Pituitary Pars Intermedia Dysfunction and Metabolic Syndrome in Donkeys.

Appropriate medical care for donkeys is challenging despite being important working animals in non-industrialized countries and pets in first world countries. Although the same principles of diagnosis and therapy as in horses are commonly applied, there are differences in reference values and physiologic reaction to dynamic tests. However, donkeys seem to suffer from typical equine diseases, such as metabolic syndrome and pituitary pars intermedia dysfunction (PPID). Asinine metabolic syndrome (AMS) comprises obesity, insulin dysregulation, and laminitis. The principles of diagnosis are similar to horses. Donkey-specific reference ranges for insulin and glucose have been evaluated previously. Examinations regarding dynamic testing revealed differences in the intravenous glucose tolerance test and the combined insulin tolerance test compared to horses. The therapy of AMS is based mainly on weight loss and exercise. There are conflicting data regarding the incidence of PPID in donkeys. Laminitis and hypertrichosis were described as the main clinical signs. Species-specific and seasonal reference ranges were defined to diagnose PPID in donkeys. Furthermore, the dexamethasone suppression test, the thyrotropin releasing hormone (TRH) test and the combined dexamethasone suppression/TRH test were evaluated. Pergolide is commonly recommended for treatment.

Accidental Overdose of Pergolide (Prascend) Followed by Loss of Appetite, Tachycardia, and Behavioral Abnormalities in a Pony Mare.

A 26-year-old pony mare (ca. 180 kg bodyweight) was presented as an emergency because it had erroneously received 110 times its standard dose of pergolide (Prascend) per os approximately 4 hours earlier. Clinical examination initially was normal except tachycardia of 52 beats/min. The pony was treated symptomatically with paraffin oil and activated charcoal per nasogastric tube to prevent further systemic absorption and accelerate intestinal excretion of the pergolide. Furthermore, the pony received 400 mg of dopamine antagonist azaperone (Stresnil) intramuscularly (i.m.) followed by 80 mg every 6 hours twice i.m. and then 60 mg every 6 hours twice i.m. In addition, 40 mg verapamil (Verapamil-ratiopharm) was given every 4 hours per os for two days, followed by 40 mg every 6 hours for another 5 days. The pony was closely monitored clinically. It remained bright and alert with heart rate returning to normal within one day. The only abnormalities noticed 24 hours after ingestion of the pergolide overdose were a decreased appetite and anxiety, possibly a dopaminergic central nervous effect. Over the next days, appetite returned and anxiety disappeared. Overdosing pergolide is considered very rare and to the authors' knowledge this is the first report with a severe overdose of pergolide (Prascend). As accidental drug overdosing is a common error in medicine, it is important to know about possible side effects and how to react in cases like this.

Primary Hyperparathyroidism Associated With Atypical Headshaking Behavior in a Warmblood Gelding.

A 14-year-old Zweibrücker Warmblood gelding was presented for evaluation of lethargy and headshaking. The horse had a history of bouts of lameness in different limbs and back problems. It also had many mild colic episodes in the past. Results of repeat laboratory tests had shown persistent hypercalcemia (4.8 mmol/L; reference interval [RI]: 2.0-3.2 mmol/L) for 1.5 years and later on hypophosphatemia (0.4 mmol/L; RI: 0.5-1.3 mmol/L) and mild hypermagnesemia (1.0 mmol/L; RI: 0.5-0.9 mmol/L). Parathyroid hormone (PTH) concentration was within the RI. Other causes of hypercalcemia, such as renal failure, vitamin D toxicosis, and granulomatous disease, and nutritional secondary hyperparathyroidism were ruled out. Furthermore, there was no evidence of neoplastic disease. Parathyroid hormone-related protein was measured but inconclusive. A diagnosis of primary hyperparathyroidism was established on the basis of hypercalcemia, hypophosphatemia, low fractional excretion of calcium, and high fractional excretion of phosphorus in combination with a PTH secretion refractory to high calcium levels. Because of the bad prognosis, the owner decided to euthanize the horse. Results of postmortem examination were unremarkable. Hypercalcemia should always be considered abnormal, and further examinations need to be performed to proof hypercalcemia and subsequently find the cause. The main differential diagnoses are renal insufficiency and humoral hypercalcemia of malignancy, but also rare diseases, such as hyperparathyroidism, have to be taken into account.

Nasogastric Intubation as Health and Safety Risk in Equine Practice-A Questionnaire.

Placing a nasogastric tube can be a life-saving act for a horse but is considered an occupational hazard for veterinarians. An online questionnaire was performed to assess and specify potential risks. 123 equine veterinarians completed the survey, and the majority admitted using the mouth to handle the end of the nasogastric tube (sucking or blowing air) and having accidentally swallowed or aspirated stomach content or medications. This can potentially lead to aspiration pneumonia or pneumonitis. Mineral oil seems to be especially dangerous as aspiration may be asymptomatic at the beginning and lipoid pneumonitis may develop. Furthermore, 60% of responders would also handle the tube with their mouth if the horse was presented with fever and diarrhea or reflux formation, which might be affected by Salmonella sp. or Clostridium difficile producing toxins. The fact that nasogastric tubes are rarely being disinfected increases the risk of infection. 50% of veterinarians would use their mouth to suck or blow air into the tube during nasogastric intubation, even if the patient was presented with suspected poisoning. Rodenticide zinc phosphide is particularly dangerous as its breakdown product is a highly toxic gas. Inhalation leads to serious symptoms in humans, including pulmonary edema and neurological signs. Alternatives to mouth use (lavage, big syringe, or suction pump) when passing a tube should be considered, especially if a patient is presented with duodenitis-proximal jejunitis, diarrhea, or suspected poisoning. Awareness needs to be raised among veterinarians that nasogastric intubation is an extremely hazardous occupational practice.

Spray-drying of inhalable, multifunctional formulations for the treatment of biofilms formed in cystic fibrosis.

Cystic fibrosis (CF) is a serious lung disease, commonly susceptible to Pseudomonas aeruginosa colonization. The dense mucus together with biofilm formation limit drug permeability and prevent the drug from reaching the site of action, causing treatment failure of the bacterial infection. Besides the use of antibiotics, the mucolytic agent N-acetylcysteine (NAC) is recommended to be co-administered in the treatment of CF. Although several formulations have been developed for inhalation therapy to improve the pulmonary condition in CF patients, there is still no comprehensive study on a combined multifunctional dry powder formulation of antibiotics with NAC. In this work, we developed an innovative multifunctional dry powder inhaler (DPI) formulation based on salt formation between NAC and antibiotics and characterized their solid state properties and physical stability. NAC could be spray dried together with three different antibiotics, azithromycin (Azi), tobramycin (Tobra) and ciprofloxacin (Cipro), without the use of organic solvents to form Azi/NAC, Tobra/NAC and Cipro/NAC DPI formulations. Solid-state characterization of these DPI formulations showed that they were amorphous after spray drying. Azi/NAC and Tobra/NAC form co-amorphous salt systems that were physically stable under storage at stress conditions. For particle characterization, the obtained mass median aerodynamic diameters were in a suitable range for inhalation (< 5.0µm). The multifunctional antibiotic/NAC formulations conserved or improved the antibiotic susceptibility and showed promising results regarding the inhibition of P. aeruginosa PA14 biofilm formation.

Presumed Sulfonamide-Associated Uveitis With Stevens-Johnson Syndrome in a Quarter Horse Mare.

We describe the case of a four-year-old Quarter Horse mare that presented with fever, respiratory infection with productive cough, disorientation, and bilateral anterior uveitis with discharge that had been previously treated with trimethoprim-sulfadiazine (TMPS). Acinetobacter johnsonii was cultured from an endoscopic tracheal wash. Treatment was initiated with cefquinome, systemic flunixin-meglumine, local ocular atropine, and corticosteroids. On subsequent days, the mare exhibited bilateral edematous, painful swelling of the face, primarily affecting the eyelids and lips. There were neither swellings nor pulsations of the metatarsal arteries. On day five of treatment, the facial swelling disappeared, the uveitis improved markedly, and the mare's periorbital skin, muzzle, and vulva began to slough, revealing underlying, nonpigmented skin. Although systemic use of sulfonamides has been associated with bilateral anterior uveitis and Stevens-Johnson syndrome (SJS or erythema multiforme major) in humans, these conditions are rare in horses. Stevens-Johnson syndrome has been associated most commonly with sulfonamide use but also with a range of other medications, including anti-infectives, anti-inflammatories, anticonvulsants, analgesics, and infections. A possible pathway for sulfonamide-induced SJS is discussed. To our knowledge, this is the first reported case of sulfonamide-associated uveitis and SJS in the horse.

Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections.

Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu-3 cells and CF bronchial epithelial cells (CFBE41o-) indicated that complex-loaded PLGA NPs were non-toxic at concentrations ≫ MICcipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex-loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung.

Preference for luminance histogram regularities in natural scenes.

Natural scene luminance distributions typically have positive skew, and for single objects, there is evidence that higher skew is a correlate (but not a guarantee) of glossiness. Skewness is also relevant to aesthetics: preference for glossy single objects (with high skew) has been shown even in infants, and skewness is a good predictor of fruit freshness. Given that primate vision appears to efficiently encode natural scene luminance variation, and given evidence that natural scene regularities may be a prerequisite for aesthetic perception in the spatial domain, here we ask whether humans in general prefer natural scenes with more positively skewed luminance distributions. If humans generally prefer images with the higher-order regularities typical of natural scenes and/or shiny objects, we would expect this to be the case. By manipulating luminance distribution skewness (holding mean and variance constant) for individual natural images, we show that in fact preference varies inversely with increasing positive skewness. This finding holds for: artistic landscape images and calibrated natural scenes; scenes with and without glossy surfaces; landscape scenes and close-up objects; and noise images with natural luminance histograms. Across conditions, humans prefer images with skew near zero over higher skew images, and they prefer skew lower than that of the unmodified scenes. These results suggest that humans prefer images with luminances that are distributed relatively evenly about the mean luminance, i.e., images with similar amounts of light and dark. We propose that our results reflect an efficient processing advantage of low-skew images over high-skew images, following evidence from prior brain imaging results.

Equine multinodular pulmonary fibrosis (EMPF): Five case reports.

Equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing interstitial lung disease has been associated with gammaherpesviruses. This case series describes five horses with EMPF. Three of the horses (two in Hungary, one in the Czech Republic) were diagnosed with EMPF ante mortem. They presented with typical clinical signs of EMPF including dyspnoea and weight loss. Arterial blood gas analysis revealed hypoxaemia. Blood work showed signs of inflammation like neutrophilia and hyperfibrinogenaemia. An endoscopic examination of the respiratory tract including cytology and culture of tracheobronchial secretion and bronchoalveolar lavage were performed, revealing secondary bacterial infection in one case. A suspected diagnosis of EMPF was made on the basis of a positive EHV-5 PCR from bronchoalveolar lavage and the findings of thoracic radiographs and ultrasound examination. In one case the diagnosis was confirmed by lung biopsy. All horses died or had to be euthanised despite treatment. Two horses (from Austria) were diagnosed with EMPF post mortem. They not only had EMPF but also concurrent other diseases which seemed to be associated with immunosuppression. Three horses showed the discrete form and two horses the diffuse form of EMPF. EHV-5 DNA was identified in lung tissue of all horses by PCR.

Diagnostic value of the neutrophil myeloperoxidase index in horses with systemic inflammation.

The myeloperoxidase index (MPXI) was investigated as a diagnostic indicator of systemic inflammation in a retrospective study using data from 859 hospitalised horses. A reference interval of 8.5-10.4 for the MPXI was established. In horses with systemic inflammatory response syndrome (SIRS), the MPXI was significantly lower than in healthy horses, those with localised inflammation and those with sepsis. The MPXI in horses with sepsis was also significantly lower than in healthy animals and those with localised inflammation. Horses in the SIRS group with leucopenia, white blood cell (WBC) count within the reference interval (WRI) or leucocytosis had significantly lower MPXIs than healthy horses, those with localised inflammation and those with sepsis in the same WBC count subgroups. In horses with sepsis and WBC count WRI, the MPXI was significantly lower than in healthy horses or those with localised inflammation. MPXI is a useful complementary tool to identify horses with systemic inflammation, especially if they have WBC counts WRI.

Cutaneous fungal granuloma in a horse.

This case report describes a 4-year-old-horse with two cutaneous masses on the right crest of the neck. Biopsy revealed chronic nodular pyogranulomatous dermatitis and panniculitis. Giemsa and periodic acid-Schiff stains showed focal spherical, yeast-like organisms. A diagnosis of cutaneous fungal granuloma was made. The size of the masses decreased after oral treatment with fluconazole for 10 days combined with potassium iodide for 30 days, and the remaining masses were excised by laser. Lesions did not recur at the site. Fungal granuloma should be considered as a differential diagnosis in horses with cutaneous or subcutaneous nodules. A definitive diagnosis can only be achieved by histopathological examination or by culture of the affected tissue.

Keratoconjunctivitis sicca attributable to parasympathetic facial nerve dysfunction associated with hypothyroidism in a horse.

CASE DESCRIPTION: A 6-year-old 680-kg (1,496-lb) German Warmblood gelding was evaluated because of bilateral blepharospasm and head shaking. CLINICAL FINDINGS: Moderate blepharospasm was evident bilaterally, and both eyes had hyperemic and edematous conjunctivas and lusterless corneas. For each eye, the Schirmer tear test value was only 7 mm/min. The horse's nasal mucosa was dry. Abnormal behaviors included mild repetitive vertical movement of the head, snorting, and flehmen response (classic signs of head shaking). Touching the horse's nostrils and face revealed paresthesia and dysesthesia with slight nasolabial muscle hypertrophy bilaterally. Cranial nerve examination revealed no other abnormalities. Serum thyroxine concentration was low, and results of thyrotropin-releasing hormone and thyroid-stimulating hormone stimulation tests were negative, indicating that the horse had hypothyroidism. The diagnoses included keratoconjunctivitis sicca and dry nares attributable to parasympathetic facial nerve dysfunction, head-shaking syndrome with paresthesia and dysesthesia of the face attributable to sensory trigeminal nerve disorder, and hypothyroidism. The 2 nerve dysfunctions were considered peripheral neuropathies that were most likely caused by hypothyroidism. TREATMENT AND OUTCOME: Treatment of both eyes was initiated with topical applications of cyclosporine, 0.5% sodium hyaluronate, and vitamin A ointment. Levothyroxine (20 microg/kg [9.1 microg/lb], PO, q 24 h) was administered. Within 3 weeks to 4 months, serum thyroxine concentration was within reference range, and clinical signs and Schirmer tear test values improved. CLINICAL RELEVANCE: Hypothyroidism should be considered as a differential diagnosis in horses with peripheral neuropathy or keratoconjunctivitis sicca. In affected horses, administration of levothyroxine may lead to resolution of neurologic signs.

Adjuvant immunotherapy of feline fibrosarcoma with recombinant feline interferon-omega.

BACKGROUND: Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. HYPOTHESIS: Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible. ANIMALS: Twenty domestic cats. METHODS: In an open-labeled uncontrolled clinical trial 12 injections of 1 x 10(6) U/kg rFeIFN-omega were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-omega. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-omega and recombinant feline interferon-gamma was performed to assess the biological effect of rFeIFN-omega. RESULTS: Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P = .025), neutropenia (P = .021), and weight loss (P < .001) were statistically correlated with rFeIFN-omega-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-omega). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P = .026) in response to in vitro incubation with rFeIFN-omega, whereas expression of MHC class II molecules was not affected significantly. CONCLUSIONS AND CLINICAL IMPORTANCE: RFeIFN-omega for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.