Hypernatraemia in 39 hospitalised foals: clinical findings, primary diagnosis and outcome.

OBJECTIVE: To evaluate hypernatraemia in foals presenting as medical emergencies to an intensive care unit (ICU) to determine the prevalence, clinical findings, primary diagnosis and outcome. METHODS: Retrospective case study of records from Thoroughbred foals aged less than 3 months that presented to an ICU as medical emergencies in 2002-12. Data retrieved included signalment, clinical findings, laboratory results, primary diagnosis and outcome. Foals with hypernatraemia (serum sodium > 145 mmol/L) on admission laboratory data were identified and further evaluated. RESULTS: A total of 39 of 1718 foals (2.3%) were diagnosed with hypernatraemia; all foals were less than 7 days of age. The most common primary diagnoses in the foals with hypernatraemia were neonatal syndrome (19/39, 48.7%) and sepsis (15/39, 38.5%). Foals with hypernatraemia at presentation were more likely to die or be euthanased during their hospitalisation than foals with a normal serum sodium concentration on ICU admission (33.3% vs 16.1%; odds ratio, 2.3; 95% confidence interval, 1.2-4.6; P = 0.02). CONCLUSION: Admission hypernatraemia was an uncommon but important electrolyte abnormality in this population of hospitalised foals. Although the short-term outcome in survivors was most likely dependent on the underlying disease process, hypernatraemia was negatively associated with outcome in hospitalised foals.

Severe hyponatraemia in foals: clinical findings, primary diagnosis and outcome.

OBJECTIVE: To evaluate severe hyponatraemia in foals presenting as medical emergencies to an intensive care unit (ICU) in order to determine the prevalence, clinical findings, primary diagnosis and outcome. DESIGN: Retrospective case study of records from Thoroughbred foals aged less than 3 months presenting to an ICU as medical emergencies in 2002-12; foals with severe hyponatraemia (serum sodium <122 mmol/L) on admission laboratory data were identified. Data retrieved included signalment, clinical findings, laboratory results, primary diagnosis, treatment and outcome. RESULTS: Severe hyponatraemia was identified in 69/1718 Thoroughbred foals (4%) presenting to the ICU during the study period. Of the 69 foals, 11 (15.9%) presented with neurological signs attributable to hyponatraemic encephalopathy and 7 of these foals had seizures; other neurological signs included obtundation, ataxia and apparent blindness. The three most common primary diagnoses of the 69 foals with severe hyponatraemia were renal disease (18/69, 26.1%), enterocolitis (16/69, 23.2%) and uroperitoneum (15/69, 21.7%). Treatment was directed at the primary disease and correction of the hyponatraemia. A total of 50 of the 69 foals (72.5%) with severe hyponatraemia survived to hospital discharge and 38 of them (76%) survived at least 12 months following discharge. CONCLUSION: The prevalence of severe hyponatraemia in this study population was 4%. The majority of foals with severe hyponatraemia did not demonstrate direct clinical manifestations as a result of the low serum sodium concentration. The outcome of foals with severe hyponatraemia was mostly favourable.

Sequential L-lactate concentration in hospitalised equine neonates: A prospective multicentre study.

REASONS FOR PERFORMING STUDY: Evaluation of serial blood lactate concentrations [LAC] are of prognostic value for morbidity and mortality in critically ill human patients and neonatal foals, but have not been prospectively evaluated in a large multicentre study of critically ill neonatal foals. OBJECTIVES: To prospectively evaluate the prognostic value of sequential [LAC] analysis in critically ill neonatal foals with risk of mortality. STUDY DESIGN: Prospective, observational study. METHODS: Thirteen university and private equine referral hospitals enrolled 643 foals over the 2008 foaling season and [LAC] was measured at admission ([LAC]ADMIT ) and 24 ([LAC]24 ), 48 ([LAC]48 ), 72 ([LAC]72 ), 96 ([LAC]96 ) and 120 h ([LAC]120 ) after admission. [LAC] changes over time ([LAC]Δ) were calculated between sampling points. RESULTS: Nonsurvivors had significantly greater [LAC]ADMIT , [LAC]24 and [LAC]48 compared with surviving foals (P<0.001). In nonsurviving foals [LAC]Δ did not decrease over time while survivors showed significant positive [LAC]Δ between [LAC]ADM -24 and all other time periods (P<0.001). Logistic regression analysis showed that the odds of survival decreased for each 1 mmol/l [LAC] increase at all time points for all critically ill foals, independent of major final diagnoses as potential confounders. Septic foals had significantly greater [LAC] at all time points compared with nonseptic foals (P<0.001) and [LAC]Δ in septic foals was significantly more positive (suggesting better clearance of lactate from the blood) only at [LAC]ADM -24 and [LAC]72-96 (P<0.01), while in nonseptic foals [LAC]Δ was significantly positive between [LAC]ADM -24 compared with all other time periods (P<0.001). CONCLUSIONS: Blood lactate concentration is a strong, independent biomarker used to predict mortality in critically ill foals. Lactate metabolism is impaired in nonsurviving and septic foals and [LAC]Δ can be utilised to identify patients at high risk for mortality.

Equine multinodular pulmonary fibrosis in three horses in Australia.

BACKGROUND: Equine multinodular pulmonary fibrosis (EMPF) is a recently described form of interstitial pneumonia associated with the presence of equine herpesvirus type 5 (EHV-5). Since 2007, several case reports from America, Europe and the United Kingdom have further characterised the clinical presentation and laboratory findings of this disease. CASE REPORTS: Three Thoroughbred broodmares were diagnosed with EMPF. Diagnosis was based on lung histopathology and positive identification of EHV-5 using PCR DNA amplification. There was multiple organ involvement in all three cases, including identification of EHV-5 in hepatic tissue in one case. Two of the three horses died. Treatment with acyclovir was unsuccessful in one horse and one horse survived without antiviral or corticosteroid treatment. CONCLUSION: This case series is, to the authors' knowledge, the first report of EMPF in Australia and adds to the clinical description of the disease.

Case series of equine pituitary pars intermedia dysfunction in a tropical climate.

The clinical manifestations of equine pituitary pars intermedia dysfunction (PPID) in temperate climates are well described. The classic presentation is that of an older animal with hirsutism, laminitis, poor muscle tone, pendulous abdomen and weight loss. This case series highlights the additional clinical signs of anhidrosis and heat stress with secondary exercise intolerance that were seen as primary presenting problems in equids with PPID in the hot, humid conditions of a tropical climate. The clinical signs resolved with medical treatment for PPID.

Association of admission L-lactate concentration in hospitalised equine neonates with presenting complaint, periparturient events, clinical diagnosis and outcome: a prospective multicentre study.

REASONS FOR PERFORMING THE STUDY: Admission L-lactate concentration is a useful and commonly measured biomarker not previously prospectively evaluated in a large multicentre study of critically ill neonatal foals. OBJECTIVES: To evaluate overall outcome and the association of survival and L-lactate concentration at admission ([LAC]ADMIT) by periparturient history, presenting complaint and clinicians' major diagnosis for ill neonatal foals. METHODS: Thirteen university and private equine referral hospitals enrolled 643 foals over the 2008 foaling season. Case details, historical, clinical and clinicopathological data were entered into standardised spreadsheets then unified for analysis. RESULTS: Overall survival was 79% (505/643). Risk of nonsurvival increased with each 1 mmol/l increase in [LAC]ADMIT (odds ratio 1.14, P < 0.001). Mean arterial pressure had a small (r2 = 19.1) but significant (P < 0.001) association with [LAC]ADMIT. Foals experiencing known dystocia or premature placental separation had increased [LAC]ADMIT (P < 0.001). Single umbilical problems (excluding uroperitoneum), meconium impaction only and failure of passive transfer of immunity only had 100% survival. Six clinicians' major diagnoses had increased odds of nonsurvival for each 1 mmol/l increase in [LAC]ADMIT: 'sepsis'; 'unspecified enterocolitis'; 'unspecified colic'; 'unspecified trauma'; 'immune related (not failure of passive transfer of immunity)' and 'respiratory only'. CONCLUSIONS AND POTENTIAL RELEVANCE: Survival of critically ill foals is good but varies with peripartum history, presenting complaint and clinicians' major diagnosis. L-lactate concentration at admission proves its utility as a valuable prognostic biomarker in neonatal foals and its utility appears to vary with peripartum history and clinicians' major diagnosis.

Treatment with histamine-type 2 receptor antagonists and omeprazole increase the risk of diarrhoea in neonatal foals treated in intensive care units.

REASONS FOR PERFORMING STUDY: The use of anti-ulcer medication in the neonatal intensive care unit (ICU) is common due to the concern for development of catastrophic gastric ulcerdisease. In man, however, the use of acid-suppressive medication has been shown in some studies to be a substantial riskfactorfor the development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and neonatal sepsis. OBJECTIVE: The purpose of the study reported herein is to evaluate the influence of anti-ulcer medications on the development of diarrhoea in the neonatalfoal. HYPOTHESIS: The use of anti-ulcer medication does not alter the incidence of diarrhoea in foals treated in an ICU. METHODS: The records of 1710 foals from 6 different equine hospitals were examined and the use of anti-ulcer drugs was recorded. The presence of in-hospital acquired diarrhoea, CDAD, Clostridium perfringens-associated diarrhoea, neonatal sepsis and salmonellosis were documented. In addition, the presence of gastric ulceration, duration of hospital stay and short-term outcome were examined. RESULTS: The use of anti-ulcer medications increased the odds of in-hospital diarrhoea by 2.0 (95% CI 1.4-2.9; P < 0.0001), relative to the use of no anti-ulcer medication. There was no significant association of anti-ulcer medication with CDAD (P = 0.3189) (OR 2.0; 95% CI 0.4-9.5). Further, results indicated that decreased prevalence of gastric ulceration was not associated with use of anti-ulcer drugs among foals in the study for which these data were known (P = 0.5522). CONCLUSIONS: Use of anti-ulcer drugs increases the odds of developing diarrhoea, and may not reduce the incidence of gastric ulceration in hospitalised equine neonates. POTENTIAL RELEVANCE: The use of anti-ulcer drugs in neonatal foals being treated in a hospital setting should be carefully evaluated on an individual basis to determine if such use is warranted.

Methicillin-resistant Staphylococcus aureus in a population of horses in Australia.

OBJECTIVE: To evaluate if methicillin-resistant Staphylococcus aureus (MRSA) is present in the horse population in Australia. DESIGN: A two-part retrospective study of laboratory submissions of microbial culture results from horses. METHODS: Part A: medical records of 216 horses that had MRSA screening performed on nasal swabs collected over a 30-day period at admission to the Scone Equine Hospital Clovelly Intensive Care Unit were retrieved. Part B: laboratory records from 2004 to 2009 of culture submissions to the Scone Veterinary Laboratory were reviewed and cultures that grew MRSA were identified. The MRSA isolates from Parts A and B were genotyped over an 18-month period. RESULTS: MRSA screening of 216 horses identified eight (3.7%) positive samples. MRSA was isolated from cultures of 80 (0.002%) clinical bacteriology samples over a 6-year period. Genotypic analysis was performed on 36 isolates. All MRSA characterised had the same pulse field gel electrophoresis pattern (type 1), with eight closely related subtypes identified (subtypes A-F and H) and 66% of isolates classified as subtype D, which multilocus sequence and staphylococcal cassette chromosome mec typing analysis identified as ST612-MRSA-IVa, a clonal complex (CC) 8 S. aureus strain. Antimicrobial resistance to more than two classes of antimicrobials was common. CONCLUSIONS: MRSA was present in a population of horses in Australia. Genotypic analysis of the isolates identified the MRSA strain as CC8 S. aureus. Further research needs to be undertaken to evaluate MRSA infection and colonisation of horses and personnel in Australia.

Carriage of methicillin-resistant Staphylococcus aureus by veterinarians in Australia.

OBJECTIVE: To estimate the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA) among Australian veterinarians. METHODS: Individuals attending veterinary conferences in Australia in 2009 were recruited to provide nasal swabs and complete a questionnaire about their professional activities. Swabs were processed by standard methods for detecting MRSA and questionnaire responses were used to group veterinarians according to their areas of major work emphasis (species and practice type). Prevalence was estimated for each of these grouping and contingency tables and regression tree analysis used to explain the variation in MRSA carriage. RESULTS: Among the 771 respondents 'industry and government veterinarians' (controls) had the lowest prevalence of MRSA carriage at 0.9%. Veterinarians with horses as a major area of work emphasis had a prevalence of 11.8% (13-fold that of controls) and those whose only major emphasis was horses had a prevalence of 21.4% (23-fold that of controls). Veterinarians with dogs and cats as a major activity had a 4.9% prevalence (5-fold that of controls). Prevalence rates for other major activities (pigs, dairy and beef cattle, avian and wildlife) were also increased, but were estimated from smaller numbers of respondents. Regression tree analysis clearly isolated equine veterinarians and dog and cat practitioners as groups at increased risk of carriage of MRSA. CONCLUSION: Carriage of MRSA is a notable occupational health issue for veterinarians in clinical practice in Australia, particularly those who work with horses.

A multicenter retrospective study of 151 renal biopsies in horses.

BACKGROUND: Renal biopsies are uncommonly performed in horses and little is known about their diagnostic utility and associated complication rate. OBJECTIVE: To describe the techniques, the complication rate, risk factors, and histopathology results; as well as evaluate the safety and diagnostic utility of renal biopsy in the horse. ANIMALS: One hundred and forty-six horses from which 151 renal biopsies were obtained. Animals ranged in age from 48 hours to 30 years. METHODS: Multicenter retrospective study, with participation of 14 institutions (1983-2009). RESULTS: Renal biopsy in horses was associated with a similar rate of complications (11.3%) to that occurring in humans and companion animals. Complications were generally associated with hemorrhage or signs of colic, and required treatment in 3% of cases. Fatality rate was low (1/151; 0.7%). Biopsy specimens yielded sufficient tissue for a histopathologic diagnosis in most cases (94%) but diagnoses had only fair (72%) agreement with postmortem findings. Risk factors for complications included biopsy specimens of the left kidney (P = .030), a diagnosis of neoplasia (P = .004), and low urine specific gravity (P = .030). No association with complications was found for age, sex, breed, institution, presenting complaint, other initial clinicopathologic data, biopsy instrument, needle size, or use of ultrasonographic guidance. CONCLUSIONS AND CLINICAL IMPORTANCE: Renal biopsy in horses has low morbidity and results in a morphological histopathologic diagnosis in 94% of cases. However, this procedure might result in serious complications and should only be used when information obtained would be likely to impact decisions regarding patient management and prognosis.

Retrospective study of 108 foals with septic osteomyelitis.

OBJECTIVE: To determine the clinical characteristics, short-term outcome and future athletic performance of foals with septic osteomyelitis. DESIGN: Retrospective clinical study of 108 Thoroughbred foals with radiographic evidence of bone infection that were presented at the Scone Veterinary Hospital between August 1995 and December 2001. Medical records were reviewed and information concerning signalment, the clinical, laboratory and radiographic findings, treatment and outcome was obtained. Racing records were obtained and evaluated for surviving foals that had reached racing age. RESULTS: Mean age of foals at initial evaluation was 39 days (range 1-180 days); 21 foals had multiple radiographic bone lesions (19.4%), and 76 had concurrent septic arthritis (70.4%). The most frequently affected bones were the femur, tibia and distal phalanx. In total, 87 foals were discharged from the hospital (80.6%), 79 survived long-term to reach racing age and 52 raced (65.8%). Overall, 48% (52/108) of the foals treated for osteomyelitis raced. Foals less than 30 days of age at the time of diagnosis, critically ill foals and those with multiple bones or joints affected were significantly less likely to be discharged from hospital. Multiple septic joints, but not multiple bone involvement, had an unfavourable prognosis for racing. CONCLUSIONS: The prognosis for survival of foals with septic osteomyelitis or osteitis is favourable. Multiple bone or joint involvement is an important short-term prognostic indicator; however, the involvement of multiple joints, but not multiple infected bones, is associated with an unfavourable prognosis for racing.

Blood glucose concentrations in critically ill neonatal foals.

REASONS FOR PERFORMING STUDY: Critical illness is associated with hyperglycemia in humans, and a greater degree and duration of hyperglycemia is associated with nonsurvival. Hypoglycemia is also seen in critically ill humans, and is associated with nonsurvival. This might also be true in the critically ill foal. OBJECTIVES: To investigate the association of blood glucose concentrations with survival, sepsis, and the systemic inflammatory response syndrome (SIRS). METHODS: Blood glucose concentrations at admission (515 foals) and 24 hours (159 foals), 36 hours (95), 48 hours (82), and 60 hours (45) after admission were analyzed. Logistic regression analyses were performed to investigate the association of glucose concentrations with survival, sepsis, a positive blood culture, or SIRS. RESULTS: 29.1% of foals had blood glucose concentrations within the reference range (76-131 mg/dL) at admission, 36.5% were hyperglycemic, and 34.4% were hypoglycaemic. Foals that did not survive to hospital discharge had lower mean blood glucose concentrations at admission, as well as higher maximum and lower minimum blood glucose concentrations in the 1st 24 hours of hospitalization, and higher blood glucose at 24 and 36 hours. Foals with blood glucose concentrations <2.8 mmol/L (50 mg/dL) or >10 mmol/L (180 mg/dL) at admission were less likely to survive. Hypoglycemia at admission was associated with sepsis, a positive blood culture, and SIRS. CONCLUSIONS AND POTENTIAL RELEVANCE: Derangements of blood glucose concentration are common in critically ill foals. Controlling blood glucose concentrations may therefore be beneficial in the critically ill neonatal foal, and this warrants further investigation.

Erythrocytosis and pleural effusion associated with a hepatoblastoma in a Thoroughbred yearling.

A 10-month-old Thoroughbred filly was presented with a 2-month history of recurrent fever and pleural effusion. Major clinical findings were pyrexia and congested mucous membranes. Clinical pathology tests revealed an erythrocytosis, hyperfibrinogenaemia and hyperglobulinaemia. Pleural fluid was seen on ultrasonographic examination of the thorax and analysis of a thoracocentesis sample indicated a lymphocytic, modified transudate. A transtracheal aspirate was normal. The erythrocytosis persisted despite IV fluid therapy. Arterial blood gas analysis and bone marrow aspirate were normal. These findings were indicative of secondary inappropriate erythrocytosis. Ultrasonographic examination of the abdomen showed a large encapsulated heterogeneous mass in the left lobe of the liver. Histopathological evaluation of a biopsy of the mass was indicative of a hepatic carcinoma. The filly was euthanased and necropsy confirmed the presence of a hepatic tumour with no evidence of systemic metastasis. Further histopathological evaluation confirmed the tumour to be an embryonal macrotrabecular epithelial-type hepatoblastoma, a type of hepatoblastoma that has not previously been reported in a horse.

Blood culture isolates and antimicrobial sensitivities from 427 critically ill neonatal foals.

OBJECTIVE: To assist correct decision-making about antimicrobial treatment of equine neonates with septicaemia. DESIGN: Retrospective study of microbial blood culture results obtained from foals less than 7 days of age. METHODS: Microbial blood culture results from foals less than 7 days of age admitted to an intensive care unit between July 1999 and December 2004 were reviewed. Antimicrobial sensitivity was assessed by the Kirby Bauer disc diffusion method. Antimicrobials were defined as an effective first-line choice antimicrobial if greater than 70% of isolates were susceptible. Multiple drug resistance (MDR) was defined as resistance to at least three antimicrobials in different chemical classes or with different mechanisms of resistance. RESULTS: Of the 427 Thoroughbred foals included in the study, a positive blood culture was obtained in 110 foals and 124 microorganisms were isolated. Gram-positive isolates, predominantly Streptococcus/Enterococcus spp, were obtained in 41% of foals. Gram-negative isolates were predominantly of the Enterobacteriaceae family, in particular Escherichia coli. The overall antimicrobial sensitivity of the isolates was low. The Gram-positive organisms had unpredictable sensitivity patterns. MDR was recorded in 32% of isolates. In total, 81% of foals were discharged from hospital and 74.5% of foals with a positive blood culture were discharged. CONCLUSION: With the increasing prevalence of Gram-positive microorganisms and their unpredictable sensitivity patterns, blood cultures remain important in the diagnosis and treatment of equine neonatal septicaemia.

The pathology of bronchointerstitial pneumonia in young foals associated with the first outbreak of equine influenza in Australia.

REASONS FOR PERFORMING STUDY: The first outbreak of equine influenza virus (EIV) infection was confirmed in Australia in 2007. Some EIV-positive young foals died with bronchointerstitial pneumonia, an rare disease process in this age group that is often postulated to be caused by viral infection. OBJECTIVES: The aim of this study was to describe post mortem lesions in EIV-infected foals. METHODS: Post mortem examinations were conducted on 11 young foals (age 2-12 days) submitted to the Scone Veterinary Hospital, NSW over a 2-month period in 2007. The foals had presented with or developed fatal pneumonia, and were known or suspected to be EIV-positive. Equine influenza virus nucleic acid was detected in tissue specimens using an Influenza A group reactive real-time reverse transcriptase PCR assay. RESULTS: Grossly there was diffuse or extensive pulmonary consolidation. Histological changes included: bronchiolar and alveolar necrosis; neutrophilic infiltration; hyaline membrane formation; and hyperplasia and squamous metaplasia of airway epithelium. Tissues for 10 foals were EIV-positive, with a positive nasal swab from the remaining animal. CONCLUSIONS: This is the first detailed pathological description of bronchointerstitial pneumonia associated with EIV infection in young foals. It is also the first series of such cases in which a causative agent has consistently been detected. POTENTIAL RELEVANCE: Given the findings in this outbreak, and a previous outbreak in the UK in 1965 involving a similarly naive population, veterinary clinicians and pathologists should be aware that EIV can cause fatal bronchointerstitial pneumonia in young foals that do not have maternal immunity. The lesions did not differ from those previously reported in foals of various ages with bronchointerstitial pneumonia of other or undefined causes, indicating that this is most likely a stereotypical response to a variety of insults. Therefore, tissue specimens should be obtained from cases of pneumonia in young foals for virological and bacteriological testing.

Generalised granulomatous disease in a horse.

A 6-year-old gelding was referred with a 3-month history of recurrent fever, inappetance, lethargy and weight loss. On clinical examination major findings were depression, thin condition, thrombophlebitis, nodules on the scrotal skin, leukocytosis, hyperfibrinogenaemia and hyperglobulinaemia. Pleural fluid and areas of lung consolidation were seen on ultrasonographic examination of the thorax. A diagnosis of chronic respiratory disease was made. Initially there was a response to antibiotic therapy but the horse was presented 3 months later with continued weight loss, recurrent fever and multifocal skin lesions, characterised by scales, crusts and nodules, affecting the nasal bridge, jugular grooves, ventral neck, withers, scrotum, prepuce, and medial gaskins. Histological evaluation of skin biopsies indicated a granulomatous reaction. On ultrasonographic examination of the thorax multiple hypoechoic lesions consistent with granulomas were seen in both lungs. A diagnosis of generalised granulomatous disease was made. The horse was euthanased at the owner's request. On necropsy examination the main findings were multiple nodules of fibrotic granulomatous inflammation in the lung, heart, liver, gastrointestinal tract and mesenteric lymph nodes, supporting the diagnosis of generalised granulomatous disease.

Synthesis of N-hydroxy peptides: chemical ligation of O-acyl hydroxamic acids.

[process--see text] A novel chemical ligation process is described that results in the construction of N-hydroxy peptides.

Synovectomy of the elbow and radial head excision in rheumatoid arthritis. Predictive factors and long-term outcome.

We carried out a survival analysis of elbow synovectomy (ES) and excision of the radial head (RHE) performed on 171 rheumatoid elbows. The failure criteria were revision surgery (performed or desired) and/or the presence of significant or severe pain. The cumulative survival was 81% at one year which thereafter decreased by an average of 2.6% per year. The strongest predictor for success was a low preoperative range of supination-pronation when corresponding survival curves were compared. A low range of flexion-extension also predicted failure. Combining both factors gave better prediction (failure: 6.3% v 67%), but a long duration of elbow symptoms before surgery predicted failure (72%, p = 0.04). At review, there was a mean gain of 50 degrees in supination-pronation and 11 degrees in flexion-extension; both correlated with success. Failure correlated with recurrence of synovitis, elbow instability, ulnar neuropathy, poor general mobility and poor upper-limb function. The last was independently affected by the severity of RA in the ipsilateral shoulder. Our findings show that although the short-term result of ES and RHE in rheumatoid arthritis is good, the long-term outcome is poor except in a subgroup with more than 50% limitation of forearm rotation.

Rheumatoid synovial cell proliferation, transformation and fibronectin secretion in culture.

OBJECTIVE: There is some experimental evidence that patients with rheumatoid arthritis (RA) have a defect in the control of cellular proliferation. To examine this further, synovial cells from patients with RA and osteoarthritis controls (OA) were studied for phenotypic characteristics of transformation and proliferation. METHODS: Synovial cells grown in vitro were studied to determine the extent of proliferation, anchorage-independent growth, growth under reduced serum conditions, fibronectin secretion, and the presence of cell proliferation antigens. RESULTS: RA synovial cell proliferation was less than that recorded for normal skin fibroblasts and was not increased compared to OA synovial cells. Studies of growth in soft agarose showed no colony formation by RA or OA synovial cells after 28 days, indicating that anchorage-independent growth does not occur. At low serum concentrations RA and OA synovial cells showed similar growth. Fibronectin was constant for each cell line studied, irrespective of the cell number or diagnosis. RA cells did not show an increased rate of fibronectin secretion. RA cells did not show an increased expression of proliferating cell antigens. CONCLUSION: These studies do not support the concept that defective proliferation of synovial cells is a major factor in the pathogenesis of RA.