rheumatoid arthritis.

  3. JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases.

    PubMed

    Alves de Medeiros, Ana Karina; Speeckaert, Reinhart; Desmet, Eline; Van Gele, Mireille; De Schepper, Sofie; Lambert, Jo

    2016-01-01

    The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs.

  4. [Pathogenesis and Clinical Examination of Autoinflammatory Syndrome].

    PubMed

    Ida, Hiroaki

    2015-10-01

    Autoinflammatory syndrome is characterized by: 1) episodes of seemingly unprovoked inflammation, 2) the absence of a high titer of autoantibodies or auto-reactive T cells, and 3) an inborn error of innate immunity. In this decade, many autoinflammatory syndromes have been reported in Japan, and so many Japanese physicians have become aware of this syndrome. Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. The main monogenic autoinflammatory syndromes are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), cryopyrin-associated periodic syndrome (CAPS), Blau syndrome, and syndrome of pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). We diagnosed these syndromes as clinical manifestations and performed genetic screening. Many serum cytokines are elevated in patients with autoinflammatory syndrome, but this is not disease-specific. The pathogeneses of many autoinflammatory syndromes are known to be related to inflammasomes, which are multiprotein complexes that serve as a platform for caspase 1 activation and interleukin-1β(IL-1β) and IL-18 maturation. Especially, NLRP3 inflammasomes may play a crucial role in the initiation and progression of FMF and CAPS. Recently, it was reported that NETs (neutrophil extracellular traps) derived from neutrophils may also play an important role in the pathogenesis of FMF. In the future, we hope to discover new clinical examinations which can provide evidence of inflammasome activation independent of genetic screening. In this issue, I introduce autoinflammatory syndromes and discuss the pathogenesis and clinical examination of these syndromes.

  5. Medical Complications of Tattoos: A Comprehensive Review.

    PubMed

    Islam, Parvez S; Chang, Christopher; Selmi, Carlo; Generali, Elena; Huntley, Arthur; Teuber, Suzanne S; Gershwin, M Eric

    2016-04-01

    Tattoos are defined as the introduction of exogenous pigments into the dermis in order to produce a permanent design. This process may occur unintentional or may be deliberately administered for cosmetic or medical reasons. Tattoos have been around for over 5000 years and over time have evolved to represent a common cosmetic practice worldwide. Currently, adverse reactions are relatively rare and generally unpredictable and predominantly include immune-mediated reactions and skin infections. Along with better healthcare standards and more stringent public health mandates such as the provision of disposable needles, major infectious complications related to hepatitis and human retroviral infections have decreased significantly. When they do occur, skin infections are most frequently associated with Staphylococcus aureus or Streptococcus pyogenes. The aim of this study is to review the types and rates of medical complications of permanent tattoos. PubMed search and search dates were open ended. Acute local inflammation is the most common complication, but infections, allergic contact dermatitis, and other inflammatory or immune responses that are not well-characterized may occur. As many patients with immune reactions to tattoos do not react on skin or patch testing, it is postulated that the antigens contained in dyes or pigments are such small molecules that they need to be haptenized in order to become immunogenic. Red ink is associated more frequently with long-term reactions, including granulomatous and pseudolymphomatous phenomena or morphea-like lesions and vasculitis. Exacerbation of preexisting psoriasis, atopic dermatitis, and pyoderma gangrenosum may occur after tattooing. There is no well-defined association between cancer and tattoos. The treatment of tattoo-related complications may include local destructive measures (cryotherapy, electro-surgery, dermabrasion, chemical destruction, ablative laser destruction), surgical excision, and thermolysis of the

  6. Role of inflammatory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases

    PubMed Central

    Marzano, A V; Cugno, M; Trevisan, V; Fanoni, D; Venegoni, L; Berti, E; Crosti, C

    2010-01-01

    Pyoderma gangrenosum (PG) is a rare, immune-mediated inflammatory skin disease presenting with painful ulcers having undermined edges. Less commonly, bullous and vegetative variants exist. Histology consists of a neutrophil-rich dermal infiltrate. We characterized immunohistochemically the infiltrate in different variants of PG and in another neutrophilic dermatosis as Sweet's syndrome. We studied 21 patients with PG, eight with Sweet's syndrome and 20 controls, evaluating skin immunoreactivity for inflammatory cell markers (CD3, CD163 and myeloperoxidase), cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-8 and IL-17], metalloproteinases (MMP-2 and MMP-9) and vascular endothelial growth factor (VEGF). Immunoreactivities of CD3, CD163, myeloperoxidase, TNF-α, IL-8, IL-17, MMP-2, MMP-9 and VEGF were significantly higher in both PG and Sweet's syndrome than in controls (P = 0·0001). Myeloperoxidase (neutrophil marker), IL-8 (cytokine chemotactic for neutrophils) and MMP-9 (proteinase-mediating tissue damage) were expressed more significantly in both ulcerative and bullous PG than in vegetative PG as well as in Sweet's syndrome (P = 0·008–P = 0·0001). In ulcerative PG, the expression of CD3 (panT cell marker) and CD163 (macrophage marker) were significantly higher in wound edge than wound bed (P = 0·0001). In contrast, the neutrophil marker myeloperoxidase was expressed more significantly in wound bed than wound edge (P = 0·0001). Our study identifies PG as a paradigm of neutrophil-mediated inflammation, with proinflammatory cytokines/chemokines and MMPs acting as important effectors for the tissue damage, particularly in ulcerative and bullous PG where damage is stronger. In ulcerative PG, the wound bed is the site of neutrophil-recruitment, whereas in the wound edge activated T lymphocytes and macrophages pave the way to ulcer formation. PMID:20636397

  7. Crohn's-like complications in patients with ulcerative colitis after total proctocolectomy and ileal pouch-anal anastomosis.

    PubMed

    Goldstein, N S; Sanford, W W; Bodzin, J H

    1997-11-01

    Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become an established surgical procedure for ulcerative colitis. Occasional patients who have undergone IPAA develop persistent or recurrent episodes of pouchitis (chronic pouchitis), from which a subset also develop gastrointestinal and systemic complications that are identical to those seen in Crohn's disease. These complications include enteric stenoses or fistulas in the pouch or pouch inlet segment, perianal fistulas or abscesses, pouch fistulas, arthritis, iridocyclitis, and pyoderma gangrenosum. The development of Crohn's-like gastrointestinal complications in a patient with chronic pouchitis frequently engenders concern that the pathologist misinterpreted the proctocolectomy specimen as ulcerative colitis instead of Crohn's disease. We describe eight patients who developed chronic pouchitis and Crohn's-like complications after IPAA and total proctocolectomy. In each case, concern was voiced about misinterpretation of the proctocolectomy specimen as ulcerative colitis instead of Crohn's disease after the development of the Crohn's-like complications. Preoperatively, all eight patients had characteristic clinical, radiographic, and pathologic features of ulcerative colitis. Review of the pathology specimens indicated that all eight had ulcerative colitis. Crohn's-like complications are most likely related to chronic pouchitis, which probably is a form of recrudescent ulcerative colitis within the novel environment of the pouch. A diagnosis of Crohn's disease after IPAA surgery should only be made when reexamination of the original proctocolectomy specimen shows typical pathologic features of Crohn's disease, Crohn's disease arises in parts of the gastrointestinal tract distant from the pouch, pouch biopsies contain active enteritis with granulomas, or excised pouches show the characteristic features of Crohn's disease, including granulomas. There were no histologic differences in the total

  8. [A Case of Peristomal Cutaneous Ulcer Following Amebic Colitis Caused by Entamoeba histolytica].

    PubMed

    Sasaki, Yu; Yoshida, Tetsuya; Suzuki, Jun; Kobayashi, Seiki; Sato, Tomotaka

    2016-01-01

    A 66-year-old Japanese male with a history of a rectal ulcer and rectovesical fistula following brachytherapy and radiotherapy for prostate cancer, who had undergone colostomy and vesicotomy presented with a painful peristomal ulcer of approximately 5 x 2.5cm adjacent to the direction of 6 o'clock of the stoma in his left lower abdomen. Although he was admitted to be treated with intravenous antibiotics and topical debridement, the ulcer was rapidly increasing. In the laboratory findings, WBC was 12,400/μL, CRP was 16.9 mg/dL, ESR was 105mm in the first hour. Contrast enhanced CT images showed a wide high density area of skin and subcutaneous tissue around the stoma and dillitation of the transverse and descending colon. Colonoscopy showed furred profound ulcers in the rectum. A biopsy from the ulcer floor submitted to histopathology showed necrotic tissue with a mixed inflammatory infiltrates mainly composed of neutrophils and lymphocytes in the dermis. We suspected pyoderma gangrenosum with an inflammatory bowel disease in the beginning. Although he was started on oral prednisolone 60 mg daily, the ulcer did not respond to treatment. Additional methylprednisolone pulse therapy, intravenous cyclosporine and granulocytapheresis were also ineffective. A biopsy specimen from the skin ulcer margin showed erythrophagocytosis by trophozoites of amebae which were identified on PAS stained slides. The PCR method and stool examination showed positive for Entamoeba histolytica (E. histolytica), but serum antibodies were negative. Within two weeks of treatment with oral metronidazole 2,250 mg/day and topical metronidazole ointment, resolution of the ulcer was observed, then the prednisolone dosage was tapered. A split-thickness skin graft was used to cover the ulcer with a successful result. Even though we originally misdiagnosed this case, we finally reached a diagnosis of amebiasis. It is important to take account of amebiasis in the differential diagnosis of intractable

  9. JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases

    PubMed Central

    Alves de Medeiros, Ana Karina; Speeckaert, Reinhart; Desmet, Eline; Van Gele, Mireille; De Schepper, Sofie; Lambert, Jo

    2016-01-01

    The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs. PMID:27711196

  10. Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn’s Disease

    PubMed Central

    2013-01-01

    Background Cutaneous Crohn’s Disease is a notoriously difficult condition to treat and causes significant morbidity, impacting heavily on quality of life. This is the first study in adults examining the effect of topical tacrolimus on the different cutaneous manifestations of Crohn’s Disease. Methods This open label observational study of 20 patients with heterogeneous forms of cutaneous Crohn’s disease used topical tacrolimus 0.1% ointment once daily to affected areas for 12 weeks with a maximal total dose of 90g. Therapy was stopped at 12 weeks to assess whether the condition relapsed. Thereafter relapsing patients optionally continued an open label extension of topical tacrolimus therapy and were observed for a total of 12 months. Results Of seventeen patients completing the twelve-week study, fifteen improved using a specifically designed physicians’ global severity scale. One patient cleared, four showed a pronounced improvement (51-75%) and ten demonstrated a mild (1-25%) or moderate improvement (25-50%) in twelve weeks. Over twelve months eleven patients remained in the study, nine of which improved, one cleared and one showed no change. Perineal disease responded better with two out of twelve clearing, four showing pronounced benefit and four mild to moderate improvement. Long-term application of 0.1% tacrolimus applied to broken skin and mucosa was safe and serum levels of tacrolimus were undetectable in all subjects throughout the study. Conclusion 0.1% tacrolimus ointment was safe and effective in treating cutaneous manifestations of Crohn’s disease, particularly perineal disease and pyoderma gangrenosum, yet it seldom cleared the condition. Clinical trial registration ClinicalTrials.gov Protocol Registration System ID: 33000332 PMID:23331739

  11. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder.

    PubMed

    Wise, Carol A; Gillum, Joseph D; Seidman, Christine E; Lindor, Noralane M; Veile, Rose; Bashiardes, Stavros; Lovett, Michael

    2002-04-15

    PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne, OMIM #604416) and familial recurrent arthritis (FRA) are rare inherited disorders of early onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction. We recently localized the genes for PAPA syndrome and FRA to chromosome 15q and suggested that they are the same disorder. We have now established this by the identification of co-segregating disease-causing mutations in the CD2-binding protein 1 (CD2BP1; GenBank accession no XM 044569) gene in the two reported families with this disorder. E250Q or A230T amino acid substitutions occur within a domain highly homologous to yeast cleavage furrow-associated protein CDC15. CD2BP1 and its murine ortholog, proline-serine-threonine phosphatase interacting protein (PSTPIP1), are adaptor proteins known to interact with PEST-type protein tyrosine phosphatases (PTP). Yeast two-hybrid assays demonstrate severely reduced binding between PTP PEST and both the E250Q and A230T mutant proteins. Previous evidence supports the integral role of CD2BP1 and its interacting proteins in actin reorganization during cytoskeletal-mediated events. We hypothesize that the disease-causing mutations that we have identified compromise physiologic signaling necessary for the maintenance of proper inflammatory response. Accordingly we suggest classification of PAPA syndrome as an autoinflammatory disease. This CD2BP1-mediated biochemical pathway(s) may function in common inflammatory disorders with apparent etiological overlap, such as rheumatoid arthritis and inflammatory bowel disease.

  12. A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis.

    PubMed

    Ferguson, Polly J; Bing, Xinyu; Vasef, Mohammed A; Ochoa, Luis A; Mahgoub, Amar; Waldschmidt, Thomas J; Tygrett, Lorraine T; Schlueter, Annette J; El-Shanti, Hatem

    2006-01-01

    Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder that primarily affects bone but is often accompanied by inflammation of the skin and/or gastrointestinal tract. The etiology is unknown but evidence suggests a genetic component to disease susceptibility. Although most cases of CRMO are sporadic, there is an autosomal recessive syndromic form of the disease, called Majeed syndrome, which is due to homozygous mutations in LPIN2. In addition, there is a phenotypically similar mouse, called cmo (chronic multifocal osteomyelitis) in which the disease is inherited as an autosomal recessive disorder. The cmo locus has been mapped to murine chromosome 18. In this report, we describe phenotypic abnormalities in the cmo mouse that include bone, cartilage and skin inflammation. Utilizing a backcross breeding strategy, we refined the cmo locus to a 1.3 Mb region on murine chromosome 18. Within the refined region was the gene pstpip2, which shares significant sequence homology to the PSTPIP1. Mutations in PSTPIP1 have been shown to cause the autoinflammatory disorder PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne). Mutation analysis, utilizing direct sequencing, revealed a single base pair change c.293T --> C in the pstpip2 gene resulting in a highly conserved leucine at amino acid 98 being replaced by a proline (L98P). No other mutations were found in the coding sequence of the remaining genes in the refined interval, although a 50 kb gap remains unexplored. These data suggest that mutations in pstpip2 may be the genetic explanation for the autoinflammatory phenotype seen in the cmo mouse.

  13. PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders.

    PubMed

    Veillette, André; Rhee, Inmoo; Souza, Cleiton Martins; Davidson, Dominique

    2009-03-01

    The proline-, glutamic acid-, serine- and threonine-rich (PEST) family of protein tyrosine phosphatases (PTPs) includes proline-enriched phosphatase (PEP)/lymphoid tyrosine phosphatase (LYP), PTP-PEST, and PTP-hematopoietic stem cell fraction (HSCF). PEP/LYP is a potent inhibitor of T-cell activation, principally by suppressing the activity of Src family protein tyrosine kinases (PTKs). This function seems to be dependent, at least in part, on the ability of PEP to bind C-terminal Src kinase (Csk), a PTK also involved in inactivating Src kinases. Interestingly, a polymorphism of LYP in humans (R620W) is a significant risk factor for autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and lupus. The R620W mutation may be a 'gain-of-function' mutation. In non-hematopoietic cells, PTP-PEST is a critical regulator of adhesion and migration. This effect correlates with the aptitude of PTP-PEST to dephosphorylate cytoskeletal proteins such as Cas, focal adhesion associated-kinase (FAK), Pyk2, and PSTPIP. While not established, a similar function may also exist in immune cells. Additionally, overexpression studies provided an indication that PTP-PEST may be a negative regulator of lymphocyte activation. Interestingly, mutations in a PTP-PEST- and PTP-HSCF-interacting protein, PSTPIP1, were identified in humans with pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome and familial recurrent arthritis, two autoinflammatory diseases. These mutations abrogate the ability of PSTPIP1 to bind PTP-PEST and PTP-HSCF, suggesting that these two PTPs may be negative regulators of inflammation.

  14. Skin rash and arthritis a simplified appraisal of less common associations.

    PubMed

    Cozzi, A; Doria, A; Gisondi, P; Girolomoni, G

    2014-06-01

    Skin and joint manifestations are part of the clinical spectrum of many disorders. Well-known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low-specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo-papular, vesico-bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non-febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small-vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information.

  15. Interleukin-1, inflammasomes, autoinflammation and the skin.

    PubMed

    Contassot, Emmanuel; Beer, Hans-Dietmar; French, Lars E

    2012-05-31

    Interleukin 1, one of the first cytokines discovered in the 1980s, and a potent mediator of fever, pain and inflammation, is at present experiencing a revival in biology and medicine. Whereas the mechanism of activation and secretion of interleukin 1β, which critically regulates the function of this molecule, has remained mysterious for some 30 years following its discovery, the identification of a new cytoplasmic complex of proteins regulating IL-1β activation and secretion has carried our understanding of the role of IL1 in biology and disease one big step further. The inflammasomes, recently identified innate immune complexes that sense intracellular danger- (e.g. uric acid, ATP, cytoplasmic DNA) or pathogen-associated molecular patterns (e.g. muramyl dipeptide, flagellin, anthrax lethal toxin), are now known to be responsible for triggering inflammation in response to several molecular patterns, including, for example, uric acid, a danger-associated molecular pattern and trigger of gout. Dysregulation of inflammasome function is however also the cause of a family of genetic autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS) characterised by recurrent episodes of fever, urticarial-like skin lesions, systemic inflammation and arthritis. In mouse models recapitulating mutations observed in CAPS, neutrophilic inflammation of the skin is a cardinal feature, in a manner similar to several autoinflammatory diseases with skin involvement such as PAPA (pyoderma gangrenosum, acne and pyogenic arthritis) and Schnitzler's syndrome, in which IL-1β very probably plays a pathogenic role. In this article the role of the inflammasome in IL-1 biology, autoinflammation and disease is reviewed, together with new avenues for the therapy of these diseases.

  16. Neutrophilic Dermatoses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

    PubMed Central

    de Boysson, Hubert; Martin Silva, Nicolas; de Moreuil, Claire; Néel, Antoine; de Menthon, Mathilde; Meyer, Olivier; Launay, David; Pagnoux, Christian; Guillevin, Loïc; Puéchal, Xavier; Bienvenu, Boris; Aouba, Achille

    2016-01-01

    Abstract A few reports suggest combination of ANCA-associated vasculitis (AAV) and neutrophilic dermatoses (ND). We aimed to describe the main characteristics of patients presenting with both AAV and ND in a French cohort and through a systematic literature review, and to discuss the possible common pathogenic process involved. We conducted a retrospective study of patients with both conditions. Patients were selected via the French Internal Medicine Society (SNFMI) and the French Vasculitis Study Group (FVSG). A literature review focusing on a combination of both conditions, concentrated only on publications with well-established diagnoses and individual detailed data. Seventeen patients diagnosed with AAV and ND were identified in this cohort. Twelve patients had granulomatosis with polyangiitis (GPA), 4 had microscopic polyangiitis (MPA) and one had eosinophilic GPA (EGPA). Eight patients, all with GPA, displayed pyoderma gangrenosum (PG). Sweet's syndrome was observed in 6 patients (4 with MPA, one with GPA and one with EGPA) and erythema elevatum diutinum in the other three (2 with GPA and 1 with MPA). The literature review identified 33 additional patients with both conditions, including 26 with GPA. Altogether, of the 50 patients (17 from our study and 33 from the literature review), 33 (66%) patients presented with PG associated with GPA in 29 cases (89%). Corticosteroids were the first-line treatment in conjunction with an immunosuppressive agent in most cases. Outcomes were good and a total of 15 patients experienced a relapse. Patients who relapsed were more likely to have ear, nose and throat manifestation than patients who did not [12/15 (80%) relapsing patients vs. 15/35 (43%) non-relapsing patients; p = 0.03)]. In our stud, the most frequent association concerned GPA and PG. ND should be considered and specifically researched within the spectrum of cutaneous manifestations observed in AAV. PMID:26986103

  17. Certain Autoimmune Manifestations Are Associated With Distinctive Karyotypes and Outcomes in Patients With Myelodysplastic Syndrome

    PubMed Central

    Lee, Sang Jin; Park, Jin Kyun; Lee, Eun Young; Joo, Sang Hyun; Jung, Kyeong Cheon; Lee, Eun Bong; Song, Yeong Wook; Yoon, Sung-Soo

    2016-01-01

    Abstract Autoimmune manifestations (AIMs) are common in patients with myelodysplastic syndrome (MDS). This study aimed to investigate whether AIMs are associated with a specific cytogenetic abnormalities and worse survival in patients with MDS. A total of 67 MDS patients with AIMs and 134 age- and sex-matched MDS patients without AIMs, all of whom received medical care at Seoul National University Hospital from January 2000 through July 2014, were enrolled. The clinical features, chromosomal abnormalities, and outcomes were examined. The effect of AIMs on mortality was estimated after adjusting for age, sex, and the International Prognostic Scoring System. The mean age (±SD) at the time of MDS diagnosis was 54.5 ± 17.1 years, and 44.8% of patients were male. Neutrophilic dermatosis (ND; Sweet syndrome and pyoderma gangrenosum) was the most prevalent AIM (n = 24 36%]), followed by Behcet disease (10 [15%]), rheumatoid arthritis (9 [13%]), vasculitis (8 [12%]), myositis (3 [4%]), spondyloarthropathy (3 [4%]), and systemic lupus erythematous (2 [3%]). ND and vasculitis occurred at the time of MDS diagnosis, whereas other AIMs occurred years after MDS diagnosis. Deletion of 5q was associated with ND (P = 0.001), whereas trisomy 8 was associated with Behcet disease (P = 0.015). Strikingly, ND was associated with a 1.8-fold increase in mortality (95% CI 1.033–3.093; P = 0.038). Certain AIMs in MDS patients are associated with distinctive karyotypes and worse survival. A larger study is needed to confirm whether the presence of AIMs influences disease outcome in MDS. PMID:27043672

  18. Dissecting cellulitis (Perifolliculitis Capitis Abscedens et Suffodiens): a comprehensive review focusing on new treatments and findings of the last decade with commentary comparing the therapies and causes of dissecting cellulitis to hidradenitis suppurativa.

    PubMed

    Scheinfeld, Noah

    2014-05-16

    Dissecting cellulitis (DC) also referred to as to as perifolliculitis capitis abscedens et suffodiens (Hoffman) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. In the U.S., it predominantly occurs in African American men between 20-40 years of age. DC also occurs in other races and women more rarely. DC has been reported worldwide. Older therapies reported effective include: low dose oral zinc, isotretinoin, minocycline, sulfa drugs, tetracycline, prednisone, intralesional triamcinolone, incision and drainage, dapsone, antiandrogens (in women), topical clindamycin, topical isotretinoin, X-ray epilation and ablation, ablative C02 lasers, hair removal lasers (800nm and 694nm), and surgical excision. Newer treatments reported include tumor necrosis factor blockers (TNFB), quinolones, macrolide antibiotics, rifampin, alitretinoin, metronidazole, and high dose zinc sulphate (135-220 mg TID). Isotretinoin seems to provide the best chance at remission, but the number of reports is small, dosing schedules variable, and the long term follow up beyond a year is negligible; treatment failures have been reported. TNFB can succeed when isotretinoin fails, either as monotherapy, or as a bridge to aggressive surgical treatment, but long term data is lacking. Non-medical therapies noted in the last decade include: the 1064 nm laser, ALA-PDT, and modern external beam radiation therapy. Studies that span more than 1 year are lacking. Newer pathologic hair findings include: pigmented casts, black dots, and "3D" yellow dots. Newer associations include: keratitis-ichthyosis-deafness syndrome, Crohn disease and pyoderma gangrenosum. Older associations include arthritis and keratitis. DC is likely a reaction pattern, as is shown by its varied therapeutic successes and failures. The etiology of DC remains enigmatic and DC is distinct from hidradenitis suppurativa, which is shown by their varied responses to therapies and their

  19. The Relationship between NALP3 and Autoinflammatory Syndromes

    PubMed Central

    Campbell, Lorna; Raheem, Irfan; Malemud, Charles J.; Askari, Ali D.

    2016-01-01

    The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome, which is required for synthesis of interleukin-1β, has been implicated in the pathogenesis of several autoinflammatory syndromes. This review of the literature summarizes the interconnectedness of NALP3 inflammasome with some of these disorders. Familial Mediterranean fever results from a mutation in the Mediterranean fever (MEFV) gene, which encodes the pyrin protein. Previous study results suggest that pyrin suppresses caspase-1 activation, perhaps by competing for the adaptor protein, termed, pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ACS) which therefore interferes with NALP3 inflammasome activation. The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome is constitutively activated in cryopyrin-associated periodic syndromes due to gain-of-function mutations resulting from point mutations within the neuronal apoptosis inhibitor protein/class 2 transcription factor/heterokaryon incompatibility/telomerase-associated protein-1 (NACHT) domain of the NALP3 protein. Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is caused by mutations in the genes encoding proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). These PSTPIP1 mutants are thought to bind to pyrin causing an increase in the pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ASC) pyroptosome assembly leading to procaspase-1 recruitment and therefore its activation. Hyperimmunoglublinemia D syndrome is caused by mevalonate kinase (MVK) deficiency, which may be affected by protein accumulation that leads to NALP3 inflammasome activation. Tumor necrosis factor receptor–associated periodic syndrome is associated with mutations in the tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) gene which decreases the level of soluble tumor necrosis

  20. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.

    PubMed

    Shoham, Nitza G; Centola, Michael; Mansfield, Elizabeth; Hull, Keith M; Wood, Geryl; Wise, Carol A; Kastner, Daniel L

    2003-11-11

    Pyrin, the familial Mediterranean fever protein, is found in association with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis. These effects are mediated in part through cognate interactions with the adaptor protein ASC, which shares an N-terminal motif with pyrin. We sought additional upstream regulators of inflammation by using pyrin as the bait in yeast two-hybrid assays. We now show that proline serine threonine phosphatase-interacting protein [PSTPIP1, or CD2-binding protein 1 (CD2BP1)], a tyrosine-phosphorylated protein involved in cytoskeletal organization, also interacts with pyrin. Recently, PSTPIP1/CD2BP1 mutations were shown to cause the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA), a dominantly inherited autoinflammatory disorder mediated predominantly by granulocytes. Endogenous PSTPIP1/CD2BP1 and pyrin are coexpressed in monocytes and granulocytes and can be coimmunoprecipitated from THP-1 cells. The B box segment of pyrin was necessary and the B box/coiled-coil segment sufficient for this interaction, whereas the SH3 and coiled-coil domains of PSTPIP1/CD2BP1 were both necessary, but neither was sufficient, for pyrin binding. The Y344F PSTPIP1/CD2BP1 mutation, which blocks tyrosine phosphorylation, was associated with a marked reduction in pyrin binding in pervanadate-treated cells. PAPA-associated A230T and E250Q PSTPIP1/CD2BP1 mutations markedly increased pyrin binding as assayed by immunoprecipitation and, relative to WT, these mutants were hyperphosphorylated when coexpressed with c-Abl kinase. Consistent with the hypothesis that these mutations exert a dominant-negative effect on the previously reported activity of pyrin, we found increased IL-1beta production by peripheral blood leukocytes from a clinically active PAPA patient with the A230T PSTPIP1/CD2BP1 mutation and in cell lines transfected with both PAPA-associated mutants.

  1. The Relationship between NALP3 and Autoinflammatory Syndromes.

    PubMed

    Campbell, Lorna; Raheem, Irfan; Malemud, Charles J; Askari, Ali D

    2016-05-13

    The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome, which is required for synthesis of interleukin-1β, has been implicated in the pathogenesis of several autoinflammatory syndromes. This review of the literature summarizes the interconnectedness of NALP3 inflammasome with some of these disorders. Familial Mediterranean fever results from a mutation in the Mediterranean fever (MEFV) gene, which encodes the pyrin protein. Previous study results suggest that pyrin suppresses caspase-1 activation, perhaps by competing for the adaptor protein, termed, pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ACS) which therefore interferes with NALP3 inflammasome activation. The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 (NALP3) inflammasome is constitutively activated in cryopyrin-associated periodic syndromes due to gain-of-function mutations resulting from point mutations within the neuronal apoptosis inhibitor protein/class 2 transcription factor/heterokaryon incompatibility/telomerase-associated protein-1 (NACHT) domain of the NALP3 protein. Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is caused by mutations in the genes encoding proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1). These PSTPIP1 mutants are thought to bind to pyrin causing an increase in the pyrin domain of apoptosis/speck-like protein containing a caspase-recruitment domain (ASC) pyroptosome assembly leading to procaspase-1 recruitment and therefore its activation. Hyperimmunoglublinemia D syndrome is caused by mevalonate kinase (MVK) deficiency, which may be affected by protein accumulation that leads to NALP3 inflammasome activation. Tumor necrosis factor receptor-associated periodic syndrome is associated with mutations in the tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) gene which decreases the level of soluble tumor necrosis factor

  2. 21 CFR 524.1465 - Mupirocin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... daily. Treatment should not exceed 30 days. (2) Indications for use. For the topical treatment of bacterial infections of the skin, including superficial pyoderma, caused by susceptible strains...

  3. Targeted localized use of therapeutic antibodies: a review of non-systemic, topical and oral applications.

    PubMed

    Jones, Russell G A; Martino, Angela

    2016-01-01

    Therapeutic antibodies provide important tools in the "medicine chest" of today's clinician for the treatment of a range of disorders. Typically monoclonal or polyclonal antibodies are administered in large doses, either directly or indirectly into the circulation, via a systemic route which is well suited for disseminated ailments. Diseases confined within a specific localized tissue, however, may be treated more effectively and at reduced cost by a delivery system which targets directly the affected area. To explore the advantages of the local administration of antibodies, we reviewed current alternative, non-systemic delivery approaches which are in clinical use, being trialed or developed. These less conventional approaches comprise: (a) local injections, (b) topical and (c) peroral administration routes. Local delivery includes intra-ocular injections into the vitreal humor (i.e. Ranibizumab for age-related macular degeneration), subconjunctival injections (e.g. Bevacizumab for corneal neovascularization), intra-articular joint injections (i.e. anti-TNF alpha antibody for persistent inflammatory monoarthritis) and intratumoral or peritumoral injections (e.g. Ipilimumab for cancer). A range of other strategies, such as the local use of antibacterial antibodies, are also presented. Local injections of antibodies utilize doses which range from 1/10th to 1/100th of the required systemic dose therefore reducing both side-effects and treatment costs. In addition, any therapeutic antibody escaping from the local site of disease into the systemic circulation is immediately diluted within the large blood volume, further lowering the potential for unwanted effects. Needle-free topical application routes become an option when the condition is restricted locally to an external surface. The topical route may potentially be utilized in the form of eye drops for infections or corneal neovascularization or be applied to diseased skin for psoriasis, dermatitis, pyoderma

  4. Research on Skin Diseases - USSR -

    DTIC Science & Technology

    2007-11-02

    wide-spread a skin disease as eczema , is for the most part considered in class VIII, i.e. in the group of allergy <■■•■ disorders, together with...the group of pyodermas microbe eczemas and other eczema -like diseases, often recorded as strepto- or straphilodermia and treated as pyodermas, — we...put them in the eczema group. It is very probable that the great work being carried out in Leningrad in the fight against pyodermas in industrial

  5. A Real World, Observational Registry of Chronic Wounds and Ulcers

    ClinicalTrials.gov

    2016-05-18

    Diabetic Foot; Varicose Ulcer; Pressure Ulcer; Surgical Wound Dehiscence; Vasculitis; Skin Ulcer; Leg Ulcer; Wounds and Injuries; Pyoderma; Peripheral Arterial Disease; Diabetic Neuropathies; Lymphedema; Venous Insufficiency; Diabetes Complications; Amputation Stump

  6. 21 CFR 524.1465 - Mupirocin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... bacterial infections of the skin, including superficial pyoderma, caused by susceptible strains of Staphylococcus aureus and S. intermedius. (3) Limitations. Federal law restricts this drug to use by or on...

  7. 21 CFR 524.1465 - Mupirocin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... bacterial infections of the skin, including superficial pyoderma, caused by susceptible strains of Staphylococcus aureus and S. intermedius. (3) Limitations. Federal law restricts this drug to use by or on...

  8. 21 CFR 524.1465 - Mupirocin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... bacterial infections of the skin, including superficial pyoderma, caused by susceptible strains of Staphylococcus aureus and S. intermedius. (3) Limitations. Federal law restricts this drug to use by or on...

  9. 21 CFR 524.1465 - Mupirocin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... infections of the skin, including superficial pyoderma, caused by susceptible strains of Staphylococcus aureus and S. intermedius. (3) Limitations. Federal law restricts this drug to use by or on the order...

  10. A Regional Initiative to Reduce Skin Infections amongst Aboriginal Children Living in Remote Communities of the Northern Territory, Australia

    PubMed Central

    Andrews, Ross M.; Kearns, Therese; Connors, Christine; Parker, Colin; Carville, Kylie; Currie, Bart J.; Carapetis, Jonathan R.

    2009-01-01

    Background Linked to extreme rates of chronic heart and kidney disease, pyoderma is endemic amongst Aboriginal children in Australia's Northern Territory (NT). Many of those with pyoderma will also have scabies. We report the results of a community-based collaboration within the East Arnhem Region, which aimed to reduce the prevalence of both skin infections in Aboriginal children. Methodology/Principal Findings Commencing September 2004, we conducted an ecological study that included active surveillance for skin infections amongst children aged <15 years in five remote East Arnhem communities over a three year period. Screening was undertaken by trained local community workers, usually accompanied by another project team member, using a standard data collection form. Skin infections were diagnosed clinically with the aid of a pictorial flip chart developed for the purpose. Topical 5% permethrin was provided for age-eligible children and all household contacts whenever scabies was diagnosed, whilst those with pyoderma were referred to the clinic for treatment in accordance with current guidelines. In addition, annual mass scabies treatment (5% permethrin cream) was offered to all community residents in accordance with current guidelines but was not directly observed. Pyoderma and scabies prevalence per month was determined from 6038 skin assessments conducted on 2329 children. Pyoderma prevalence dropped from 46.7% at baseline to a median of 32.4% (IQR 28.9%–41.0%) during the follow-up period – an absolute reduction of 14.7% (IQR 4.7%–16.8%). Compared to the first 18 months of observation, there was an absolute reduction in pyoderma prevalence of 18 cases per 100 children (95%CI −21.0, −16.1, p≤0.001) over the last 18 months. Treatment uptake increased over the same period (absolute difference 13.4%, 95%CI 3.3, 23.6). While scabies prevalence was unchanged, the prevalence of infected scabies (that is with superimposed pyoderma) decreased from 3.7% (95

  11. Serum detection of IgG antibodies against Demodex canis by western blot in healthy dogs and dogs with juvenile generalized demodicosis.

    PubMed

    Ravera, Ivan; Ferreira, Diana; Gallego, Laia Solano; Bardagí, Mar; Ferrer, Lluís

    2015-08-01

    The aim of this study was to investigate the presence of canine immunoglobulins (Ig) G against Demodex proteins in the sera of healthy dogs and of dogs with juvenile generalized demodicosis (CanJGD) with or without secondary pyoderma. Demodex mites were collected from dogs with CanJGD. Protein concentration was measured and a western blot technique was performed. Pooled sera from healthy dogs reacted mainly with antigen bands ranging from 55 to 72 kDa. Pooled sera from dogs with CanJGD without secondary pyoderma reacted either with 10 kDa antigen band or 55 to 72 kDa bands. Pooled sera from dogs with CanJGD with secondary pyoderma reacted only with a 10 kDa antigen band. The results of this study suggest that both healthy dogs and dogs with CanJGD develop a humoral response against different proteins of Demodex canis.

  12. Predictive modeling of synergistic effects in nanoscale ion track formation

    DOE PAGES

    Zarkadoula, Eva; Pakarinen, Olli H.; Xue, Haizhou; ...

    2015-08-05

    Molecular dynamics techniques and the inelastic thermal spike model are used to study the coupled effects of inelastic energy loss due to 21 MeV Ni ion irradiation and pre-existing defects in SrTiO3. We determine the dependence on pre-existing defect concentration of nanoscale track formation occurring from the synergy between the inelastic energy loss and the pre-existing atomic defects. We show that the nanoscale ion tracks’ size can be controlled by the concentration of pre-existing disorder. This work identifies a major gap in fundamental understanding concerning the role played by defects in electronic energy dissipation and electron–lattice coupling.

  13. Antibiotic treatments of a methicillin-resistant Staphylococcus pseudintermedius infection in a dog: a case presentation.

    PubMed

    Decristophoris, P; Mauri, F; Albanese, F; Carnelli, A; Vanzetti, T; Zinsstag, J

    2011-09-01

    We report the antibiotic treatments administered to a female dog with mastitis and successive pyoderma. Microbiological investigations allowed the identification of Staphylococcus pseudintermedius after 54 days of various antibiotic treatments. The isolate carried the mecA gene and was resistant to 9 of 15 tested antibiotics. Consistent antibiotic treatment of the infection was possible only after accurate microbiological diagnosis.

  14. Biotypes of group A streptococci isolated from children.

    PubMed

    Kumar, M Palani; Menon, Thangam; Lobo, Charmaine; Anbumani, N; Kumar, C P Girish; Shanmugasundaram, S

    2004-03-01

    Thirty-eight isolates of group A streptococci from patients with pharyngitis, 13 isolates from patients with pyoderma and 28 carrier strains were subjected to biotyping by carbohydrate fermentation tests and production of beta-glucuronidase. Biotype 10 was observed most frequently among clinical isolates and biotypes 3 and 4 were most common among carrier isolates.

  15. Organic diseases mimicking acral lick dermatitis in six dogs.

    PubMed

    Denerolle, Philippe; White, Stephen D; Taylor, Tara S; Vandenabeele, Sophie I J

    2007-01-01

    Acral lick dermatitis ("lick granuloma") in dogs is often thought to have a behavioral etiology. However, other diseases may cause lesions on the distal legs, mimicking acral lick dermatitis. In this report, six dogs were presented with acral lick dermatitis-like lesions from different underlying causes-namely lymphoma, an orthopedic pin, deep pyoderma, mast cell tumor, leishmaniasis, and (presumptive) sporotrichosis.

  16. Regional distribution of ten common skin diseases in dogs.

    PubMed

    Sischo, W M; Ihrke, P J; Franti, C E

    1989-09-15

    We investigated the regional distributions of the most commonly diagnosed skin diseases in dogs from 17 North American veterinary teaching hospitals. Between January 1983 and December 1983, 11,456 diagnoses of skin disease were made. The 10 most common diagnoses were fleabite allergic dermatitis, skin cancer, pyoderma, seborrhea, allergy, demodectic acariasis (demodicosis), sarcoptic acariasis, immune-mediated skin disease, endocrine related skin disease, and acral lick dermatitis. Regional differences in the frequency of skin diseases were apparent. The northeast region had high frequencies of fleabite allergic dermatitis, allergy, and immune-mediated disease, and a low frequency of seborrhea. The midwest had a high frequency of seborrhea, and low frequencies of demodectic acariasis and allergy. In the plains region, low frequencies of fleabite allergic dermatitis, pyoderma, seborrhea, allergy, and demodectic acariasis were detected. In the west, the frequencies of fleabite allergic dermatitis, skin cancer, pyoderma, seborrhea, and acral lick dermatitis were high, whereas few dogs had allergic disease and sarcoptic acariasis. The southwest had high frequencies of fleabite allergic dermatitis and demodectic and sarcoptic acariasis. Fleabite allergic dermatitis, pyoderma, and demodectic and sarcoptic acariasis were frequently diagnosed in the southeast, but the number of dogs with seborrhea was low.

  17. Sudden Appearance of Indurated Erythematous Plaques on a Man's Face

    PubMed Central

    Carter, A.; Shulman, K.

    2016-01-01

    Rosacea fulminans (RF), previously known as pyoderma faciale, is a rare presentation of rosacea mostly seen in young women. RF is seen very rarely in men. We present below a case of a fifty-year-old male who presented with RF and was successfully treated with a combination of corticosteroids and isotretinoin. PMID:27703816

  18. 12 CFR 334.20 - Coverage and definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FAIR CREDIT REPORTING Affiliate Marketing § 334.20 Coverage and definitions. (a) Coverage. Subpart C of... account numbers, names, or addresses. (4) Pre-existing business relationship. (i) In general. The term “pre-existing business relationship” means a relationship between a person, or a person's...

  19. 12 CFR 571.20 - Coverage and definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... information” means any information the communication of which would be a consumer report if the exclusions... mortgage lender sells the consumer's entire loan to an investor, the mortgage lender has a pre-existing... sells the loan, and the investor has a pre-existing business relationship with the consumer...

  20. Settling No Conflict in the Public Place: Truth in Education, and in Rancierean Scholarship

    ERIC Educational Resources Information Center

    Bingham, Charles

    2010-01-01

    This essay offers an educational understanding of truth deriving from the work of Jacques Ranciere. Unlike other educational accounts--the traditional, progressive, and critical accounts--of truth that take education as a way of approaching pre-existing truths (or lack of pre-existing truths), this essay establishes an account of truth that is…

  1. 45 CFR 152.14 - Eligibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS PRE-EXISTING CONDITION... an individuals' identified pre-existing condition. (3) Medical or health condition. Documented evidence of the existence or history of certain medical or health condition, as approved or specified...

  2. 12 CFR 222.21 - Affiliate marketing opt-out and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... depository institution does not have a pre-existing business relationship with the consumer and none of the...) By an affiliate that has or has previously had a pre-existing business relationship with the consumer... business relationship with the consumer. (b) Making solicitations—(1) In general. For purposes of...

  3. 12 CFR 334.21 - Affiliate marketing opt-out and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... depository institution does not have a pre-existing business relationship with the consumer and none of the...) By an affiliate that has or has previously had a pre-existing business relationship with the consumer... business relationship with the consumer. (b) Making solicitations—(1) In general. For purposes of...

  4. 12 CFR 571.21 - Affiliate marketing opt-out and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... institution does not have a pre-existing business relationship with the consumer and none of the other... affiliate that has or has previously had a pre-existing business relationship with the consumer; or (ii) As... relationship with the consumer. (b) Making solicitations—(1) In general. For purposes of this subpart, you...

  5. 16 CFR 680.21 - Affiliate marketing opt-out and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... has a relationship with the creditor's securities affiliate for management of the consumer's.... The creditor does not have a pre-existing business relationship with the consumer and none of the... affiliate that has or has previously had a pre-existing business relationship with the consumer; or (ii)...

  6. 76 FR 79307 - Fair Credit Reporting (Regulation V)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... another continuing relationship) between the consumer and the person, during the 18-month period... by this subpart. (ii) Examples of pre-existing business relationships. (A) If a consumer has a time..., the financial institution has a pre-existing business relationship with the consumer and can...

  7. 12 CFR 41.21 - Affiliate marketing opt-out and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... relationship with the depository institution's securities affiliate for management of the consumer's securities... institution does not have a pre-existing business relationship with the consumer and none of the other... affiliate that has or has previously had a pre-existing business relationship with the consumer; or (ii)...

  8. 12 CFR 717.21 - Affiliate marketing opt-out and exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... federal credit union does not have a pre-existing business relationship with the consumer and none of the... business relationship with the consumer. (b) Making solicitations. (1) In general. For purposes of this... with a pre-existing business relationship it has or had with the consumer to market your products...

  9. 17 CFR 248.120 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-existing business relationships. (i) If a consumer has a brokerage account with a broker-dealer that is currently in force, the broker-dealer has a pre-existing business relationship with the consumer and can use... adviser, the investment adviser has a pre-existing business relationship with the consumer and can...

  10. THE COST-EFFECTIVENESS OF ALTERNATIVE INSTRUMENTS FOR ENVIRONMENTAL PROTECTION IN A SECOND-BEST SETTING. (R825313)

    EPA Science Inventory

    Abstract

    This paper employs analytical and numerical general equilibrium models to examine the significance of pre-existing factor taxes for the costs of pollution reduction under a wide range of environmental policy instruments. Pre-existing taxes imply significantly ...

  11. 12 CFR 41.20 - Scope and definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... that does not contain personal identifiers such as account numbers, names, or addresses. (4) Pre-existing business relationship—(i) In general. The term “pre-existing business relationship” means a relationship between a person, or a person's licensed agent, and a consumer based on— (A) A financial...

  12. A single black ulcer in a child with acute lymphocytic leukemia*

    PubMed Central

    Vestita, Michelangelo; Filoni, Angela; Santoro, Nicola; Arcamone, Gianpaolo; Bonamonte, Domenico

    2016-01-01

    Ecthyma gangrenosum is an uncommon dermatological manifestation characterized by round, indurated ulcers with a central necrotic black eschar and surrounding erythema. This report describes the case of a 5-year-old girl, affected by acute lymphocytic leukemia, presenting with a black eschar on her right thigh. Such lesions should always be correctly identified to avoid potentially fatal bacteraemia. Furthermore, because of its similar clinical presentation, cutaneous anthrax must be ruled out. PMID:28099607

  13. Failure strength of icy lithospheres

    NASA Technical Reports Server (NTRS)

    Golombek, M. P.; Banerdt, W. B.

    1987-01-01

    Lithospheric strengths derived from friction on pre-existing fractures and ductile flow laws show that the tensile strength of intact ice under applicable conditions is actually an order of magnitude stronger than widely assumed. It is demonstrated that this strength is everywhere greater than that required to initiate frictional sliding on pre-existing fractures and faults. Because the tensile strength of intact ice increases markedly with confining pressure, it actually exceeds the frictional strength at all depths. Thus, icy lithospheres will fail by frictional slip along pre-existing fractures at yeild stresses greater than previously assumed rather than opening tensile cracks in intact ice.

  14. Phytotherapy of chronic dermatitis and pruritus of dogs with a topical preparation containing tea tree oil (Bogaskin).

    PubMed

    Fitzi, J; Fürst-Jucker, J; Wegener, T; Saller, R; Reichling, J

    2002-05-01

    Localised dermatitis, for example unspecific eczema or skinfold pyoderma, is a very common diagnosis in dogs. Typical and impressive complaints are pruritus, erythema, erosion and oozing surface. With respect to the underlying disease dermatological treatment is indicated, usually based on antimicrobial and antipruriginous active substances, it can include transient glucocorticoids. An effective and safe alternative might be a phytotherapeutic topical preparation containing tea tree oil. Tea tree oil exerts both antimicrobial and antipruriginous effects. In an open multicenter study efficacy and safety of a standardized 10% tea tree oil cream applied thinly and twice daily for 4 weeks was tested in 53 dogs with chronic dermatitis, particularly non-specific eczema, allergic dermatitis, interdigital pyoderma, acral lick dermatitis and skinfold pyoderma. Analysis of efficacy assessed by investigating veterinarians showed a good or very good response to treatment for 82% of the dogs, significant at a 5% level (p = 0.05). At the end of the study a strong and significant reduction (p = 0.001) as well as disappearance of major symptoms were observed. Only two adverse events (local reactions) possibly related to tea tree oil occurred during therapy. Consequently the tested study medication (Bogaskin) can be considered an alternative for uncomplicated and localised dermatitis in dogs. Bogaskin might allow reduction of other pharmaceutical products, perhaps even replace standard therapy.

  15. Catheter Embolization

    MedlinePlus

    ... the scrotum that may be a cause of infertility. Catheter embolization may be used alone or combined ... in patients with diabetes or other pre-existing kidney disease. top of page What are the limitations of ...

  16. Acrolein-Induced Increases in Blood Pressure and Heart Rate Are Coupled with Decreased Blood Oxygen Levels During Exposure in Hypertensive Rats

    EPA Science Inventory

    Exposure to air pollution increases the risk of cardiovascular morbidity and mortality, especially in individuals with pre-existing cardiovascular disease. Recent studies link exposure to air pollution with reduced blood oxygen saturation suggesting that hypoxia is a potential me...

  17. Amifostine Pre-treatment Attenuates Lung Injury, But Not Inflammation, in Rats Intracheally Instilled with Particulate Matter Rich in Transition Metals

    EPA Science Inventory

    Exposure to particulate matter (PM) is associated with increased cardiovascular disease morbidity and mortality. These correlations are strengthened in individuals with pre-existing cardiovascular disease, including hypertension. Extensive evidence supports a significant role for...

  18. People Problems: The Human Component in PPBS

    ERIC Educational Resources Information Center

    Richards, James J.

    1972-01-01

    To avoid the dehumanization that can result from too much emphasis on efficiency alone, PPBS must conform with the pre-existing school environment, with its personal, political, social, and economic dimensions. (Editor)

  19. PARTICULATE MATTER, OXIDATIVE STRESS AND NEUROTOXICITY

    EPA Science Inventory

    Particulate matter (PM), a component of air pollution has been epidemiologically associated with sudden deaths, cardiovascular and respiratory illnesses. The effects are more pronounced in patients with pre-existing conditions such as asthma, diabetes or obstructive pulmonary dis...

  20. DIFFERENTIAL CARDIAC ARRHYTHMIA PROFILES IN HYPERTENSIVE AND NORMAL RATS AFTER EMISSION SOURCE PARTICULATE EXPOSURE

    EPA Science Inventory

    Exposure to combustion-derived fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. These effects are especially conspicuous in individuals with pre-existing cardiovascular diseases including hypertension and coronary heart disease...

  1. Opportunities and Limitations for Water Quality Improvement and Stream Restoration under SMCRA

    EPA Pesticide Factsheets

    Benefits of Remining are discussed including; reclamation of abandoned mine lands that the AML program is unlikely to ever restore, decrease or eliminate pollution loads of acidity,iron, manganese and other contaminants from pre-existing discharges.

  2. THE ROLE OF OXIDATIVE STRESS AND MITOCHONDRIA IN PARTICULATE MATTER (PM)-INDUCED CARDIOPULMONARY INJURY IN STROKE PRONE SPONTANEOUSLY HYPERTENSIVE (SHRSP) AND WISTAR KYOTO (WKY) RATS

    EPA Science Inventory

    Epidemiological studies have associated PM exposure with cardiovascular mortality and morbidity, and this effect seems to be enhanced in populations with pre-existing cardiovascular disease. One hypothesis for this exacerbation is that the higher underlying level of oxidative st...

  3. DIFFERENCES IN CARDIOVASCULAR RESPONSE TO PM EXPOSURE BETWEEN SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE (SHSP) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    ABSTRACT BODY: Epidemiological studies have shown that cardiovascular morbidity and mortality are associated with exposure to elevated levels of ambient particulate matter (PM), notably in people with pre-existing cardiopulmonary disease. To better understand the mechanisms of PM...

  4. Fine Ambient Air Particulate Matter Exposure Induces Molecular Alterations Indicative of Cardiovascular Disease Progression in Atherosclerotic Susceptible Mice -- B

    EPA Science Inventory

    Background: Epidemiology studies have reported associations between increased mortality and morbidity with exposure to particulate air pollution, particularly within individuals with pre-existing cardiovascular disease (CVD). Clinical and toxicological studies have provided evide...

  5. Aging Factsheets: Carbon Monoxide Poisoning Prevention

    EPA Pesticide Factsheets

    Everyone is at risk of being poisoned by carbon monoxide exposure. Older adults with pre-existing conditions, such as chronic heart disease, anemia, or respiratory problems, are even more susceptible to the effects of this odorless, colorless gas.

  6. The effects of ambient particulate matter on human alveolar machrophage oxidative and inflammatory responses

    EPA Science Inventory

    Epidemiologic and occupational studies demonstrate that ambient PM and DEP have deleterious effects on human cardiopulmonary health including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsivenes...

  7. Predictive modeling of synergistic effects in nanoscale ion track formation

    SciTech Connect

    Zarkadoula, Eva; Pakarinen, Olli H.; Xue, Haizhou; Zhang, Yanwen; Weber, William J.

    2015-08-05

    Molecular dynamics techniques and the inelastic thermal spike model are used to study the coupled effects of inelastic energy loss due to 21 MeV Ni ion irradiation and pre-existing defects in SrTiO3. We determine the dependence on pre-existing defect concentration of nanoscale track formation occurring from the synergy between the inelastic energy loss and the pre-existing atomic defects. We show that the nanoscale ion tracks’ size can be controlled by the concentration of pre-existing disorder. This work identifies a major gap in fundamental understanding concerning the role played by defects in electronic energy dissipation and electron–lattice coupling.

  8. Airways Hyperresponsiveness Following a Single Inhalation Exposure to Doxorubicin-Induced Heart Failure Prevents Airways Transition Metal-Rich Particulate Matter in Hypertensive Rats

    EPA Science Inventory

    Exposure to particulate matter (PM) air pollution results in airways hyperresponsiveness (AHR), however it also results in adverse cardiovascular effects, particularly in individuals with underlying cardiovascular disease. The impact of pre-existing cardiac deficit on PM-induced ...

  9. Energy Corner: Heat Reclamation Rescues Wasted Heat.

    ERIC Educational Resources Information Center

    Daugherty, Thomas

    1982-01-01

    Heat reclamation systems added to pre-existing central heating systems provide maximum savings at minimum cost. The benefits of a particular appliance marketed under the brand name "Energizer" are discussed. (Author/MLF)

  10. Particulate matter, oxidative stress and neurotoxicity.

    EPA Science Inventory

    Particulate matter (PM), a component of air pollution has been epidemiologically associated with sudden deaths, cardiovascular and respiratory illnesses. The effects are more pronounced in patients with pre-existing conditions such as asthma, diabetes or obstructive pulmonary dis...

  11. 26 CFR 1.436-1 - Limits on benefits and benefit accruals under single employer defined benefit plans.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Prior unpredictable contingent event. (c) Limitations on plan amendments increasing liability for... reduce funding balances. (b) Limitation on shutdown benefits and other unpredictable contingent event... regarding pre-existing plan provisions. (4) Exceptions. (5) Rule for determining when an amendment...

  12. Numerical simulation of the environmental impact of hydraulic fracturing of tight/shale gas reservoirs on near-surface ground water: background, base cases, shallow reservoirs, short-term gas and water transport

    EPA Pesticide Factsheets

    Researchers examined gas and water transport between a deep tight shale gas reservoir and a shallow overlying aquifer in the two years following hydraulic fracturing, assuming a pre-existing connecting pathway.

  13. Central retinal artery occlusion following forehead injection with a corticosteroid suspension.

    PubMed

    Edwards, Albert O

    2008-01-01

    Intralesional injection of corticosteroid suspensions into or adjacent to the ocular adnexa is performed by a number of medical specialists including dermatologists. Although not widely known outside of the ophthalmic community, these injections can lead to blindness through embolization of the central retinal artery. A case of blindness following injection into the forehead lesion of a child with the rare dermatologic condition pyogenic arthritis and pyodermic gangrenosum syndrome is reported. Injection into or near the ocular adnexa may be performed in small boluses to reduce the chance of retinal embolization following entry into the arterial system.

  14. Localization of immunoglobulins and complement by the peroxidase antiperoxidase method in autoimmune and non-autoimmune canine dermatopathies.

    PubMed

    Moore, F M; White, S D; Carpenter, J L; Torchon, E

    1987-01-01

    Formalin-fixed, paraffin embedded skin biopsy specimens from 44 dogs with various dermatopathies were examined for the presence of immunoglobulins (IgG, IgM, IgA) and complement (C3) by the peroxidase antiperoxidase method (PAP). Final diagnoses of the skin diseases were determined by clinical findings, fungal and bacterial cultures, skin scrapings, serum endocrinologic tests, and histologic features of cutaneous biopsies. The dermatopathies included examples of pyoderma (folliculitis/furunculosis), demodecosis, sarcoptic mange, dermatophytosis, endocrine dermatopathy, and autoimmune skin disease (AISD). In the latter category, 7 cases of pemphigus foliaceus, 1 pemphigus vulgaris, 4 discoid lupus erythematosus (DLE) and 4 examples of indeterminate AISD were examined. Immunoglobulins, C3, or both, were localized in tissue sections from AISD (15/16), pyoderma (7/11), demodecosis (4/8) sarcoptic mange (3/3), and dermatomycosis (2/3). Endocrine dermatopathy biopsies were consistently negative for Ig and C3 (0/3). The pattern of localization was most often intercellular (31/44 positive biopsies) with basement membrane immunoreactivity in 4 cases of DLE, and 1 case of indeterminate AISD. There was no consistent correlation between histologic features of hematoxylin and eosin-stained biopsies and the presence of Ig and C3. Clinical outcome was similar in both Ig and C3 positive and negative cases of non-AISD dermatitis. The high percentage (95%) of positive results in AISD biopsies indicates the usefulness and sensitivity of the PAP method for the localization of Ig and C3. Because of the high percentage of Ig localization in pyoderma (73%), biopsy specimens with extensive inflammatory skin disease are not suitable for diagnosis of AISD. The PAP method is useful in the diagnosis of AISD in biopsy specimens with minimal inflammation. Caution is warranted in the interpretation of immunoreactivity independent of clinical and histologic information.

  15. Genomic and Surface Proteomic Analysis of the Canine Pathogen Staphylococcus pseudintermedius Reveals Proteins That Mediate Adherence to the Extracellular Matrix ▿

    PubMed Central

    Bannoehr, Jeanette; Ben Zakour, Nouri L.; Reglinski, Mark; Inglis, Neil F.; Prabhakaran, Sabitha; Fossum, Even; Smith, David G.; Wilson, Gillian J.; Cartwright, Robyn A.; Haas, Juergen; Hook, Magnus; van den Broek, Adri H. M.; Thoday, Keith L.; Fitzgerald, J. Ross

    2011-01-01

    Cell wall-associated (CWA) proteins made by Gram-positive pathogens play a fundamental role in pathogenesis. Staphylococcus pseudintermedius is a major animal pathogen responsible for the canine skin disease bacterial pyoderma. Here, we describe the bioinformatic analysis of the family of 18 predicted CWA proteins encoded in the genome of S. pseudintermedius strain ED99 and determine their distribution among a phylogenetically diverse panel of S. pseudintermedius clinical isolates and closely related species of the Staphylococcus intermedius group. In parallel, we employed a proteomic approach to identify proteins presented on the surface of strain ED99 in vitro, revealing a total of 60 surface-localized proteins in one or more phases of growth, including 6 of the 18 genome-predicted CWA proteins. Based on these analyses, we selected two CWA proteins (SpsD and SpsL) encoded by all strains examined and investigated their capacity to mediate adherence to extracellular matrix proteins. We discovered that SpsD and SpsL mediated binding of a heterologous host, Lactococcus lactis, to fibrinogen and fibronectin and that SpsD mediated binding to cytokeratin 10, a major constituent of mammalian skin. Of note, the interaction with fibrinogen was host-species dependent, suggestive of a role for SpsD and SpsL in the host tropism of S. pseudintermedius. Finally, we identified IgG specific for SpsD and SpsL in sera from dogs with bacterial pyoderma, implying that both proteins are expressed during infection. The combined genomic and proteomic approach employed in the current study has revealed novel host-pathogen interactions which represent candidate therapeutic targets for the control of bacterial pyoderma. PMID:21576333

  16. Idiopathic Facial Aseptic Granuloma: Review of an Evolving Clinical Entity.

    PubMed

    Zitelli, Kristine B; Sheil, Amy T; Fleck, Robert; Schwentker, Ann; Lucky, Anne W

    2015-01-01

    Idiopathic facial aseptic granuloma (IFAG), originally termed pyodermite froide du visage, describes a generally asymptomatic facial nodule presenting in childhood with clinical resemblance to pyoderma or cystic, granulomatous, or vascular lesions. Clinical understanding is constantly evolving, with recent observations indicating that IFAG may represent a subtype of childhood rosacea. We present a case of IFAG associated with eyelid chalazions in a 19-month-old boy. Although his clinical course paralleled previously reported IFAG cases, we observed a unique ultrasound variation during initial diagnostic examination. Further delineation of clinical, imaging, and histologic properties of IFAG may reveal insights into etiologic associations and ideal management.

  17. [The epidemiology, diagnosis and prevention of dermatoses in workers manufacturing alumina from different aluminum ores].

    PubMed

    Podkin, Iu S

    1992-01-01

    Studies of dermatological morbidity in the workers of alumina enterprises showed a lowered incidence of skin lesions caused by common chemical harmfulness and increased incidence of allergic occupational dermatoses. Different types of such dermatoses are related to the ore used. The total level dermatologic morbidity mainly depends on the technology stage of the process but not on the type of raw material. Dermatologic screenings have shown that skin mycoses were the most incident among the dermatoses, whereas analysis of sick-leave records indicates the highest incidence of pyoderma; this necessitates adequate preventive measures.

  18. Endocrine alopecia in a miniature poodle.

    PubMed

    Allan, F J; Jones, B R; Purdie, E C

    1995-06-01

    Hypothyroidism and concurrent sex hormone imbalance associated with alopecia was diagnosed in a 5 year-old entire male Miniature Poodle. The dog had a 3-year history of alopecia, seborrhoea and recurrent superficial pyoderma. Abnormal thyrotropin releasing hormone stimulation test results supported a diagnosis of hypothyroidism. Partial hair regrowth occurred after interstitial cell tumours, which were present in both testicles, were removed by castration. Complete hair regrowth, however, occurred only after thyroid hormone supplementation. This case highlighted difficulties which may be encountered when interpreting serum hormone concentrations and endocrine function tests.

  19. Polymerase chain reaction based detection of Mycobacterium tuberculosis complex in lupus vulgaris: a case report.

    PubMed

    Baylan, O; Arca, E; Ozcan, A; Kisa, O; Albay, A; Doganci, L

    2004-09-01

    Lupus vulgaris (LV), the commonest of all forms of cutaneous tuberculosis, can affect the earlobes. Authors present a 20-year-old male patient with LV of the left earlobe initially misdiagnosed as pyoderma and treated superfluously with antibiotics at different intervals over the last 4 years in another hospital. Mycobacteria could not be seen or isolated by stained smears or conventional or radiometric culture methods from the skin biopsy specimens. Suspected clinical diagnosis of our patient was LV. This was supported by positive polymerase chain reaction assay and histological findings. The lesion was treated successfully with anti-tuberculosis chemotherapy, further confirming the diagnosis of LV.

  20. Rosacea fulminans: unusual clinical presentation of rosacea*

    PubMed Central

    Coutinho, Jessica Castiel; Westphal, Danielle Cristine; Lobato, Laís Cruz; Schettini, Antônio Pedro Mendes; Santos, Mônica

    2016-01-01

    Rosacea fulminans or pyoderma faciale is a rare cutaneous disorder that usually affects women usually between the ages of 15-46. The disease is characterized by sudden onset of papules, pustules, cysts, and painful coalescing nodules with red-cyanotic centrofacial erythema. Although its etiology remains unknown, hormonal, immunological, and vascular factors have been reported. Early diagnosis and prompt treatment should minimize unsightly scars. We report a case of a 33-year-old female patient treated with traditional doses of doxycycline, with improvement of the lesions and regression of the condition in two months. PMID:28300926