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Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets. R6 showed faster replication and pathogenicity than R7 in vitro and in mice. Subsequently, R6 was selected for the fitness comparison with the F strain in ferrets. Ferrets infected with the F virus showed more severe clinical signs, histopathological lung lesions, and viral quantification when compared to OR R6-infected animals. More importantly, differential viral kinetics correlated with differential pro-inflammatory host immune responses in the lungs of infected ferrets, where OR-infected animals developed a protective higher expression of type I IFN and Retinoid acid Inducible Gene I (RIG-I) genes early after infection, resulting in the development of milder disease. These results suggest the presence of early specific viral-host immune interactions relevant in the development of influenza-associated lung pathology., This work was funded by the coordinated project RTA 2011-00111-C03 of the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), by Instituto de Salud Carlos III (“Programa especial de investigación sobre la gripe pandémica” GR09/0023, GR09/0040, GR09/0039), and by the Servei de Diagnòstic de Patologia Veterinària (SDPV) of the Universitat Autònoma de Barcelona. This work was also partially funded by the CERCA program from Generalitat de Catalunya.

A 10-year-old, intact, captive-born female Mexican black kingsnake ( Lampropeltis getula nigrita ) was presented with a 1-week history of caudal coelomic distention. On physical examination a 5cm in length, soft nonmobile mass was identified in the caudal third of the coelomic cavity, 4cm cranially to the cloaca. Survey radiographic images revealed an increased soft tissue opacity within the affected area with variable sized, irregular mineralized structures. An intracloacal contrast study showed contrast retention in the cloaca. The retention of contrast within the cloaca was compatible with the presence of a mass compressing the rectum. An ultrasound evaluation confirmed a 2 × 3cm, oval, well-defined mass with an echogenic capsule. Computed tomographic imaging revealed a heterogeneous mass with some mineral areas with irregular shape and size. The mass was excised and the tissue submitted for histopathology and culture. The histopathological and microbiological diagnosis of the mass was purulent interstitial nephritis with presence of multiple histiocytic granulomas that contained intralesional bacteria ( Morganella morganni ). The animal responded well to the surgical removal of the mass and subsequent medical treatment.

The purpose of this report is to describe 2 cases of chylous ascites (CA) in ferrets. In the first patient, CA was likely secondary to an obstruction of lymphatic drainage due to lymphoma; and in the second patient, CA developed as a postoperative complication of adrenal carcinoma with multiple metastases. In both cases, CA was diagnosed based on the concentration of triglycerides and cholesterol in the abdominal fluid. Medical treatment resulted in partial remission of the CA in the first case; however, the patient suffered an acute death approximately 3 weeks following its initial presenation. In the second patient, multiple abdominocenteses were required to relieve abdominal discomfort and dyspnea. Five days after the adrenal surgery the ferret developed chylothorax and septic peritonitis, and due to its deteriorating condition was humanely euthanatized. Although the final outcomes in the 2 ferret cases were disappointing, advanced neoplastic disease, usually associated with a poor prognosis, was considered the underlying cause of CA in both patients. More studies are required in ferrets diagnosed with CA to determine proper nutritional and medical management, diagnostic tests, and surgical options. Unfortunately, there is little information describing CA in ferrets and the veterinary medical literature as a whole.

OBJECTIVE To evaluate the usefulness of excretory urography performed during radiography (REU) and CT (CTEU) in healthy rabbits, determine timings of urogram phases, and compare sensitivities of REU and CTEU for detection of these phases. ANIMALS 13 New Zealand White rabbits (Oryctolagus cuniculus). PROCEDURES Rabbits were screened for signs of systemic and urinary tract disease. An REU examination of each was performed, followed ≥ 5 days later by a CTEU examination. Contrast images from each modality were evaluated for quality of opacification and intervals between initiation of contrast medium administration and detection of various urogram phases. RESULTS Excretory urograms of excellent diagnostic quality were achieved with both imaging modalities. For all rabbits, the nephrographic phase of the urogram appeared in the first postcontrast REU image (obtained between 34 and 40 seconds after initiation of contrast medium administration) and at a median interval of 20 seconds in CTEU images. The pyelographic phase began at a median interval of 1.63 minutes with both imaging modalities. Contrast medium was visible within the urinary bladder at a median interval of 2.20 minutes. Median interval to the point at which the nephrogram and pyelogram were no longer visible in REU images was 8 hours and 2.67 hours, respectively. The CTEU technique was better than the REU technique for evaluating renal parenchyma. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that REU and, particularly, CTEU may be valuable tools for the diagnosis of renal and urinary tract disease in rabbits; however, additional evaluation in diseased rabbits is required.

An 8-year-old spayed female domestic ferret ( Mustela putorius furo ) was presented for evaluation of anal prolapse and bilateral enlarged anal sacs. A lobulated mass in the right perianal area was detected during the physical examination. Results of diagnostic blood testing confirmed decreased glucose, potassium, and phosphorus concentrations, and increased total and ionized calcium concentrations. Complete resection of the mass was not possible owing to its nearness to the rectum and the ventral aspect of the tail. Imprint cytological preparations obtained intraoperatively were compatible with anal sac adenocarcinoma, which was confirmed by histopathologic evaluation of submitted tissue samples of the mass. Routine staging showed iliac lymph node and presumptive lung metastases; therefore, chemotherapy was initiated. This report describes a confirmed case of anal sac adenocarcinoma with metastases and hypercalcemia, managed with surgery and chemotherapy for 13 months after the patient׳s initial presentation and diagnosis.

A 1-month-old, intact female domestic rabbit was presented with a history of acute right hind limb lameness due to a traumatic injury. Physical examination revealed right elbow luxation, varus deviation, and a reduction in antebrachial length. Radiographic imaging of the affected limb revealed lateral right elbow luxation, radial agenesis, right first digit agenesis, and malformation of the right carpal bones and sternum. The patient’s diagnosis based on the presenting clinical signs and radiographic evaluation was determined to be right preaxial longitudinal intercalary radial hemimelia, partial adactyly, and multiple bone malformations. Hemimelia is the most common congenital limb malformation in domestic animals. Clinical signs can be variable, ranging from subclinical to severe locomotion problems. Although it has not been reported in pet rabbits, hemimelia should be considered in the young of this species that present with lameness. Early diagnosis is essential to avoid muscle atrophy and worsening of bone deformities, which may adversely affect quality of life of the patient.

A 6-year-old female domestic ferret presented with a 3-day history of lethargy and anorexia. Clinical examination revealed severe jaundice, painful abdominal palpation, and a mass in the left cranial abdomen. Blood diagnostic tests of the patient revealed a regenerative anemia, severe neutrophilic and monocytic leukoctytosis, increased alanine aminotransferase and total bilirubin, and decreased albumin and glucose concentrations. Liver lobe torsion (LLT) was identified through radiographic and ultrasonographic imaging. Postmortem examination confirmed a left lateral liver lobe torsion, and a generalized hepatic lipidosis. LLT is a rare condition with few reported cases in veterinary medicine. LLT should be considered as a differential disease diagnosis in ferrets presenting with acute abdomen.

A 2-year-old female, spur-thighed tortoise ( Testudo graeca) was presented with poor body condition (1/5) and weakness. Fecal analysis revealed large numbers of oxyurid-like eggs, and radiographs were compatible with gastrointestinal obstruction. Despite supportive medical treatment, the animal died. At gross examination, an intestinal obstruction was confirmed. Histopathology revealed severe hyperplastic esophagitis and stomatitis with marked epithelial cytomegaly and enormous basophilic intranuclear inclusion bodies. Electron microscopy examination revealed a large number of 60–80 nm, nonenveloped, icosahedral virions arranged in crystalline arrays within nuclear inclusions of esophageal epithelial cells, morphologically compatible with adenovirus-like particles. PCR for virus identification was performed with DNA extracted from formalin-fixed, paraffin-embedded tissues. A nested, consensus pan-adenovirus PCR and sequencing analysis showed a novel adenovirus. According to phylogenetic calculations, it clustered to genus Atadenovirus in contrast with all other chelonian adenoviruses described to date. The present report details the pathologic findings associated with an adenovirus infection restricted to the upper digestive tract.

An 8-month-old neutered male ferret was presented for vaccination and preventive treatment for adrenal gland disease. Abdominal ultrasound revealed severe bilateral hydronephrosis and hydroureter. Excretory urography and negative contrast cystography showed bilateral ureterovesical junction stenosis. Positive retrograde cystography demonstrated right ureteral reflux. A subcutaneous ureteral bypass was placed in the left kidney; however, it had to be removed 3 months later due to an obstruction and persistent urinary tract infection. Bilateral ureteroneocystotomy was performed. Although congenital strictures are uncommon in veterinary patients, they should be included in the differential diagnosis in ferrets presenting with hydronephrosis and hydroureter of undetermined cause.

A 5-month-old African grey parrot (Psittacus erithacus) was examined after 3 weeks of weakness, ataxia, mental depression, and seizures. Results of a complete blood cell count and plasma biochemical analysis were unremarkable. Magnetic resonance imaging revealed a severe bilateral hydrocephalus. The bird failed to improve with supportive care, and the owner requested euthanasia. Necropsy findings were severe bilateral hydrocephalus with no evidence of cerebrospinal fluid obstruction. Histologic examination of the brain revealed microspongiosis, edema, gliosis, and neuronal chromatolysis of surrounding periventricular tissue. Aquaporins (AQP) and astrocytes were examined to elucidate the participation of these water channel proteins and glial cells in the pathophysiology and resolution of hydrocephalus. Results showed AQP4 and glial fibrillary acidic protein were overexpressed, especially near the ventricles, but expression of AQP1 was decreased. This is the first report, to our knowledge, of AQP immunolabeling in hydrocephalus in avain species.

A 3-month-old intact female ferret (Mustela putorius furo) was presented with a 2-month history of ataxia. On physical examination, the ferret had difficulty standing upright. During the neurologic examination, the patient had a left head tilt and positional strabismus, circled to the left, and was ataxic. Results of the complete blood count were consistent with a mild normocytic normochromic anemia. Initial treatment was supportive. Magnetic resonance imaging was performed and revealed an asymmetry of the inner ears. A brainstem auditory evoked response test was also performed. History, clinical signs, and diagnostic test results indicated that the ferret was suffering from congenital peripheral vestibular syndrome and left-sided deafness. Congenital disease should be considered in the differential diagnosis of young ferrets with peripheral vestibular syndrome. Supportive care and physiotherapy can improve balance and motor function, leading to an acceptable quality of life.

Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3. Electronic supplementary material The online version of this article (doi:10.1186/s13567-016-0395-0) contains supplementary material, which is available to authorized users.

An 8-month-old neutered male ferret was presented for vaccination and preventive treatment for adrenal gland disease. Abdominal ultrasound revealed severe bilateral hydronephrosis and hydroureter. Excretory urography and negative contrast cystography showed bilateral ureterovesical junction stenosis. Positive retrograde cystography demonstrated right ureteral reflux. A subcutaneous ureteral bypass was placed in the left kidney; however, it had to be removed 3 months later due to an obstruction and persistent urinary tract infection. Bilateral ureteroneocystotomy was performed. Although congenital strictures are uncommon in veterinary patients, they should be included in the differential diagnosis in ferrets presenting with hydronephrosis and hydroureter of undetermined cause.

A 3-year-old female African hedgehog ( Atelerix albiventris ) was presented with a progressive history of depression, hyporexia, weight loss, and severe ataxia of the pelvic limbs. The diagnostic blood test results were nonspecific and whole-body radiographs revealed an enlarged spleen. Ultrasonographic images showed splenomegaly with multiple hypoechoic nodules. Based on imaging, an initial diagnosis of a degenerative, vascular, or neoplastic disease was made. Because of a poor prognosis, the owners requested euthanasia and allowed for a pathologic examination of the hedgehog. Histopathologic review of the tissues confirmed that the animal had lymphoma. Lesions were multicentric and involved the spleen, mediastinal lymph node, and central nervous system. To the authors' knowledge, this is the first report of splenic lymphoma with cerebellar involvement in an African hedgehog.

A 4-year-old, spayed female ferret ( Mustela putorius furo ) presented for alopecia, pruritus, and swollen vulva. The ferret was treated for a suspected ovarian remnant at 1.5 years of age. On presentation, the physical examination revealed a large, hard, nonpainful caudal intraabdominal mass. The results of diagnostic blood tests and radiographic images were nonspecific relative to determining a definitive diagnosis. An exploratory laparotomy was performed to remove the mass. Histopathology identified the mass as a thecoma. Although neoplasia is common in ferrets, reproductive system malignancies are underreported in this species because most are acquired as gonadectomized pets. The following article describes a case of a sex hormone–producing thecoma in a female ferret with alopecia and swollen vulva.

A 2-year-old spayed female ferret ( Mustela putorius furo ) was presented with a 2-day history of ambulatory paraparesis of the hind limbs. On physical examination a mass was palpated in the cranial abdominal region, caudal to the stomach. A complete blood cell count revealed a normocytic normochromic anemia and reactive lymphocytes. A hypoechoic abdominal mass was observed during an ultrasound examination of the abdomen. An exploratory laparotomy was recommended and performed during which a pyramidal mass resembling a lobe of fatty liver tissue, plus omental torsion, was removed. The histopathologic diagnosis of the surgically removed mass was splenosis. The abdominal pain and ambulatory paraparesis resolved after surgery, which suggests that the paraparesis was due to pain. The findings in this report indicate that splenosis should be included as a differential diagnosis when a ferret presents with an abdominal mass and acute abdominal pain.

Bilateral exudative chorioretinitis was diagnosed in an 18-month-old male neutered ferret (Mustela putorius furo) with a generalized Cryptococcus gattii infection confirmed by PCR. The animal was referred to the Ophthalmology Service of the Autonomous University of Barcelona (VTH-UAB) for acute onset blindness. Complete ophthalmic examination revealed absent menace response and dazzle reflex in both eyes (OU), as well as subretinal edema located in the tapetal fundus. At that time, the clinical ophthalmologic diagnosis was bilateral exudative chorioretinitis. Treatment with prednisone (0.5 mg/kg PO q24 h) was instituted in addition to the ongoing treatment with fluconazole (10 mg/kg PO q24 h). The following rechecks revealed secondary cataracts with subsequent lens subluxation and panretinal degeneration OU. Despite being blind and the poor prognosis of disseminate cryptococcosis, the patient remained active and in good body condition during 6 months after the initial diagnosis. At that time, the ferret showed ataxia, incontinence, and generalized pain. A magnetic resonance imaging study revealed a mass affecting the spine. The owners declined further investigations and the ferret was humanely euthanized. The postmortem histopathology confirmed the initial diagnosis of cryptococcosis and the presence of intraretinal Cryptococcus spp. To the authors' knowledge, this is the first report of Cryptococcus spp. induced exudative chorioretinitis in a ferret.

Background: Protein electrophoresis is widely applied in veterinary medicine, but is not used often in reptiles, in part because of lack of reference values. Objective: The goals of this study were to compare plasma protein profiles obtained by cellulose acetate electrophoresis (CAE) and agarose gel electrophoresis (AGE), measure precision and examine interference by sample hemolysis, and establish preliminary reference intervals for 2 reptile species. Methods: Heparinized plasma samples from healthy and diseased adult female Iguana iguana (n=40) and Trachemys scripta (n=60) were analyzed by CAE and AGE. Total protein concentration was measured by the biuret method. Electrophoresis results were compared using Bland–Altman plots and Passing–Bablok regression analysis. Precision and the effects of sample hemolysis were determined. Results from clinically healthy animals were used to determine reference intervals. Results: Five protein fractions were identified in both species, with bisalbuminemia observed in 23/40 iguanas. High correlation was observed between the 2 methods for all fractions, with few proportional and systematic errors. Coefficients of variation were lower using AGE vs CAE and for I. iguana vs T. scripta. Two additional bands were observed in hemolyzed samples from T. scripta; 1 additional band was observed for I. iguana. Minimum and maximum values were reported for healthy I. iguana (n=14) and T. scripta (n=22). Conclusions: Although both methods are acceptable, the performance of AGE was slightly better than that of CAE for analysis of plasma from reptiles. Furthermore, reptile electrophoretic patterns should be interpreted based on the method used, the species analyzed, and the quality of the plasma sample.

A 1-year-old male dwarf hamster ( Phodopus sungorus ) with an inflammation of 7 days' duration in the right ear was examined. Abnormalities noted on physical examination were limited to the right ear and an anal mass. The right ear showed swollen skin and a yellowish secretion. The pinna presented scabs and ulcers, probably secondary to the scratching. Cytological examination of the secretion revealed rod-shaped bacteria and neutrophils. The anal mass was a freely movable nodule 1 mm in diameter attached to the anal skin. Initial treatment consisted of antibiotics and antiinflammatory drugs. After an incomplete response to the treatment, surgery was proposed. The surgical procedures consisted of right ear pinna and vertical canal ablation, and excision of the anal mass. The animal recovered uneventfully. All the samples were submitted for histologic examination. The diagnosis was aural squamous cell carcinoma (SCC) and anal papilloma. Although many neoplasias have been described in laboratory rodents, cutaneous SCC is underreported in rodents kept as pets, especially in hamsters. The case here describes an aural SCC that caused a nonresponsive otitis externa in a dwarf hamster. The tumor was successfully removed and the otitis resolved completely. To the authors' knowledge, this is the first report of ear SCC resolved after surgery in a dwarf hamster.

A case of a dwarf hamster with two progressively growing nodules on the right fore limb is described. These were excised following ineffective medical treatment and were submitted for histopathological examination, which revealed bacterial pseudomycetoma in both nodules. To the authors' knowledge this is the first reported case of bacterial pseudomycetoma in a dwarf hamster.

The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts’ capacities to mount efficient immune responses to control viral infection of the lung. Electronic supplementary material The online version of this article (doi:10.1186/s13567-014-0085-8) contains supplementary material, which is available to authorized users.

Case Description—A 5-year-old 2.23-kg (4.91-lb) spayed female Lop rabbit (Oryctolagus cuniculus) was evaluated because of a history of lethargy, polyuria, and polydipsia of 1 month's duration. The referring veterinarian made a presumptive diagnosis of hypercalcemia of unknown etiology on the basis of a plasma total calcium concentration of 14.0 mg/dL. Clinical Findings—Physical examination findings were unremarkable. Hematologic and plasma biochemical analysis revealed nonregenerative, normocytic, normochromic anemia (PCV, 28%) with heteropenia (23%; 1,334 heterophils/mL) and a total plasma calcium concentration of 16 mg/dL. Radiographic and ultrasonographic examination revealed radiodense and hyperechoic structures in both renal pelves and right unilateral nephrolithiasis. Treatment and Outcome—Nephrotomy was performed via laparotomy with a right lateral approach. A nephrolith composed of calcium carbonate and carbonate apatite was removed from the right renal pelvis. The rabbit's plasma tested positive for antibodies against Encephalitozoon cuniculi by means of an indirect immunofluorescence assay, and fenbendazole (20 mg/kg [9.1 mg/lb], PO, q 24 h) was administered for 28 days. Although plasma calcium concentration was not substantially decreased after treatment (values were 14.1 and 15.1 mg/dL 1 week and 3 months after surgery, respectively), the patient did not have clinical signs of hypercalcemia and died of unrelated causes approximately 1 year after surgery. Clinical Relevance—To the authors' knowledge, this is the first report of a nephrotomy performed in a rabbit via a lateral abdominal approach. This approach allowed easy location of the kidney and also reduced manipulation, thus decreasing the risk of damaging the abdominal viscera and potentially decreasing postoperative pain.

Bilateral exudative chorioretinitis was diagnosed in an 18-month-old male neutered ferret (Mustela putorius furo) with a generalized Cryptococcus gattii infection confirmed by PCR. The animal was referred to the Ophthalmology Service of the Autonomous University of Barcelona (VTH-UAB) for acute onset blindness. Complete ophthalmic examination revealed absent menace response and dazzle reflex in both eyes (OU), as well as subretinal edema located in the tapetal fundus. At that time, the clinical ophthalmologic diagnosis was bilateral exudative chorioretinitis. Treatment with prednisone (0.5 mg/kg PO q24 h) was instituted in addition to the ongoing treatment with fluconazole (10 mg/kg PO q24 h). The following rechecks revealed secondary cataracts with subsequent lens subluxation and panretinal degeneration OU. Despite being blind and the poor prognosis of disseminate cryptococcosis, the patient remained active and in good body condition during 6 months after the initial diagnosis. At that time, the ferret showed ataxia, incontinence, and generalized pain. A magnetic resonance imaging study revealed a mass affecting the spine. The owners declined further investigations and the ferret was humanely euthanized. The postmortem histopathology confirmed the initial diagnosis of cryptococcosis and the presence of intraretinal Cryptococcus spp. To the authors' knowledge, this is the first report of Cryptococcus spp. induced exudative chorioretinitis in a ferret.

A 61-year-old female Mediterranean tortoise (Testudo hermannii) presented after 1 week of tetraparesis. Coelomic ultrasonography revealed free fluid and an ovarian mass with multiple follicles. Blood analysis suggested renal failure. After initial medical treatment for kidney disease, the tortoise seemed to improve clinically, but the animal died 2 months later. Necropsy and histopathology revealed an ovarian teratoma. To our knowledge, this is the first reported case of a teratoma in tortoise gonadal tissue.

Sera of 30 patients with primary biliary cirrhosis (PBC) and 72 normal subjects matched for age and sex were examined for the presence of lymphocytotoxic antibodies (LCAs) against B and T cells at 4 degrees C and 37 degrees C. Patients were prospectively screened for: Sjögren's syndrome, scleroderma, Hashimoto's thyroiditis, and rheumatoid arthritis, in which LCAs have been described. Seventeen patients with PBC (56.6%) had LCAs against B cells as compared with only 11 of the 72 normal subjects (P less than 0.001). Five PBC patients (16.6%) also reacted against T cells as compared with none in control group (P less than 0.01). Clinical and biochemical features and the histological stage of PBC were similar in patients with and without LCA. Sjögren's syndrome was present in 13 patients--two with scleroderma and another with Hashimoto's thyroiditis. No patient had rheumatoid arthritis. The prevalence of LCAs was similar in PBC patients with or without autoimmune associated disease (54% vs 59%). We conclude that in PBC a high incidence of LCA is unrelated to the presence of an associated disease. LCA in PBC might be a nonspecific marker of an immune disorder.