Mefenoxam, Itraconazole, and Terbinafine Combination Therapy for Management of Pythiosis in Dogs (Six Cases)

2020 ◽  
Vol 56 (6) ◽  
pp. 307
Author(s):  
Harry Cridge ◽  
Samantha M. Hughes ◽  
Vernon C. Langston ◽  
Andrew J. Mackin

ABSTRACT Pythium insidiosum is an oomycete that encysts in the skin or gastrointestinal tract, leading to pythiosis. Pythiosis is reported in tropical and subtropical climates, affecting dogs and rarely cats. Surgical resection is the treatment of choice; however, cases present late in the disease and lesions are often nonresectable. Medical management is typically unsuccessful, with uncommon exceptions; however, mefenoxam, an agricultural fungicide, has in vitro efficacy against P insidiosum. We describe the use of mefenoxam, itraconazole, and terbinafine (MIT) in five dogs with gastrointestinal pythiosis and one dog with cutaneous pythiosis. Two of the gastrointestinal cases had disease extending to surgical margins and received MIT: resolution of clinical signs and seronegativity occurred after 189–193 days. Another case underwent surgical resection and MIT. The dog improved but subsequently developed a rectal mass, which responded to addition of prednisone and immunotherapy. Two cases were treated with MIT alone, and response varied. Efficacy of MIT in cutaneous pythiosis could not be determined. MIT may result in improved survival and seronegativity in dogs with incompletely resected gastrointestinal pythiosis. Mefenoxam is EPA registered, and extralabel use under the Animal Medicinal Drug Use Clarification Act does not apply. Additional research is recommended before use.

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Abtin Mojarradi ◽  
Sofie Van Meervenne ◽  
Alejandro Suarez-Bonnet ◽  
Steven De Decker

Abstract Background Naso-ethmoidal meningoencephalocele is usually a congenital anomaly consisting of a protrusion of cerebral tissue and meninges into the ethmoidal labyrinth. The condition is a rare cause of structural epilepsy in dogs. We report the clinical presentation, surgical intervention, postoperative complications and outcome in a dog with drug resistant epilepsy secondary to a meningoencephalocele. Case presentation A 3.3-year-old male neutered Tamaskan Dog was referred for assessment of epileptic seizures secondary to a previously diagnosed left-sided naso-ethmoidal meningoencephalocele. The dog was drug resistant to medical management with phenobarbital, potassium bromide and levetiracetam. Surgical intervention was performed by a transfrontal craniotomy with resection of the meningoencephalocele and closure of the dural defect. Twenty-four hours after surgery the dog demonstrated progressive cervical hyperaesthesia caused by tension pneumocephalus and pneumorrhachis. Replacement of the fascial graft resulted in immediate resolution of the dog’s neurological signs. Within 5 months after surgery the dog progressively developed sneezing and haemorrhagic nasal discharge, caused by sinonasal aspergillosis. Systemic medical management with oral itraconazole (7 mg/kg orally q12h) was well-tolerated and resulted in resolution of the clinical signs. The itraconazole was tapered with no relapsing upper airway signs. The dog’s frequency of epileptic seizures was not affected by surgical resection of the meningoencephalocele. No treatment adjustments of the anti-epileptic medication have been necessary during the follow-up period of 15 months. Conclusions Surgical resection of the meningoencephalocele did not affect the seizure frequency of the dog. Further research on prognostic factors associated with surgical treatment of meningoencephaloceles in dogs is necessary. Careful monitoring for postsurgical complications allows prompt initiation of appropriate treatment.


2019 ◽  
Vol 57 (8) ◽  
pp. 923-928 ◽  
Author(s):  
Nitipong Permpalung ◽  
Navaporn Worasilchai ◽  
Kasama Manothummetha ◽  
Pattama Torvorapanit ◽  
Kitiya Ratanawongphaibul ◽  
...  

Abstract Ocular pythiosis is the second most common form of human pythiosis, and the rates of evisceration/enucleation in Thailand are 55–79%. This prospective study was conducted to evaluate treatment outcomes of the combination therapy protocol and the potential use of serum (1→3)-β-glucan (BG) and Pythium insidiosum-specific antibody (Pi-Ab) as an aid to diagnosis and monitoring of ocular pythiosis. Thirty patients were enrolled in the study and 14 (non-globe salvage) required evisceration/enucleation. The globe salvage group was significantly younger, and first ocular surgeries were performed significantly sooner than in the non-globe salvage group. Serum BG and Pi-Ab levels were similar among the 2 groups over time. In vitro susceptibility testing of antifungal agents revealed relatively high minimum inhibitory concentrations and lack of synergistic effect. Serum BG and Pi-Ab would not be useful in diagnosis and monitoring of ocular pythiosis. Until effective antimicrobial agents are discovered, ocular surgeries are still the mainstay therapy in Thailand.


1999 ◽  
Vol 35 (2) ◽  
pp. 107-110 ◽  
Author(s):  
ME Reimer ◽  
MS Leib ◽  
MS Reimer ◽  
GK Saunders ◽  
SA Johnston

An 18-month-old, spayed female Australian terrier cross was presented with a 10-month history of chronic large bowel diarrhea. Ulceration and two proliferative masses in the rectum were seen on colonoscopy. Surgical resection was performed to remove the masses, and the dog recovered without complications related to surgery. Histopathology was consistent with the diagnosis of ganglioneuroma. The dog had no clinical signs of disease within three months of surgery and was completely normal 2.5 years after diagnosis. This is the first report providing follow-up and successful outcome of a ganglioneuroma in the gastrointestinal tract of a dog.


2020 ◽  
Vol 48 ◽  
Author(s):  
Taiara Müller da Silva ◽  
Mariana Martins Flores ◽  
Eryca Ceolin Lamego ◽  
Douglas Miotto Lorenzetti ◽  
Cristina Prade Ramos ◽  
...  

Background: Pythiosis is an infectious disease caused by the oomycete Pythium insidiosum, with higher occurrence in wetlands and hot climate regions. This microorganism develops its cycle in aquatic plants, and most cases happen because of the contact of animals or people with water containing the motile zoospores (infectious form). Horses are the principal species affected and develop principally cutaneous and subcutaneous lesions, but the gastrointestinal tract is seldom affected. Humans develop various forms of pythiosis, such as a vascular form. The objectives of the current study are to describe an unusual case of intestinal pythiosis, its clinical signs, aspects of pathogenesis, and diagnosis.Case: A 13-year-old Crioula mare, from Santa Maria, RS, Brazil, presented with reduced food and water intake, apathy, restlessness, rolling, nasal reflux, firm abdomen upon palpation, and tachypnea during 2 days. The horses of this farm were fed native pasture and horse feed, and they had access to a nearby pond. Two days following the start of the clinical signs, the horse died and was necropsied on the farm. During necropsy, there was around 400 mL of reddish effusion in the abdominal cavity (modified transudate). A 15 cm segment of jejunum was firm upon palpation and had a severe transmural thickening. The wall of the affected area was up to 3 cm in thickness and firm, with small yellowish and irregular masses that stood out and looked friable, interpreted as kunkers. Microscopically, the yellowish masses (kunkers) were characterized by dense accumulations of intact and degenerate eosinophils (eosinophilic necrosis). Within these kunkers, and also on their periphery, there were multiple negatively stained hyphal profiles. Hyphae were also seen on the wall of small arteries inside the kunkers. These hyphae had nearly parallel walls and were occasionally septate, with a diameter of about 10 μm. The hyphae stained black with Grocott’s methenamine silver stain (GMS) and were positive on immunohistochemistry (IHC) using specific anti-P. insidiosum polyclonal antibody.Discussion: Colic is the principal clinical presentation in horses suffering from gastrointestinal tract disorders. In spite of the presence of colic in this horse, intestinal pythiosis was not clinically suspected in this case, principally because of its rare occurrence in horses. Even though it is persistent to observe horses ingesting water with suspected contamination by P. insidiosum, the cutaneous form of pythiosis is a lot more common than the intestinal form. This is the only case of intestinal pythiosis in a horse in 52 years of routine diagnosis in our laboratory. It is suspected that this horse got infected by drinking contaminated water from the nearby pond and microlesions in the intestinal mucosa due to plant material or some unknown pathogen may have favored zoospore adhesion, encysting and starting the colonization of the tissue by emitting a germ tube. A macroscopic observation of kunkers in the intestine is rare, but when observed it is highly indicative of pythiosis. The immunohistochemistry technique using anti-P. insidiosum antibody, in accordance with the literature, validates the diagnosis of pythiosis. In this case, the presence of hyphae in the blood vessel wall inside the kunkers propose that this finding may be involved in the spread of the lesion but needs more detailed studies.


2020 ◽  
Vol 187 (4) ◽  
pp. e29-e29 ◽  
Author(s):  
Juliana de Moura Alonso ◽  
Gustavo dos Santos Rosa ◽  
Bruna Santos ◽  
Simony Guerra ◽  
Márcio Ribeiro ◽  
...  

BackgroundIntraperitoneal administration of ceftriaxone maintains therapeutic abdominal concentrations for 24 hours in healthy horses. Therefore, it is a possible treatment for septic peritonitis. The aim of this study was to evaluate the efficacy of ceftriaxone as an adjuvant treatment in horses with septic peritonitis.MethodsTwenty-six horses with clinical signs, sonography and/or laboratory findings of septic peritonitis were included. Peritoneal fluid was collected for microbiological culture and in vitro microbial sensitivity profile assessment. Daily intraperitoneal administration of ceftriaxone (25 mg/kg) was initiated with supportive and systemic antimicrobial treatment. The animals were divided into three groups: group 1—gastrointestinal tract injuries and abdominal surgery (excluding perforations/ruptures); group 2—not related to changes in the gastrointestinal tract; group 3—secondary to intestinal rupture and/or faeces contamination.ResultsThe mean success rate of the treatment was 77 per cent (20/26 animals), with success rates of 84.6 per cent in group 1; 87.5 per cent, group 2; and 40 per cent, group 3.ConclusionsThis is the first study to report adjuvant intraperitoneal treatment ceftriaxone for septic peritonitis in horses and indicates that this treatment can successfully treat septic peritonitis in horses.


2007 ◽  
Vol 13 (5) ◽  
pp. 596-609 ◽  
Author(s):  
FG Mastronardi ◽  
H. Tsui ◽  
S. Winer ◽  
DD Wood ◽  
T. Selvanantham ◽  
...  

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol®) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS. Multiple Sclerosis 2007; 13: 596-609. http://msj.sagepub.com


Author(s):  
Ф.М. Шакова ◽  
Т.И. Калинина ◽  
М.В. Гуляев ◽  
Г.А. Романова

Цель исследования - изучение влияния комбинированной терапии (мутантные молекулы эритропоэтина (EPO) и дипептидный миметик фактора роста нервов ГК-2H) на воспроизведение условного рефлекса пассивного избегания (УРПИ) и объем поражения коры мозга у крыс с двусторонним ишемическим повреждением префронтальной коры. Методика. Мутантные молекулы EPO (MЕРО-TR и MЕPО-Fc) с значительно редуцированной эритропоэтической и выраженной цитопротекторной активностью созданы методом генной инженерии. Используемый миметик фактора роста нервов человека, эндогенного регуляторного белка, в экспериментах in vitro проявлял отчетливые нейропротективные свойства. Двустороннюю фокальную ишемию префронтальной коры головного мозга крыс создавали методом фотохимического тромбоза. Выработку и оценку УРПИ проводили по стандартной методике. Объем повреждения мозга оценивался при помощи МРТ. MEPO-TR и MEPO-Fc (50 мкг/кг) вводили интраназально однократно через 1 ч после фототромбоза, ГК-2Н (1 мг/кг) - внутрибрюшинно через 4 ч после фототромбоза и далее в течение 4 послеоперационных суток. Результаты. Выявлено статистически значимое сохранение выработанного до ишемии УРПИ, а также значимое снижение объема повреждения коры при комплексной терапии. Полученные данные свидетельствуют об антиамнестическом и нейропротекторном эффектах примененной комбинированной терапии, которые наиболее отчетливо выражены в дозах: МEPO-Fc (50 мкг/кг) и ГК-2Н (1 мг/кг). Заключение. Подтвержден нейропротекторный эффект и усиление антиамнестического эффекта при сочетанном применении мутантных производных эритропоэтина - MEPO-TR и MEPO-Fc и дипептидного миметика фактора роста нервов человека ГК-2H. The aim of this study was to investigate the effect of combination therapy, including mutant erythropoietin molecules (EPO) and a dipeptide mimetic of the nerve growth factor, GK-2H, on the conditioned passive avoidance (PA) reflex and the volume of injury induced by bilateral ischemia of the prefrontal cortex in rats. Using the method of genetic engineering the mutant molecules of EPO, MERO-TR and MEPO-Fc, with strongly reduced erythropoietic and pronounced cytoprotective activity were created. The used human nerve growth factor mimetic, an endogenous regulatory protein based on the b-bend of loop 4, which is a dimeric substituted dipeptide of bis- (N-monosuccinyl-glycyl-lysine) hexamethylenediamine, GK-2 human (GK-2H), has proven neuroprotective in in vitro experiments. Methods. Bilateral focal ischemic infarction was modeled in the rat prefrontal cortex by photochemically induced thrombosis. The PA test was performed according to a standard method. Volume of brain injury was estimated using MRI. MEPO-TR, and MEPO-Fc (50 mg/kg, intranasally) were administered once, one hour after the injury. GK-2Н (1 mg/kg, i.p.) was injected four hours after the injury and then for next four days. Results. The study showed that the complex therapy provided statistically significant retention of the PA reflex developed prior to ischemia and a significant decrease in the volume of injury. The anti-amnestic and neuroprotective effects of combination therapy were most pronounced at doses of MEPO-Fc 50 mg/kg and GK-2H 1 mg/kg. Conclusion. This study has confirmed the neuroprotective effect and enhancement of the anti-amnestic effect exerted by the combination of mutant erythropoietin derivatives, MEPO-TR and MEPO-Fc, and the dipeptide mimetic of human growth factor GK-2H.


2020 ◽  
Vol 22 (10) ◽  
pp. 675-682 ◽  
Author(s):  
Jie Yin ◽  
Zhongping Qin ◽  
Kai Wu ◽  
Yufei Zhu ◽  
Landian Hu ◽  
...  

Backgrounds and Objective: Blue rubber bleb nevus syndrome (BRBN) or Bean syndrome is a rare Venous Malformation (VM)-associated disorder, which mostly affects the skin and gastrointestinal tract in early childhood. Somatic mutations in TEK have been identified from BRBN patients; however, the etiology of TEK mutation-negative patients of BRBN need further investigation. Method: Two unrelated sporadic BRBNs and one sporadic VM were firstly screened for any rare nonsilent mutation in TEK by Sanger sequencing and subsequently applied to whole-exome sequencing to identify underlying disease causative variants. Overexpression assay and immunoblotting were used to evaluate the functional effect of the candidate disease causative variants. Results: In the VM case, we identified the known causative somatic mutation in the TEK gene c.2740C>T (p.Leu914Phe). In the BRBN patients, we identified two rare germline variants in GLMN gene c.761C>G (p.Pro254Arg) and c.1630G>T(p.Glu544*). The GLMN-P254R-expressing and GLMN-E544X-expressing HUVECs exhibited increased phosphorylation of mTOR-Ser-2448 in comparison with GLMN-WTexpressing HUVECs in vitro. Conclusion: Our results demonstrated that rare germline variants in GLMN might contribute to the pathogenesis of BRBN. Moreover, abnormal mTOR signaling might be the pathogenesis mechanism underlying the dysfunction of GLMN protein.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Takuhisa Okada ◽  
Yasumitsu Hirano ◽  
Shintaro Ishikawa ◽  
Hiroka Kondo ◽  
Toshimasa Ishii ◽  
...  

Abstract Background Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLTGT) is extremely rare. It is a mesenchymal neoplasm that usually forms in the small intestine of adolescents and young adults, is prone to local recurrence and metastasis, and has a high mortality rate. We report a patient with CCSLTGT with lymph node- and liver metastases, who continues to survive 6 years after initial surgical resection. Case presentation A 38-year-old woman presented with lightheadedness. Laboratory analysis revealed anemia (hemoglobin, 6.7 g/dL), and enhanced computed tomography (CT) demonstrated a mass in the small intestine, about 6 cm in diameter, with swelling of 2 regional lymph nodes. Double-balloon small intestine endoscopic examination revealed a tumor accompanied by an ulcer; the biopsy findings suggested a primary cancer of the small intestine. She was admitted, and we then performed a laparotomy for partial resection of the small intestine with lymph node dissection. Pathologic examination revealed CCSLTGT with regional lymph node metastases. About 3 years later, follow-up CT revealed a single liver metastasis. Consequently, she underwent a laparoscopic partial liver resection. Histopathologic examination confirmed that the liver metastasis was consistent with CCSLTGT. It has now been 3 years without a recurrence. Conclusion Repeated radical surgical resection with close follow-up may be the only way to achieve long-term survival in patients with CCLSTGT.


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