Publications by authors named "Riitta-Mari Tulamo"

21 Publications

  • Page 1 of 1

Evaluation of the effect of experimentally induced cartilage defect and intra-articular hyaluronan on synovial fluid biomarkers in intercarpal joints of horses.

Acta Vet Scand 2019 May 30;61(1):24. Epub 2019 May 30.

Grupo de Investigación Terapia Regenerativa, Departamento de Salud Animal, Universidad de Caldas, Calle 65 No26-10, Manizales, Caldas, Colombia.

Background: Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-β and TNF-α concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL).

Results: Operation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-β and TNF-α concentrations but compared with baseline, synovial fluid IL-1ra and TNF-α concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen.

Conclusions: Creation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-α concentrations but changes in concentrations of anabolic growth factors TGF-β and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.
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http://dx.doi.org/10.1186/s13028-019-0460-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543688PMC
May 2019

Changes in biomarkers in equine synovial fluid two weeks after intra-articular hyaluronan treatment: a randomised double-blind clinical trial.

BMC Vet Res 2018 Jun 15;14(1):186. Epub 2018 Jun 15.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.

Background: Inflammatory and degenerative activity inside the joint can be studied in vivo via analysis of synovial fluid (SF) biomarkers, which are molecular markers of inflammatory processes and tissue turnover. The aim of this study was to investigate the response of selected biomarkers in the SF after an intra-articular (IA) high-molecular-weight non-animal stabilized hyaluronic acid (NASHA) treatment. Our hypothesis was that prostaglandin E (PGE), substance P, aggrecan chondroitin sulfate 846 epitope (CS846), and carboxypeptide of type II collagen (CPII) concentrations in SF would decrease more in the NASHA than in the placebo group. Twenty-eight clinically lame horses with positive responses to diagnostic IA anaesthesia of the metacarpophalangeal or metatarsophalangeal joints were randomized into treatment (n = 15) and control (n = 13) groups. After collection of baseline SF samples followed by IA diagnostic anaesthesia, horses in the treatment group received 3 ml of a NASHA product IA. Those in the placebo group received an equivalent volume of sterile 0.9% saline solution. The horses were re-evaluated and a second SF sample was obtained after a 2-week period.

Results: CS846 concentration decreased in the NASHA group only (P = 0.010). Both PGE and CPII concentrations decreased within the groups (PGE, P = 0.010 for the NASHA group; P = 0.027 for the placebo group; CPII, P < 0.001 for NASHA group; P = 0.009 for placebo group). No significant treatment effect for any biomarker was found between groups. NASHA induced an increase in white blood cell count; this was significant compared with baseline (P = 0.021) and the placebo group (P = 0.045).

Conclusions: Although the SF concentration of the cartilage-derived biomarker CS846 decreased in the NASHA group, no statistically significant treatment effect of any of the biomarkers were observed between treatment groups. The significant increase in SF white blood cell count after IA NASHA may indicate a mild inflammatory response. However, as no clinical adverse effects were observed, we conclude that IA NASHA was well tolerated.
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http://dx.doi.org/10.1186/s12917-018-1512-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003042PMC
June 2018

Diagnostic accuracy of blood sucrose as a screening test for equine gastric ulcer syndrome (EGUS) in weanling foals.

Acta Vet Scand 2018 Apr 13;60(1):24. Epub 2018 Apr 13.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Background: Equine gastric ulcer syndrome is an important cause of morbidity in weanling foals. Many foals are asymptomatic, and the development of an inexpensive screening test to ensure an early diagnosis is desirable. The objective of this study was to determine the diagnostic accuracy of blood sucrose for diagnosis of EGUS in weanling foals.

Results: 45 foals were studied 7 days before and 14 days after weaning. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL); glandular lesions (GDL); squamous lesions (SQL) and clinically significant gastric lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using ROC curves and calculating the AUC. For each lesion type, sucrose concentration in blood was compared to gastroscopy; and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Cut-off values were selected manually to optimize Se. Because of concerns over the validity of the gold standard, additional Se, Sp, and lesion prevalence data were subsequently estimated and compared using Bayesian latent class analysis. Using the frequentist approach, the prevalence of GL; GDL; SQL and CSL before weaning was 21; 9; 7 and 8% respectively; and increased to 98; 59; 97 and 82% respectively after weaning. At the selected cut-off, Se ranged from 84 to 95% and Sp ranged from 47 to 71%, depending upon the lesion type and time of sampling. In comparison, estimates of Se and Sp were consistently higher when using a Bayesian approach, with Se ranging from 81 to 97%; and Sp ranging from 77 to 97%, depending upon the lesion type and time of sampling.

Conclusions: Blood sucrose is a sensitive test for detecting EGUS in weanling foals. Due to its poor specificity, it is not expected that the sucrose blood test will replace gastroscopy, however it may represent a clinically useful screening test to identify foals that may benefit from gastroscopy. Bayesian latent class analysis represents an alternative method to evaluate the diagnostic accuracy of the blood sucrose test in an attempt to avoid bias associated with the assumption that gastroscopy is a perfect test.
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http://dx.doi.org/10.1186/s13028-018-0377-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899374PMC
April 2018

A comparison of unheated loose housing with stables on the respiratory health of weaned-foals in cold winter conditions: an observational field-study.

Acta Vet Scand 2017 Oct 26;59(1):73. Epub 2017 Oct 26.

Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, 00014, Finland.

Background: Newly weaned horses in Finland are often moved to unheated loose housing systems in which the weanlings have free access to a paddock and a shelter. This practice is considered to be good for the development of young horses. The daily temperatures can stay below - 20 °C in Finland for several consecutive weeks during the winter season. However, the effect of unheated housing in a cold climatic environment on the respiratory health of weanlings under field conditions has not been studied before. This investigation was an observational field-study comprising 60 weanlings among 11 different voluntary participant rearing farms in Finland. Weanlings were either kept in unheated loose housing systems (n = 36) or in stables (n = 24) and were clinically examined on two separate occasions 58 days apart in cold winter conditions.

Results: The odds of clinical respiratory disease were lower in the older foals (log days); OR = 0.009, P = 0.044). The plasma fibrinogen concentration was higher when the available space (m/weanling) in the sleeping hall was smaller (P = 0.014) and it was lower when the sleeping hall was not insulated (P = 0.010). The plasma fibrinogen concentrations at the second examination were lower with a body condition score above 3 (P = 0.070). Standardbreds kept in loose housing systems had a lower body condition score than Finnhorses or Standardbreds kept in stables at both examinations (P = 0.026 and P = 0.007, respectively). Haemoglobin level was lower in weanlings in loose housing systems compared to their counterparts at the first examination (P = 0.037). Finnhorses had higher white blood cell count than Standardbreds at first (P = 0.002) and at the second examination (P = 0.001).

Conclusions: Keeping weanling horses in cold loose housing systems does not seem to increase the occurrence of respiratory disease, but special attention should be focused on ventilation, air quality and feeding-practices. Our field study data suggest it might be advantageous to keep Standardbred foals born late in the season in a stable over the Finnish winter.
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http://dx.doi.org/10.1186/s13028-017-0339-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658990PMC
October 2017

Diagnostic accuracy of blood sucrose as a screening test for equine gastric ulcer syndrome (EGUS) in adult horses.

Acta Vet Scand 2017 Mar 11;59(1):15. Epub 2017 Mar 11.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Background: Equine gastric ulcer syndrome (EGUS) is common in adult horses, particularly those involved in performance disciplines. Currently, detection of EGUS by gastroscopy is the only reliable ante mortem method for definitive diagnosis; however it is unsuitable as a screening test because it is expensive, time consuming, and is not readily available to most veterinarians. Sucrose permeability testing represents a simple, economical alternative to gastroscopy for screening purposes, and the feasibility of this approach in the horse has been previously reported. The aim of this study was to determine the diagnostic accuracy of blood sucrose as a screening test for EGUS in a large group of adult horses with and without naturally occurring gastric disease.

Results: One hundred and one adult horses with or without naturally occurring gastric ulceration were studied. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL), glandular lesions (GDL), squamous lesions (SQL), and clinically significant lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using receiver operator characteristics (ROC) curves and calculating the area under the curve (AUC). For each lesion type, sucrose concentration in blood was compared to gastroscopy, as the gold standard, and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Ulcer grading was performed blindly by one observer; and the results were validated by comparing them with that of two other observers, and calculating the level of agreement. Cut-off values were selected manually to optimize Se. The prevalence of GL, GDL, SQL, and CSL was 83, 70, 53 and 58% respectively. At the selected cut-offs, Se ranged from 51 to 79% and Sp ranged from 43 to 72%, depending upon the lesion type and time of sampling.

Conclusions: Blood sucrose is neither a sensitive or specific test for detecting EGUS in this population of adult horses with naturally occurring gastric ulceration. Further studies aimed at evaluating the performance characteristics of the test in different study populations are warranted. Given the limitations of endoscopy, due consideration should also be given to alternative methods for comparison of blood sucrose with a gold standard.
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http://dx.doi.org/10.1186/s13028-017-0284-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346197PMC
March 2017

Long-term follow-up on recovery, return to use and sporting activity: a retrospective study of 236 operated colic horses in Finland (2006-2012).

Acta Vet Scand 2017 Jan 5;59(1). Epub 2017 Jan 5.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014, Helsinki, Finland.

Background: Surgical treatment of colic is expensive and complications may occur. Information on the prognosis and the use of the horse after surgery for colic is important for surgeons and owners. Current literature on return to athletic function after celiotomy is limited. The present study reviewed surgical cases of the Veterinary Teaching Hospital, Helsinki, Finland for 2006-2012. The aim was to follow the population of horses of different breeds for surgical findings, postsurgical complications, long-term recovery and prognosis. The findings and their influence on survival, return to previous or intended use and performance were assessed.

Results: Most of the operated horses (82.6%; 195/236) recovered from anesthesia and 74.9% (146/195) were discharged. The total follow-up time was 8 years and 10 months and the median survival time 79.2 months. Age of the horse, location of the abdominal lesion (small vs. large intestine), incidence of postoperative colic, surgical site infection, incisional hernia or convalescence time after surgery, did not significantly affect the probability of performing in the previous or intended discipline after the surgery. A majority of the discharged horses (83.7%) was able to perform in the previous or intended discipline and 78.5% regained their former or higher level of performance. Operated horses had 0.18 colic episodes per horse-year during the long-term follow-up. The incidence of colic was 20.0% within the first year after surgery. Horses operated for large intestinal colic were 3.3-fold more prone to suffer postoperative colic than horses operated for small intestinal colic. The majority of the owners (96.3%) were satisfied with the veterinary care and nearly all (98.5%) evaluated the recovery after the colic surgery to be satisfactory or above.

Conclusions: If the horse survives to discharge, prognosis for long-term survival and return to previous level of sporting activity and performance was good after colic surgery in a population of horses of different breeds. None of the factors studied were found to decrease the probability of performing in the same or intended discipline after surgery. The majority of horses were able to return to their previous activity and perform satisfactorily for several years after surgery.
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http://dx.doi.org/10.1186/s13028-016-0273-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216577PMC
January 2017

A randomised, double-blinded, placebo-controlled clinical study on intra-articular hyaluronan treatment in equine lameness originating from the metacarpophalangeal joint.

BMC Vet Res 2016 Mar 23;12:60. Epub 2016 Mar 23.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki,, P.O. Box 57, 00014, Helsinki, Finland.

Background: Intra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) and placebo (saline). Twenty-seven clinically lame horses with a positive response to diagnostic intra-articular anaesthesia of the metacarpophalangeal joint and with no, or at most mild, radiographic changes in this joint were included in the study. Horses in the treatment group (n = 14) received 3 mL of a NASHA product intra-articularly, and those in the placebo group (n = 13) received an equivalent volume of sterile 0.9% saline solution.

Results: The change in the lameness score did not significantly differ between NASHA and placebo groups (P = 0.94). Scores in the flexion test improved more in the NASHA group compared with placebo (P = 0.01). The changes in effusion and pain in flexion were similar (P = 0.94 and P = 0.27, respectively) when NASHA and placebo groups were compared. A telephone interview follow-up of the owners three months post-treatment revealed that 14 of the 21 horses (67%) were able to perform at their previous level of exercise.

Conclusions: In the present study, a single IA NASHA injection was not better than a single saline injection for reducing lameness in horses with synovitis or mild osteoarthritis. However, the results of this study indicate that IA NASHA may have some beneficial effects in modifying mild clinical signs but more research is needed to evaluate whether the positive effect documented ie. reduced response in the flexion test is a true treatment effect.
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http://dx.doi.org/10.1186/s12917-016-0687-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804525PMC
March 2016

Determination of the unsaturated disaccharides of hyaluronic acid in equine synovial fluid by high-performance liquid chromatography and fluorescence detection.

Acta Vet Scand 2015 Mar 4;57:12. Epub 2015 Mar 4.

Department of Equine and Small Animal Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.

Background: The purpose of this study was to develop and validate an analytical method to determine the presence of hyaluronic acid derived disaccharides in equine synovial fluid.

Findings: A high-performance liquid chromatography method for the determination of hyaluronic acid derived unsaturated disaccharides in equine synovial fluid was developed and validated. The method is based on the measurement of unsaturated disaccharides released by digestion of linear hyaluronic acid molecules. The method showed linearity (r(2) = 0.996) over the full working concentration range 0.89-30 mg/l. Relative standard deviation of intra- and inter-day precision ranged from of 4.3-6.7% and 7.1-7.8% respectively. The detection limit was 0.3 mg/l corresponding to 20 mg/l in synovial fluid. Accuracy of the assay was 97-103%. This method was evaluated by determining the concentration of unsaturated disaccharides from hyaluronic acid in synovial fluid of horses with lameness in the metacarpo-/metatarsophalangeal joint localized with positive response to intra-articular anesthesia.

Conclusions: The described method is valid for determination of hyaluronic acid derived disaccharides in equine synovial fluid. This method was applied to a larger research project dealing with a new form of intra-articular therapy in horses with arthritic diseases.
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http://dx.doi.org/10.1186/s13028-015-0098-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350955PMC
March 2015

Development and validation of a gas chromatography-flame ionization detection method for quantifying sucrose in equine serum.

J Vet Diagn Invest 2014 Mar 11;26(2):232-9. Epub 2014 Feb 11.

1Michael Hewetson, Faculty of Veterinary Medicine, PO Box 57, 00014, University of Helsinki, Finland.

A simple and accurate method for quantifying sucrose in equine serum that can be applied to sucrose permeability testing in the horse was developed and validated using gas chromatography with flame ionization detection. The assay provided an acceptable degree of linearity, accuracy, and precision at concentrations of sucrose as low as 2.34 μmol/l and as high as 20.45 μmol/l. Percentage recovery of sucrose from serum ranged from 89% to 102%; repeatability and intermediate precision (relative standard deviation) ranged from 3.6% to 6.7% and 4.1% to 9.3%, respectively. The limit of detection was 0.73 μmol/l. No interfering peaks were observed except lactose, which gave 2 peaks, one of which overlapped partially with sucrose. To evaluate the suitability of the method for quantifying sucrose in serum samples from horses with naturally occurring gastric ulceration, 10 horses with and without naturally occurring gastric ulceration were subjected to sucrose permeability testing. All horses demonstrated an increase in serum sucrose concentration over time following oral administration of sucrose; however, the increase from baseline was significant for horses with gastric ulceration at 45 min (P = 0.0082) and 90 min (P = 0.0082) when compared with healthy horses. It was concluded that gas chromatography with flame ionization detection is a valid method for quantifying sucrose in equine serum and can be applied directly to the analysis of sucrose in equine serum as part of a larger validation study aimed at developing a blood test for the diagnosis of gastric ulcers in horses.
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http://dx.doi.org/10.1177/1040638713519640DOI Listing
March 2014

Application of optical coherence tomography enhances reproducibility of arthroscopic evaluation of equine joints.

Acta Vet Scand 2014 Jan 10;56. Epub 2014 Jan 10.

Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.

Background: Arthroscopy is widely used in various equine joints for diagnostic and surgical purposes. However, accuracy of defining the extent of cartilage lesions and reproducibility in grading of lesions are not optimal. Therefore, there is a need for new, more quantitative arthroscopic methods. Arthroscopic optical coherence tomography (OCT) imaging is a promising tool introduced for quantitative detection of cartilage degeneration and scoring of the severity of chondral lesions. The aim of this study was to evaluate the inter-investigator agreement and inter-method agreement in grading cartilage lesions by means of conventional arthroscopy and with OCT technique. For this aim, 41 cartilage lesions based on findings in conventional and OCT arthroscopy in 14 equine joints were imaged, blind coded and independently ICRS (International Cartilage Repair Society) scored by three surgeons and one PhD-student.

Results: The intra- and inter-investigator percentages of agreement by means of OCT (68.9% and 43.9%, respectively) were higher than those based on conventional arthroscopic imaging (56.7% and 31.7%, respectively). The intra-investigator Kappa coefficients were 0.709 and 0.565 for OCT and arthroscopy, respectively. Inter-investigator Kappa coefficients were 0.538 and 0.408 for OCT and arthroscopy, respectively.

Conclusions: OCT can enhance reproducibility of arthroscopic evaluation of equine joints.
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http://dx.doi.org/10.1186/1751-0147-56-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901375PMC
January 2014

Psychometric testing of the Helsinki chronic pain index by completion of a questionnaire in Finnish by owners of dogs with chronic signs of pain caused by osteoarthritis.

Am J Vet Res 2009 Jun;70(6):727-34

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Fin-00014, Finland.

Objective: To determine the validity, reliability, and sensitivity of a published chronic pain index by completion of a questionnaire in Finnish by owners of dogs with chronic signs of pain caused by osteoarthritis.

Animals: 61 client-owned dogs with osteoarthritis.

Procedures: Validity, internal consistency, and repeatability testing of the questionnaire were evaluated by completion of questions in Finnish by owners of 61 dogs; the questionnaire was named the Helsinki chronic pain index (HCPI). Sensitivity testing of the questionnaire was determined from data of 2 smaller groups of dogs treated with carprofen (n = 17) or placebo (17). Owners completed the questionnaire 5 times during a 16-week period. Psychometric properties of the HCPI were evaluated.

Results: Principal component analysis yielded only a single stable component, indicating that the HCPI was best explained as an 11-item single construct index of chronic pain. Changes in the HCPI correlated well with change in quality of life and with change in the mobility visual analogue scale (r = 0.72 and r = 0.67, respectively), indicating a high predictive validity. Internal consistency (Cronbach A value = 0.82) and test-retest reliability (intraclass correlation coefficient = 0.84 for items and 0.92 for the HCPI) were high. Changes in scores (from baseline to treatment and back to no treatment) between the carprofen treatment group and placebo control group were significant, indicating high sensitivity.

Conclusions And Clinical Relevance: The Finnish version of the HCPI provided a valid, reliable, and responsive tool for assessment of response to treatment in dogs with osteoarthritis.
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http://dx.doi.org/10.2460/ajvr.70.6.727DOI Listing
June 2009

Evaluating Complementary Therapies for Canine Osteoarthritis Part I: Green-lipped Mussel (Perna canaliculus).

Evid Based Complement Alternat Med 2009 Sep 29;6(3):365-73. Epub 2007 Oct 29.

Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, PO Box 57, FI-00014, Finland.

A green-lipped mussel (GLM) preparation was evaluated in a randomized, double-controlled and double-blinded clinical trial. It was hypothesized that the treatment effect would be less than that of the positive control (carprofen) but more than that of the negative control (placebo). Forty-five dogs with chronic pain and a radiographic diagnosis of osteoarthritis that were randomly allocated into one of three groups completed the study. All dogs were fed the test products or placebo for 8 weeks. The dogs were evaluated four times, at 4-week intervals. Six different variables were assessed: veterinary-assessed mobility index, two force plate variables, owner-evaluated chronic pain index and pain as well as locomotion visual analogue scales (VASs). Intake of extra carprofen was also evaluated. A chi-squared and a Mann-Whitney test were used to determine significance between groups. When changed to dichotomous variables, there were more dogs in the GLM than in the placebo group that improved, according to veterinary-assessed mobility, owner-evaluated chronic pain index and pain VAS (P = 0.031, P = 0.025, P = 0.011, respectively). For the same three, the odds ratio and their confidence interval were over one. The extent of improvement was significantly different between the GLM and the control in veterinary-assessed mobility (P = 0.012) and pain VAS (P = 0.004). In conclusion, GLM alleviated chronic orthopedic pain in dogs although it was not as effective as carprofen. As no side-effects were detected, GLM may be beneficial in dogs e.g. when non-steroidal anti-inflammatory drugs cannot be used.
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http://dx.doi.org/10.1093/ecam/nem136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722199PMC
September 2009

Evaluating complementary therapies for canine osteoarthritis--Part II: a homeopathic combination preparation (Zeel).

Evid Based Complement Alternat Med 2009 Dec 25;6(4):465-71. Epub 2007 Oct 25.

Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Finland.

A homeopathic combination preparation (HCP) for canine osteoarthritic pain was evaluated in a randomized, double-controlled and double-blinded clinical trial. Forty-four dogs with osteoarthritis (OA) that were randomly allocated into one of three groups completed the study. All dogs were fed test products or placebo for 8 weeks. The dogs were evaluated at the clinic four times, with 4-week intervals. Six different variables were assessed: veterinary-assessed mobility, two force plate variables, an owner-evaluated chronic pain index and pain and locomotion visual analogue scales (VASs). Intake of extra non-steroidal anti-inflammatory drugs was also evaluated. A Chi-squared test and a Mann-Whitney test were used to determine significant improvement between groups. When changed into dichotomous responses of 'improved' or 'not improved' three out of the six variables showed a significant difference (P = 0.016, P = 0.008, P = 0.039) in improved dogs per group, between the HCP group and the placebo group. The odds ratios were over one for the same variables. As extent of improvement in the variables from start to end of treatment, the HCP product was significantly more improved in four (P = 0.015, P = 0.028, P = 0.049, P = 0.020) of the six variables, compared with the placebo. Our results indicated that the HCP Zeel(R) was beneficial in alleviating chronic orthopedic pain in dogs although it was not as effective as carprofen.
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http://dx.doi.org/10.1093/ecam/nem143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781775PMC
December 2009

Long-term bone tissue reaction to polyethylene oxide/polybutylene terephthalate copolymer (Polyactive) in metacarpophalangeal joint reconstruction.

Biomaterials 2008 Jun 11;29(16):2509-15. Epub 2008 Mar 11.

Department of Hand Surgery, Helsinki University Central Hospital, FIN-00029 HUS, Helsinki, Finland.

The poly-L/D-lactide 96/4 joint scaffolds are used to engineer fibrous tissue joints in situ for the reconstruction of metacarpophalangeal joints. In this experimental study, a supplementary elastomeric stem made of Polyactive 1000PEO70PBT30 (a segmented block copolymer of polyethylene oxide and polybutylene terephtalate with 70/30 PEO/PBT ratio) was used to anchor the joint scaffold in the arthroplasty space. Eleven resected fifth metacarpophalangeal joints of minipig were reconstructed and evaluated radiologically and histologically for 3 years. Plain joint scaffold and Swanson silicone implant arthroplasties (11 of each) in metacarpophalangeal joints of minipig served as controls. Altogether fore limbs of eighteen minipigs were operated for the study. Deleterious tissue reaction with dramatic signs of osteolysis and inflammatory foreign-body reaction was observed around the Polyactive stems. The mean maximum diameter of the osteolytic stem cavity was statistically wider when compared to the mean maximum diameter of Swanson implant group during the first postoperative year. Numerous osteoclasts were found at the margins of the osteolytic areas. No direct bone contact could be seen. At 1 year osteoblastic regeneration and formation of new trabecular bone followed. Finally the foreign-body reaction settled, but the adjoining bones were at this stage highly sclerotic and composed of coarse trabeculae. In contrary to previous in vivo studies suggesting biocompatibility, osteoconductivity and capability to bond to bone, Polyactive 1000PEO70PBT30 stem in this setting caused massive osteolytic lesions and foreign-body reactions.
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http://dx.doi.org/10.1016/j.biomaterials.2008.02.013DOI Listing
June 2008

The use of biodegradable scaffold as an alternative to silicone implant arthroplasty for small joint reconstruction: an experimental study in minipigs.

Biomaterials 2008 Feb 14;29(6):683-91. Epub 2007 Nov 14.

Department of Hand Surgery, Helsinki University Central Hospital, P.O. Box 266, FIN-00029 HUS, Helsinki, Finland.

Biodegradable poly-L/D-lactide (P(L/D)LA) 96/4 joint scaffold arthroplasty is a recently clinically introduced concept in the reconstruction of small joints, however its histology and function in vivo is unknown. In this experimental study on 11 minipigs the fifth metacarpophalangeal joints were reconstructed using a P(L/D)LA 96/4 joint scaffold or Swanson silicone implant. They were evaluated until 3 years. The P(L/D)LA 96/4 joint scaffold formed a porous interposition spacer, which maintained the arthroplasty space and induced fibrous tissue in-growth in situ. No differences were found in the range of motion or arthroplasty space width between the study groups. The P(L/D)LA 96/4 joint scaffold was initially filled with vascular, loose connective tissue. Along with degradation of the scaffold, the in-grown connective tissue matured and condensed turning into dense fibrous connective tissue. After 3 years, the P(L/D)LA 96/4 joint scaffold had almost completely degraded and been replaced by dense fibrous connective tissue. These findings indicate that P(L/D)LA 96/4 joint scaffold arthroplasty leads to the formation of a functional fibrous joint. The avoidance of permanent foreign material makes the biodegradable joint scaffold an attractive alternative for small joint arthroplasty.
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http://dx.doi.org/10.1016/j.biomaterials.2007.10.037DOI Listing
February 2008

Repair of radial fractures in toy breed dogs with self-reinforced biodegradable bone plates, metal screws, and light-weight external coaptation.

Vet Surg 2005 Jan-Feb;34(1):11-7

Espoo Animal Hospital, Espoo, Finland.

Objective: To describe a surgical technique for, and outcome after, treatment of radial fractures with biodegradable self-reinforced polylactide plates and metal screws, and external coaptation.

Study Design: Prospective clinical study.

Sample Population: Eleven Toy breed dogs.

Methods: Radial fractures were repaired by application of a single or 2 stacked biodegradable self-reinforced polylactide plates (poly-L/D, L-lactide, stereocopolymer [LL-and DL-lactide ratio 70/30]; SR-PLA (70/30) implants) secured with metal screws, and light-weight external coaptation. Healing was evaluated clinically and by radiography at 2, 4, 6, 8, 9, 12, 24-26 weeks, and at 1 and 2 years. Owners were interviewed 3 years after surgery.

Results: Radial fracture lines disappeared within 4-14 weeks in 10 dogs; an implant failed in 1 dog. Ambulation was excellent for healed fractures. Excessive skin tension led to removal of implants in 1 dog and suture repair in another dog. No foreign body reaction from implant degradation was observed and the plate was usually no longer palpable at 2 years. One dog had a fracture through a screw hole at 1 year.

Conclusion: Healing and complication rates after repair of radial fractures with SR-PLA (70/30) plates were considered similar or better than reported after repair with metallic plates or external fixation in Toy breed dogs. No radiographic signs of osteopenia were identified under the plate during follow-up.

Clinical Relevance: Biodegradable polylactide plates could be considered as an alternative to metal plates for radial fracture repair in Toy breed dogs, however available plates are likely not strong enough when used as a single plate. Implant removal is usually not needed.
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http://dx.doi.org/10.1111/j.1532-950X.2005.00003.xDOI Listing
August 2005

Tissue reactions of subcutaneously implanted mixture of epsilon-caprolactone-lactide copolymer and tricalcium phosphate. An electron microscopic evaluation in sheep.

J Mater Sci Mater Med 2003 Oct;14(10):913-8

Department of Oral and Maxillofacial Surgery, Helsinki University Central Hospital, Finland.

Biodegradable polymers, mainly derivates of alpha-hydroxy acids, are widely used today in oral- and maxillofacial surgery, orthopedics, and other fields of surgery. These biomaterials are well tolerated by living tissue and fracture fixation devices made of polylactic or polyglycolic acid are clinically widely used today. Still, there are some problems in application of biodegradable polymers. Abacterial inflammatory reactions have been noticed after the clinical introduction of these devices. Both swelling and pain at the site of implantation have also been reported. The etiology of this inflammatory reaction is still unknown, despite the numerous studies. Therefore, the aim of the present study was to further characterize this inflammatory reaction in detail, by electronmicroscopy. We prepared a mixture of epsilon-caprolactone-lactide copolymer and tricalcium phosphate and placed it in the dermis in 12 sheep. Follow-up times were 9, 14, 24, and 52 weeks. We found that the mixture caused a mild inflammatory reaction. There were no signs of cell damage. Fibroblasts, macrophages, and eosinophils were found adjacent to the copolymer. The mixture is easy to handle and can be moulded into different shapes in room temperature. The results encourage us to continue our studies to develop a filling material for bone defects.
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http://dx.doi.org/10.1023/a:1025642912270DOI Listing
October 2003

Effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate on adult equine cartilage.

J Rheumatol 2004 Feb;31(2):321-8

Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Objective: To analyze the effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate (166Ho-FHMA) on articular cartilage in 6 adult horses.

Methods: Arthritic changes and mechanical properties of articular cartilage were evaluated with arthroscopy and postmortem microscopic analyses. Glycosaminoglycan content was measured by safranin-O staining combined with digital densitometry, uronic acid analyses, and dimethylene blue binding assay. 35S-sulfate labeling and autoradiography were used to localize proteoglycan synthesis and to characterize proteoglycan structures using SDS-agarose gel electrophoresis. Northern hybridizations were performed to measure the mRNA levels for aggrecan and pro-a1(II) collagen in cartilage samples.

Results: Histological signs of degeneration were present in the articular cartilage of both control and radiosynovectomized equine joints. Radiosynovectomy did not aggravate degenerative changes or significantly alter the matrix glycosaminoglycan content. A slightly decreased size of proteoglycan monomers was observed 2 months after 166Ho-FHMA radiosynovectomy. Tissue analysis of extracted proteoglycans revealed lower 35S incorporation after radiosynovectomy, but corresponding changes could not be observed in aggrecan mRNA levels. Transient downregulation of pro-a1(II) collagen mRNA transcription was observed 5 days after 166Ho-FHMA radiosynovectomy.

Conclusion: 166Ho-FHMA treatment did not markedly affect the composition or morphology of adult articular cartilage showing mild degeneration. However, minor degradation of proteoglycan monomers and transient downregulation of pro-a1(II) collagen mRNA were observed.
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February 2004

Radiation synovectomy with holmium-166 ferric hydroxide macroaggregate in equine metacarpophalangeal and metatarsophalangeal joints.

Vet Surg 2003 Jul-Aug;32(4):402-9

Faculty of Veterinary Medicine, Department of Clinical Veterinary Sciences, University of Helsinki, Finland.

Objectives: To evaluate the effects of radiation synovectomy (RSYN) with holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) on synovium and synovial fluid in normal metacarpo- and metatarsophalangeal joints of horses and to determine intraarticular distribution of radioactivity after Ho-166 FHMA treatment.

Study Design: Either Ho-166 FHMA or nonradioactive Ho-165 FHMA was injected into metacarpo- or metatarsophalangeal joints.

Animals: Six adult mixed-breed horses without any clinical evidence of metacarpo- or metatarsophalangeal joint disease.

Methods: Joints were injected with a single high dose of Ho-166 FHMA (mean, 1,000 MBq/joint) or a nonradioactive Ho-165 FHMA preparation (controls). Clinical examination, arthroscopy, synovial fluid analyses, and histologic studies were performed to detect effects of RSYN. Scintigraphy was used to localize intraarticular distribution of Ho-166 FHMA.

Results: Ho-166 FHMA treatment induced joint inflammation leading to regional edema, effusion, and scar tissue formation. Scintigraphy revealed the highest intensity of radioactivity in the proximal plantar joint pouch, at which the Ho-166 FHMA treatment caused multifocal necrosis. In the dorsal joint pouch, however, arthroscopic study and histologic analysis showed very little effect of RSYN. There was no regeneration of synovium evident within 2 months. Synovial fluid protein concentration was significantly (P <.01) elevated, and some residual radioactivity remained for 5 days after Ho-166 FHMA injection.

Conclusions: Injection of a single high dose of Ho-166 FHMA caused multifocal necrosis of synovium and deep, soft-tissue injury in equine fetlock joints.

Clinical Relevance: Inflamed equine joints with synovial lining hyperplasia could benefit from Ho-166 FHMA-induced radiation synovectomy if excessive scar tissue formation can be avoided.
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http://dx.doi.org/10.1053/jvet.2003.50039DOI Listing
September 2003

Evaluation of methods for assessment of pain associated with chronic osteoarthritis in dogs.

J Am Vet Med Assoc 2003 Jun;222(11):1552-8

Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland Fin-00014.

Objective: To identify variables and evaluate methods for assessing chronic pain in dogs.

Design: Prospective study.

Animals: 41 dogs with canine hip dysplasia (CHD), and 24 apparently healthy dogs with no history of pain.

Procedure: 2 veterinarians evaluated the dogs' locomotion and signs of pain. Owners of dogs with CHD and control dogs answered a questionnaire regarding their dogs' demeanor, behavior, and locomotion (descriptive scales) and assessed pain and locomotion (visual analog scales). Plasma concentrations of several stress-related hormones were determined, and 13 radiologic variables were assessed in affected hip joints.

Results: For many of the questions, answers provided by owners of dogs with CHD differed significantly from those of owners of control dogs. Stress hormone concentrations differed significantly between dogs with CHD and controls, but individual variation was too great for them to be of value in pain assessment. None of the radiologic variables examined correlated well with owner or veterinarian pain scores.

Conclusions And Clinical Relevance: Chronic pain could be assessed in dogs with CHD through completion of the study questionnaire by a person familiar with the pet (eg, owner) after receiving appropriate education in its use. Eleven variables were identified as being potentially useful in assessment of chronic pain in dogs.
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http://dx.doi.org/10.2460/javma.2003.222.1552DOI Listing
June 2003

Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate.

Nucl Med Biol 2002 Jul;29(5):593-8

Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FIN-00014 University of Helsinki, Helsinki, Finland.

Holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) particles possess two important properties for radiosynovectomy; relatively short half-life of the radioisotope and appropriate carrier size. Both these minimize radioactive leakage from the treated joint. This study was conducted to assess the effects of Ho-166 FHMA on synovium and synovial fluid in rabbit knee joints. Whole-knee autoradiography was utilized to determine distribution of radioactivity after intra-articular Ho-166 FHMA injection. Intra-articular injection of Ho-166 FHMA resulted in focal acute radiation necrosis in synovial lining but no hyperplasia of synoviocytes. Later, subsynovial fibrosis became evident. White blood cell and total protein levels in the joint fluid were elevated because of intra-articular inflammation due to the acute effects of radiation. Whole knee autoradiograms showed uneven distribution of the radionuclide along the synovium and extraarticular leakage on the third day after treatment.
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http://dx.doi.org/10.1016/s0969-8051(02)00317-7DOI Listing
July 2002
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