Evaluation of the clinical efficacy of subconjunctival injection of clindamycin in the treatment of naturally occurring infectious bovine keratoconjunctivitis

OBJECTIVE: To determine the clinical efficacy of subconjunctival injection of clindamycin in the treatment of naturally occurring infectious bovine keratoconjunctivitis (IBK). ANIMALS STUDIED: Clinically, out of 81 animals examined, 46 were found to be suffering from IBK of variable severity. The ocular secretions were collected and cultured for Moraxella bovis. The study included 36 Holstein cattle from which M. Bovis was isolated. These animals ranged between 4 and 28 months of age. PROCEDURES: The severity of the clinical findings were scored as normal, mild, moderate, and severe. Clindamycin was injected subconjunctivally at a total dose of 150 mg (1 mL), once daily for 3 days to the test group (n = 18); isotonic saline solution (1 mL) was administered to the control group. After treatment, all cattle were re-examined and clinical response was evaluated on days 3, 7 and 15 post-treatment. RESULTS: Compared with the control group and prior to treatment, all active lesions such as blepharospasm, epiphora, photophobia, chemosis, corneal edema, and corneal ulceration were generally resolved by day 15 after subconjunctival injection of clindamycin. Severity of IBK lesions increased on days 3 and 7, compared to baseline in the control group administered isotonic saline solution. CONCLUSIONS: The results of this study suggest that subconjunctival injection of clindamycin is effective in the treatment of naturally occurring infectious bovine keratoconjunctivitis.     

内镜直视下气囊扩张联合A型肉毒毒素注射治疗贲门失弛缓症32例分析

目的探讨内镜直视下气囊扩张术联合A型肉毒毒素(botulinum toxin A,BTXA)注射序贯治疗贲门失弛缓症近期及远期疗效。方法收集1999-07~2007-05在我院确诊的行内镜下气囊扩张术联合肉毒素注射治疗的贲门失弛缓症患者32例,于治疗后1、3、6、12个月随访观察患者的临床症状、贲门口内径、5min存留钡柱高度等。结果所有患者术后吞咽困难消失或明显改善,随访1、3、6、12个月有效率分别为100%、96.88%、87.50%和74.19%。结论气囊扩张术联合内镜下肉毒毒素注射序贯治疗贲门失弛缓症,操作安全,近远期疗效好,治疗费用经济。     

Effects of topical administration of 0.005% latanoprost solution on eyes of clinically normal horses.

OBJECTIVE: To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration. ANIMALS: 20 adult clinically normal horses. PROCEDURE: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora, blepharospasm, blepharedema, and aqueous flare were recorded prior to IOP measurement. RESULTS: IOP was reduced from baseline by a mean value of 1.03 mm Hg (5%) in males and 3.01 mm Hg (17%) in females during the treatment period. Miosis developed in all treated eyes and was moderate to marked in 77% of horses, with the peak effect observed 4 to 8 hours after drug administration. Conjunctival hyperemia, epiphora, blepharospasm, and blepharedema were present in 100, 57, 42, and 12% of treated eyes, respectively, 2 to 24 hours following drug administration. Aqueous flare was not observed at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Although IOP was reduced with every 24-hour dosing of latanoprost, the frequency of prostaglandin-induced adverse events was high. Because recurrent uveitis appears to be a risk factor for glaucoma in horses, topical administration of latanoprost may potentiate prostaglandin-mediated inflammatory disease in affected horses.     

A Clostridium botulinum type B vaccine for prevention of shaker foal syndrome

A toxoid was prepared from type B toxin of Clostridium botulinum by treatment with 0.6% formalin for 6 weeks. The toxoid was adsorbed to aluminium hydroxide and this vaccine was evaluated for safety in guinea pigs, mice and horses, and for immunogenicity in guinea pigs and horses. Neutralising antitoxin was demonstrated in adult horses receiving two 2 ml subcutaneous doses 6 weeks apart, and in a foal which suckled its vaccinated dam. Another vaccinated mare and the passively immunised foal were protected against subcutaneous injection of 1600 and 2000 mouse lethal doses of toxin per kg respectively.     

Limbal conjunctival plaques and idiopathic eosinophilic conjunctivitis

A 4‐year‐old Welsh pony crossbred gelding was examined for acute onset of blepharospasm, epiphora and corneal oedema. Ophthalmic examination identified 2 conjunctival plaques located near the superior limbus of the left eye. The plaques did not resolve following treatment with topical triple antibiotic ointment, topical atropine ointment and oral flunixin meglumine and therefore a conjunctival biopsy was performed. Histology of the biopsy resulted in a diagnosis of eosinophilic conjunctivitis, which was treated with a topical corticosteroid ointment. Plaques resolved after 73 days of therapy but lesions did not improve with concurrent treatment with anthelmintics early in the course of therapy. Failure to identify an aetiological agent led to a diagnosis of idiopathic eosinophilic conjunctivitis. The conjunctival plaques have not recurred in the 10 months following discontinuation of therapy.     

Unicentric extranodal lymphoma of the upper eyelid conjunctiva in a dog

A case of conjunctival lymphoma in a 4-year-old Siberian husky is reported. A large red mass protruding from the conjunctiva of the upper eyelid of the right eye was present. Irritation, blepharospasm and epiphora were revealed on initial ophthalmic examination. After anti-inflammatory treatment, surgery was performed. Histologically, the mass consisted of large polygonal cells with a high nucleus to cytoplasm ratio, moderate amounts of slightly eosinophilic cytoplasm, pleomorphic nuclei with vesicular chromatin and prominent multiple nucleoli. Mitotic figures were frequent. Approximately 70% of the neoplastic cells were CD3 positive and CD79alpha negative. On the basis of histologic and immunohistochemical findings, a diagnosis of intermediate-grade, diffuse large-cell lymphoma with T-cell immunophenotype was made. The surgical area healed uneventfully and, although chemotherapy was not received, after 12 months the dog exhibited no recurrence. To the authors' knowledge, this is the first report of unicentric extranodal conjunctival lymphoma in a dog.     

Effects of injection of botulinum toxin type B into the external anal sphincter on anal pressure of horses

OBJECTIVE: To determine effects on anal pressure of horses after local injection of the external anal sphincter with Clostridium botulinum toxin type B. ANIMALS: 11 healthy adult horses. PROCEDURE: Peak and resting anal sphincter pressures were measured with a custom-made rectal probe that was connected to a pressure transducer. Pressures were measured before treatment and after injection with botulinum toxin type B (BTB) or saline (0.9% NaCl) solution. Dose titration with 500, 1,000, 1,500, and 2,500 U of BTB was completed. Physical changes, behavior, and anal pressure were recorded for each horse. RESULTS: Injection of 1,000 U of BTB caused a significant reduction in peak anal pressure from days 2 to 84, compared with pressure in control horses. Maximal effect of the toxin was observed within the first 15 days after injection, followed by a slow return to baseline during the 168-day period. Injection of 2,500 U of BTB in the anal sphincter in 1 horse resulted in lethargy, generalized weakness, and dysphagia for 14 days. Adverse clinical effects were not observed in horses after injections with 500, 1,000, or 1,500 U of BTB. CONCLUSIONS AND CLINICAL RELEVANCE: The effect of focal intramuscular injection of BTB in horses is similar to that reported for other species. However, horses appear to be more sensitive to BTB, compared with other species, and clinical signs of botulism may develop at doses exceeding 1,500 U. Injections of BTB in the external anal sphincter of mares may be useful to reduce incisional dehiscence after repair of perineal lacerations.     

Effects of 0.005% latanoprost solution on intraocular pressure in healthy dogs and cats

OBJECTIVE: To evaluate effects of daily topical ocular administration of latanoprost solution on intraocular pressure (IOP) in healthy cats and dogs. ANIMALS: 9 domestic shorthair cats and 14 dogs. PROCEDURE: Latanoprost solution (0.005%) was administered topically to 1 eye (treated) and vehicle to the other eye (control) of all animals once daily in the morning for 8 days. Intraocular pressure was measured twice daily for the 5 days preceding treatment, and IOP, pupillary diameter, conjunctival hyperemia, and blepharospasm were measured 0, 1, 6, and 12 hours after the first 4 treatments and 0 and 12 hours after the final 4 treatments. Measurements continued twice a day for 5 days after treatment was discontinued. Aqueous flare was measured once daily during and for 5 days after the treatment period. RESULTS: Intraocular pressure and pupillary diameter were significantly decreased in the treated eye of dogs, compared with the control eye. Mild conjunctival hyperemia was also detected, but severity did not differ significantly between eyes. Blepharospasm and aqueous flare were not detected in either eye. Intraocular pressure in cats was not significantly affected by treatment with latanoprost. However, pupillary diameter was significantly decreased in the treated eye, compared with the control eye. Conjunctival hyperemia, aqueous flare, and blepharospasm were not detected in either eye. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily topical ocular administration of latanoprost solution (0.005%) reduced IOP in healthy dogs without inducing adverse effects but did not affect IOP in healthy cats. Latanoprost may be useful for treating glaucoma in dogs.     

Effect of Clostridium perfringens epsilon toxin on the blood brain barrier of mice.

It was shown that Clostridium perfringens epsilon toxin has the effect of allowing the passage of 125I polyvinyl-pyrrolidone and 125I human serum albumin into mouse brain. These substances did not enter the brains of normal control mice. The passage of albumin into the brains of mice poisoned with epsilon toxin was extremely rapid. When large doses of toxin (+/-4 000 MLD) were given death ensued within 2-3 min at which stage 1,5% of the injected albumin had already entered the brain. In cases where smaller doses were given and the time interval between injection and death was longer the figure was increased to 2-2 1/2% of the injected plasma albumin.     

Xerostomia, xerophthalmia, and plasmacytic infiltrates of the salivary glands (Sjögren's-like syndrome) in a cat

A 2.5-year-old domestic shorthair cat was evaluated because of dysphagia and weight loss of 4 weeks' duration. MIld blepharospasm and conjunctival hyperemia were evident in both eyes, oral mucous membranes were tacky on palpation, and salivary glands were enlarged. Results of a Schirmer tear test were 0 mm/min for both eyes. Administration of atropine did not cause salivation or caused secretion fo thick rope-like saliva. Examination of biopsy specimens of salivary glands revealed a plasmacytic infiltrate. Sj?gren's syndrome (SS) was diagnosed. Oral administration of prednisone was instituted but was discontinued after a minimal positive response was evident 6 weeks after initiation of treatment. Palliative treatment with a 6% solution of pilocarpine 4 to 5 times/d, cyclosporine, hylan A, and neomycin-polymyxin-bacitracin ophthalmic ointment resulted in clinical improvement in the cat. Although reported rarely in animals, SS may be more common than currently is recognized. Most treatment regimens for SS are aimed at alleviating clinical signs.     

Effect of T-2 toxin on brain biogenic monoamines in rats and chickens.

Two experiments were conducted to determine the effect of T-2 toxin on brain biogenic monoamines and their metabolites. Male rats (180 g) and cockerels (28 day, 300 g) were orally dosed with T-2 toxin at 2.5 mg kg-1 body weight. In the first experiment, whole brains were collected 2, 6, 12, 24 and 48 h postdosing and analyzed for monoamines by high performance liquid chromatography with electro-chemical detection. T-2 toxin did not influence whole brain concentrations of monoamines in either species. In the second experiment, brains were collected 24 h postdosing, dissected into five brain regions, and analyzed for monoamines. T-2 toxin treatment resulted in increased serotonin and 5-hydroxy-3-indoleacetic acid in all brain regions of the rat. However, this was not seen in poultry where T-2 toxin treatment resulted in an increase in 5-hydroxy-3-indoleacetic acid, no alteration in serotonin concentration and a decrease in regional norepinephrine and dopamine concentrations. These results suggest that T-2 toxin influences brain biogenic amine metabolism and that there is an intraspecies difference in the central effects of this mycotoxin.     

Pyridoxine (a vitamin B6) and its derivative pyridoxal as treatment for Albizia versicolor poisoning in guinea-pigs

In the course of three experiments it was established that all the toxic effects of a lethal dose of Albizia versicolor pods (greater than 4.5 g/kg) in guinea-pigs could be countered by concurrent subcutaneous injection of pyridoxine (10 mg/kg). This treatment was also successful once severe symptoms had set in. Pyridoxal, on the other hand, was found to be ineffective as a therapeutic agent. The fact that pyridoxal does not counter the action of the toxin indicates an atypical site of action by the toxin as regards the normal pathways which require vitamin B6 as a co-factor.     

The distribution and density of Clostridium difficile toxin receptors on the intestinal mucosa of neonatal pigs

Clostridium difficile is an enteric pathogen affecting a variety of mammals, but it has only recently been diagnosed as a cause of neonatal typhlocolitis in pigs. The most important virulence factors of C. difficile are 2 large exotoxins, toxin A (TcdA) and toxin B (TcdB). TcdA is a potent enterotoxin with effects on host tissues that are dependent upon receptor-mediated endocytosis of the intact toxin. TcdB is an effective cytotoxin, but it apparently does not bind receptors on intact mucosal epithelium. TcdB is much less toxic in vivo unless there is underlying damage to the mucosa, and it is not essential for the virulence of C. difficile. One hypothesis to explain the resistance of most species as neonates (e.g., humans and hamsters) is that they may lack significant numbers of TcdA receptors. The susceptibility of neonatal pigs suggests cells of the gastrointestinal mucosa express sufficient numbers of toxin receptors for lesion development. Immunohistochemical (IHC) assays documented specific binding of TcdA, but not TcdB, to the epithelium of the small and large intestine. The carbohydrate Galalpha1-3beta1-4GlcNAc-R has been described as an important receptor for TcdA. However, IHC indicated a distribution on cell surfaces much different from that of TcdA binding, suggesting a specific interaction of toxin with an alternative receptor.     

Fatal Clostridium botulinum toxicosis in eleven Holstein cattle fed round bale barley haylage.

Twenty-two lactating Holstein cattle in Tennessee had clinical signs of intoxication with preformed Clostridium botulinum toxin. These signs included weakness, paralysis of the tongue and chest muscles, abdominal breathing, and, in 11 of the 22 cows, death. Differential diagnoses included hypocalcemia, hypomagnesemia, carbohydrate overload, and several toxicoses including mycotoxin, lead, nitrate, organophosphate, atropine or atropine-like alkaloid, and botulism. A diagnosis of botulism by the ingestion of preformed C. botulinum type B toxin was made by eliminating these other diseases, by finding C. botulinum type B spores in 3 bales of round bale barley haylage fed to these cattle, and by isolating preformed type B toxin from 1 of the 3 bales. Confirmation of the toxin type was made by demonstrating mouse lethality by intraperitoneal injection of specimen extracts with neutralization by C. botulinum type B antitoxin. The haylage, harvested green and encased in black plastic bags to facilitate fermentation, was presumably contaminated by the botulinum toxin when fermentation failed to produce enough acid to lower the pH to 4.5, the pH below which C. botulinum growth is inhibited. Farmers and ranchers who use round hay balers to produce haylage should be alert to this potential problem.     

The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig

T-2 toxin is known to be one of the most toxic trichothecene mycotoxins. Exposure to T-2 toxin induces many hematologic and immunotoxic disorders and is involved in immuno-modulation of the innate immune response. The objective of this work was to evaluate the effects of T-2 toxin on the activation of macrophages by different agonists of Toll-like receptors (TLR) using an in vitro model of primary porcine alveolar macrophages (PAM). Cytotoxic effects of T-2 toxin on PAM were first evaluated. An IC₅₀ of 19.47 ± 0.9753 nM was determined for the cytotoxicity of T-2 toxin. A working concentration of 3 nM of T-2 toxin was chosen to test the effect of T-2 toxin on TLR activation; this dose was not cytotoxic and did not induce apoptosis as demonstrated by Annexin/PI staining. A pre-exposure of macrophages to 3 nM of T-2 toxin decreased the production of inflammatory mediators (IL-1 beta, TNF-alpha, nitric oxide) in response to LPS and FSL1, TLR4 and TLR2/6 agonists respectively. The decrease of the pro-inflammatory response is associated with a decrease of TLR mRNA expression. By contrast, the activation of TLR7 by ssRNA was not modulated by T-2 toxin pre-treatment. In conclusion, our results suggest that ingestion of low concentrations of T-2 toxin affects the TLR activation by decreasing pattern recognition of pathogens and thus interferes with initiation of inflammatory immune response against bacteria and viruses. Consequently, mycotoxins could increase the susceptibility of humans and animals to infectious diseases.     

Pathologic, hematologic, and serologic changes in rabbits given T-2 mycotoxin orally and exposed to aerosols of Aspergillus fumigatus conidia

The influence of immunosuppression by T-2 mycotoxin on the fungal disease aspergillosis was investigated in rabbits. Four groups of rabbits (groups 1A, 1B, 3A, and 3B) were given 0.5 mg of T-2 toxin/kg of body weight/day, PO; in addition, rabbits of groups 3A and 3B were exposed to aerosols of Aspergillus fumigatus conidia from days 7 through 16. Rabbits of groups 2A and 2B were exposed to A fumigatus aerosols, but were not given T-2 toxin, and rabbits of group 0 served as controls. Two rabbits of group 1A, 1 rabbit of group 1B, and 1 rabbit of group 3A died before scheduled necropsy. Rabbits of groups 1A, 2A, and 3A were killed and necropsied on day 17, and the remaining rabbits (groups 0, 1B, 2B, and 3B) were killed and necropsied on day 28. Changes caused by T-2 toxin included leukopenia, marginal anemia, and increased number of and morphologic changes in nucleated erythrocytes by day 21, followed by a regenerative hematologic response. Serum alkaline phosphatase and sorbitol dehydrogenase activities and antibody response to A fumigatus (as measured by an indirect hemagglutination test) were decreased by T-2 toxin ingestion. Rabbits with aspergillosis had leukocytosis, increased PCV, and increased antibody response to A fumigatus. Histologic lesions consisting of centrilobular hepatocellular swelling, portal and periportal fibrosis, and lymphocyte necrosis and/or depletion within secondary lymphoid tissue were observed in most rabbits treated with T-2 toxin. Normal defense mechanisms against A fumigatus infection were compromised by T-2 treatment, as evidenced by the severity and extent of lung lesions, greater number of hyphal elements observed, and greater number of colonies of A fumigatus isolated from rabbits of groups 3A and 3B. There were no significant changes in group-0 rabbits.     

Isolation of exfoliative toxin from Staphylococcus hyicus subsp. hyicus and its exfoliative activity in the piglet

Exfoliative toxin was isolated from the sterile cell-free filtrate of 24 h culture of Staphylococcus hyicus subsp. hyicus strain P-1. The partial purification of exfoliative toxin produced by S. hyicus (shET) was performed by precipitation with 50-80% saturated ammonium sulfate, gel filtration on a Sephadex G-75 column and column chromatography on DEAE-cellulose. Partially purified shET (pp-shET) caused exfoliation in piglets at 8 to 12 h after intradermal or subcutaneous injection. However, heat-treated pp-shET did not cause exfoliation in piglets for up to 24 h after injection. On histopathological examination of the skin at 12 h after injection of pp-shET, an intraepidermal cleavage plane was shown between the stratum corneum and stratum granulosum and at the stratum granulosum.     

Brain and ocular metastases from a transmissible venereal tumour in a dog

A five-year-old crossbred dog was referred with rapidly growing masses over its penis and right popliteal lymph node. The dog had severe blepharospasm, congestion of episcleral vessels and rubeosis iridis of the left eye. A presumptive diagnosis of transmissible venereal tumour (TVT) and iridocyclitis was made based on the results of fine needle aspiration. Chemotherapy with vincristine and prednisolone was initiated and after four months the dog made a complete recovery. However, the dog subsequently relapsed, showing miosis, blepharospasm and a well defined mass within the anterior chamber of the left eye. In addition, the dog exhibited generalised 'grand mal' type seizures. Computed tomographic (CT) examination of the brain revealed two distinct masses in the left frontal lobe. Because of the poor prognosis, the owners elected to have the dog euthanased. On histopathology, metastases of TVT in the left eye and left cerebral hemisphere were found, showing no specific staining for CD3, immunoglobulin (Ig) G, IgM and lambda light chains. It was therefore concluded that the tumour growth was progressive, and that there was an absence of local humoral immune response against TVT in this case.     

Use of collagen shields for treatment of chronic bilateral corneal ulcers in a pet rabbit

A four-year-old, 1·3-kg entire male Holland Lop pet rabbit (Oryctolagus cuniculus) was presented with a two-day history of bilateral epiphora and blepharospasm. Fluorescein staining revealed bilateral medio-ventral corneal ulceration. Initial topical treatment included ophthalmic broad-spectrum antibiotics and artificial tear solutions. Over a six-month period, antibiotics were changed based on corneal culture and sensitivity test results, and periodic corneal debridement was performed. With little to no improvement, and recurrence of the previous clinical signs, surgical intervention was considered but withheld because of individual pet consideration and owner's reluctance. Hydrophilic contact lenses were placed for corneal support but failed and caused a severe ocular response. Corneal collagen shields were placed bilaterally in order to promote corneal healing. Recheck examination performed seven days after placement revealed complete resolution of the ulcer in one eye and major reduction of the corneal ulcer in the contra-lateral eye.     

Intraocular nematodiasis caused by Parelaphostrongylus tenuis in an eland antelope (Taurotragus oryx).

A 10-mo-old female eland (Taurotragus oryx) at the Wilds exhibited recalcitrant, progressive unilateral uveitis for a 5-wk period, despite constant medical treatment. Unilateral enucleation was performed because of blindness and animal discomfort evidenced by continuous blepharospasm. Histopathologic examination of the eye demonstrated intraocular larvae morphologically consistent with Parelaphostrongylus tenuis, the first known case of intraocular P. tenuis migration. This animal subsequently was euthanatized because of severe, nonresponsive neurologic signs associated with P. tenuis infection.