The Effect of Local Heat and Cold Therapy on the Intraarticular and Skin Surface Temperature of the Knee

Objective. To evaluate the effects of local application of ice chips, ligno-paraffin, short-wave diathermy, and nitrogen-cold air on skin and intraarticular temperature. Methods. Forty-two healthy subjects were divided into 4 treatment groups. A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin, and changes in temperature over 3 hours, by treatment group, were recorded. Results. The mean skin surface temperature dropped from 27.9°C to 11.5°C after application of ice chips, and from 28.8°C to 13.8°C after application of cold air. The mean intraarticular temperature decreased from 31.9°C to 22.5°C and from 32.9°C to 28.8°C, respectively, after these 2 treatments. Short-wave diathermy increased skin temperature by 2.4°C; intraarticular temperature was increased only 1.4°C by short-wave diathermy. Treatment with ligno-paraffin increased the skin surface temperature 8.9°C; the temperature in the joint cavity was increased 3.5°C. Conclusion. The use of short-wave diathermy and superficial heat packs in the treatment of patients with arthritis may potentially cause harm by increasing intraarticular temperature. This may have major implications regarding treatment policy for patients with arthritis.     

The effect of local heat and cold packs on the skin temperature at the knee joint

Using the infrared radiometer KT 41, skin temperature of the knee joint was measured in 5 healthy persons on five different points. With the same method skin temperature of knee joints was estimated after hot mud packs of 20 minutes duration and cold packs with frozen bags of 30 minutes duration. The highest temperatures were estimated near the popliteal space, the lowest temperatures on the patella. During 24 hours, a distinct periodical course of skin temperature could be observed. After the hot pack skin temperature of the treated joint significantly rose; after 1 hour the average temperature before heat application was reached again. After cold application with deeply frozen bags, skin temperature dropped drastically and remained colder than pretreatment temperature for almost 5 hours. Heat application did not influence skin temperature of untreated contralateral knee but during cold application also the temperature of untreated knee slightly decreased. Considering the correlation between skin temperature and intraarticular temperature of joints, the effect of local heating and cooling seems to be more intense than supposed and confirms the therapeutic benefit of heat and cold in rheumatology.     

Somatostatin-induced modulation of inflammation in experimental arthritis

Objective. To study the antiinflammatory effect of different doses of intraarticular somatostatin in experimental arthritis in rabbits. Methods. Chronic arthritis was induced by a single injection of fibrin into the knee joint of rabbits previously sensitized to this antigen. The effects of sequential intraarticular injections of somatostatin into the rabbit knee, at doses of 500, 750, and 1,000 μg, were monitored by measuringknee joint circumferences and hematologic parameters. The measurements were compared with those obtained following use of triamcinolone acetonide and placebo. At the end of the experiments, the knee joints were examined histologically. Results. Somatostatin treatment induced a statistically significant and dose-related reduction of knee joint swelling. This effect was shorter than that produced by triamcinolone acetonide; however, the antiinflammatory activity elicited by successive doses of triamcinolone acetonide declined both in extent and duration, while the effects of somatostatin remained unchanged at each successive treatment. Histopatho-logic observations showed that both somatostatin and triamcinolone acetonide reduced the inflammatory signs in the joint structures, although triamcinolone acetonide appeared to be more effective. Conclusion. These findings suggest that somatostatin exerts an antiinflammatory effect in this model of experimental arthritis and may represent a valid and safer alternative to corticosteroids for intraarticular therapy of arthritis.     

Effects of cryotherapy on arthrogenic muscle inhibition using an experimental model of knee swelling

Objective

Arthrogenic muscle inhibition (AMI) contributes to quadriceps weakness and atrophy in knee arthritis and following joint injury. This laboratory‐based study examined the efficacy of cryotherapy in reducing quadriceps AMI caused by intraarticular swelling.

Methods

Sixteen subjects without knee pathology participated, and were randomly assigned to a cryotherapy (n = 8) or control (n = 8) group. Surface electromyography (EMG) from vastus medialis and quadriceps torque measurements were recorded during maximum effort isometric contractions. All subjects then received an experimental joint infusion, whereby dextrose saline was injected into the knee to an intraarticular pressure of 50 mm Hg. EMG and torque measurements were repeated. Thereafter, the cryotherapy group had ice applied to the knee for 20 minutes while the control group did not receive an intervention. EMG and torque measurements were again collected. Quadriceps peak torque, muscle fiber conduction velocity (MFCV), and the root mean square (RMS) of EMG signals from vastus medialis were analyzed.

Results

Quadriceps peak torque, MFCV, and RMS decreased significantly following joint infusion (P ≤ 0.001). Cryotherapy led to a significant increase in quadriceps torque and MFCV compared with controls (P < 0.05). The difference in RMS did not reach statistical significance (P = 0.13).

Conclusion

The study demonstrated that cryotherapy is effective in reducing AMI induced by swelling. Cryotherapy may allow earlier and more effective quadriceps strengthening to occur in patients with knee joint pathology.     

Joint capsular stiffness in knee arthritis. Relationship to intraarticular volume, hydrostatic pressures, and extensor muscle function

Increased intraarticular hydrostatic pressure (Pia) may inhibit juxtaarticular muscle function, obstruct blood supply to joint structures and promote anoxic joint destruction in chronic arthritis. Joint capsular stiffness together with synovial fluid volume determines Pia at rest. Seventeen knee joints with effusive arthritis and different degrees of radiological cartilage involvement in 13 patients with chronic arthritis were examined. Since capsular elastance was difficult to standardize, we introduce a measure of joint capsular stiffness where the intraarticular volume yielding a pressure of 50 mm Hg (V50) is used. After normalization of injected volumes according to the V50, pressure volume curves became similar. Intraarticular hydrostatic pressure and maximal voluntary isometric extensor torque were measured simultaneously, while altering the intraarticular fluid volume in 9 knee joints. In 5 of these, quantified electromyography (EMG) of the vastus medialis and lateralis portion of the quadriceps muscle was also monitored. Progressive inhibition of extensor torque and EMG was found as the intraarticular pressure volume was increased in both intact and destroyed joints. No difference in inhibition was found for the 2 portions of quadriceps muscle tested. Increased intraarticular hydrostatic pressure Pia levels between 200 and 1150 mm Hg were observed during maximal voluntary activation of extensor muscles. The reproducibility was good for all variables studied. In a few instances evidence of intraarticular compartmentalization was found at low volumes. We conclude that the V50 is a convenient expression of capsular stiffness. Furthermore, increasing Pia caused by joint effusion inhibits knee extensor muscle function and impairs synovial blood flow. Awareness of these relations will facilitate more rational therapeutic approaches in chronic arthritis.     

Intraarticular injections of hyaluronan in patients with cartilage abnormalities and knee pain

Objective. To compare the effect of intraarticular injections of hyaluronan and placebo (vehicle, saline) in patients with knee pain on exertion and with joint cartilage abnormalities. Methods. Fifty-two patients with arthroscopically verified deep cartilage fissures and villus-like flakes in the symptomatic knee were randomly assigned to receive intraarticular injections of 2.5 ml of either hyaluronan or vehicle, weekly for 5 weeks. The effect was evaluated by both primary and secondary parameters of efficacy at 2, 4, 13, 26, and 52 weeks. Results. At the followup visits, both groups had improvement from baseline; however, there was no difference between the groups in any of the relevant variables at any time point. Conclusion. The effects of intraarticular hyaluronan do not differ significantly from those of placebo in patients with knee pain and cartilage disease.     

Lower blood return temperature than core temperature as a causal factor of decreased cardiac output assessed by transpulmonary thermodilution during blood purification

We aimed to evaluate whether cardiac output assessed by transpulmonary thermodilution during blood purification is affected by the difference between the blood return temperature and core temperature. We applied different blood return temperatures using a thermostat bath during blood purification in four pigs. After the blood return temperature stabilized and blood purification process stopped, the cardiac output assessed by transpulmonary thermodilution was measured. The thermostat bath was set at 35°C, 40°C, 45°C, and 50°C, with the order changed at random; four measurements were made at each temperature. Cardiac function was evaluated by echocardiography when ice‐cold saline was administered in a pig. A decrease in the blood return temperature resulted in decreased cardiac output assessed by transpulmonary thermodilution, whereas an increase resulted in increased cardiac output assessed by transpulmonary thermodilution. Echocardiography revealed that the change in the blood return temperature did not affect the left ventricular ejection fraction.     

The effect of acute cold and warm ambient temperatures on the thyroid hormone concentration in blood plasma,blood supply,and oxygen consumption in Japanese quail

Blood supply to the thyroid gland, blood plasma T₄ and T₃ concentration, oxygen consumption, and body temperature were measured in Japanese quail in cold (?1 to ?6°) and warm (34 to 35°) ambient temperatures. The most pronounced changes were noted during the first hour of temperature influence. During this time, in cold ambient temperature, the blood supply of the thyroid and T₃ concentration in the plasma increased 2.14- and 3.24-fold, respectively. The T₄ concentration initially decreased significantly then it increased. In a warm ambient temperature constant decreases in blood supply and T₄ concentration were noted. The plasma T₃ concentration was significant greater at 5 and 48 hr after warm exposure. Oxygen consumption was elevated within the first hour of cold diuration, a decline in oxygen consumption was not observed before Hour 12 of heat influence. A statistically significant change in rectal and skin temperatures occurred chiefly during cold exposure.     

Asymmetrical effects of albumin on transsynovial fluid movement.

The effect of intraarticular infusions of albumin solution on transsynovial flow was studied in healthy rabbit knee joints and compared with the effect of albumin solution perfused through the synovial microcirculation. Increasing intravascular albumin levels enhanced fluid absorption from the joint cavity, whereas increasing intraarticular albumin levels reduced the absorption rate. The slope of intraarticular pressure-versus-absorption rate plots was reduced by albumin in proportion to the reduction in fluidity (1/viscosity). When joint pressure was held constant, the transsynovial absorption rate was reduced by albumin in excess of the fluidity reduction and even reversed to filtration into the joint cavity. Thus intraarticular albumin acts by a dual mechanism, namely by increasing synovial interstitial fluid viscosity and by exerting a peri-capillary oncotic pressure. However, the latter effect was much less than that of intravascular albumin. Reasons for this are discussed.     

Assessment of rheumatoid inflammation in the knee joint. A reappraisal.

Subjective pain score, clinical assessment, 99m technetium joint uptake, infrared thermography, and thermistor skin temperature measurements were evaluated and compared in patients with rheumatoid knee treated with intra-articular hydrocortisone. In 11 patients with definite and classical rheumatoid arthritis, 10 of whom had unilateral knee involvement, the affected knee joints were assessed by the above techniques before and at intervals after treatment of up to 14 days. The anti-inflammatory property of the steroid therapy was shown by all the assessment parameters, values having decreased significantly from the pretreatment values. However, the only parameter still showing a statistically significant decrease on the 14th post-treatment day was 99mTc joint uptake. Correlations were obtained between the two clinical measurements assessed by a physician i.e. pain score and index of joint inflammation. Both of these also correlated with the 99mTc joint uptake but not with skin temperature measurements. Using the clinical assessments as a yardstick, 99mTc joint uptake seemed to provide a useful index of changes in disease activity in the group as a whole. However, skin temperature measurements by infrared thermography and by the thermistor were of considerably less value.     

Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer.

Gene therapy offers a radical different approach to the treatment of arthritis. Here we have demonstrated that two marker genes (lacZ and neo) and cDNA coding for a potentially therapeutic protein (human interleukin 1-receptor-antagonist protein; IRAP or IL-1ra) can be delivered, by ex vivo techniques, to the synovial lining of joints; intraarticular expression of IRAP inhibited intraarticular responses to interleukin 1. To achieve this, lapine synoviocytes were first transduced in culture by retroviral infection. The genetically modified synovial cells were then transplanted by intraarticular injection into the knee joints of rabbits, where they efficiently colonized the synovium. Assay of joint lavages confirmed the in vivo expression of biologically active human IRAP. With allografted cells, IRAP expression was lost by 12 days after transfer. In contrast, autografted synoviocytes continued to express IRAP for approximately 5 weeks. Knee joints expressing human IRAP were protected from the leukocytosis that otherwise follows the intraarticular injection of recombinant human interleukin 1 beta. Thus, we report the intraarticular expression and activity of a potentially therapeutic protein by gene-transfer technology; these experiments demonstrate the feasibility of treating arthritis and other joint disorders with gene therapy.     

Elevated substance p and accelerated cartilage degradation in rabbit knees injected with interleukin-1 and tumor necrosis factor

Cytokines, interleukin-1 (IL-1), tumor necrosis factor α, and the neurotransmitter, substance P, have been implicated in the pathogenesis of arthritis because they stimulate synovial cells to secrete prostaglandin E₂ and collagenase in vitro. We investigated in vivo changes in intraarticular substance P and the degradation of cartilage proteoglycan in response to intraarticular cytokine injections in rabbits. Twenty-four hours after a single injection of 10 ng, 30 ng, or 100 ng of recombinant human IL-1α (rHuIL-1α) per joint, the mean ± SEM levels of substance P detected in the cell-free joint lavage fluid were 250 ± 67 fmoles, 480 ± 60 fmoles, and 530 ± 130 fmoles (n = 4–5), respectively. The level of substance P in the contralateral knees injected with diluent was 58 ± 8 fmoles (n = 12). The level of substance P had increased by 2 hours after IL-1 injection and remained elevated in the joint 48 hours after injection. Cytokineinduced proteoglycan depletion was also time- and dose-dependent. Proteoglycan concentrations in articular cartilage dissected from the weight-bearing condyles were calculated as the ratio of sulfated glycosaminoglycan measured using 1,9-dimethylmethylene blue: hydroxyproline. After 48 hours, 10 ng, 30 ng, or 100 ng of rHuIL-la per joint decreased proteoglycan levels by 9 ± 4%, 14 ± 4%, and 21 ± 3% (n = 8), respectively. Likewise, the injection of recombinant human tumor necrosis factor α induced depletion of intraarticular substance P and cartilage proteoglycan.     

Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat

OBJECTIVE: To determine if the new, orally active C5a receptor antagonist, the cyclic peptide AcF-[OPdChaWR], reduces the severity of pathology in a rat model of immune-mediated monarticular arthritis. METHODS: Arthritis was induced in the right knee of previously sensitized rats by the intraarticular injection of methylated bovine serum albumin. Rats were examined for either 14 days or 28 days, or for 49 days following a second antigen challenge at 28 days. The C5a antagonist (1 or 3 mg/kg/day) and/or ibuprofen (30 mg/kg/day) were administered orally on a daily basis either before or after arthritis induction. RESULTS: Rats receiving AcF-[OPdChaWR] had significant reductions in right knee swelling, gait disturbance, lavaged joint cell numbers, and right knee histopathology, as well as in serum levels of tumor necrosis factor alpha (TNFalpha) and intraarticular levels of interleukin-6 and TNFalpha on day 14. In the 14- and 28-day studies, ibuprofen resulted in a similar reduction in gait abnormalities and intraarticular inflammatory cells compared with the C5a antagonist, but was less effective in reducing knee swelling over the course of the study and had no effect on knee histopathology. Combination therapy with AcF-[OPdChaWR] and ibuprofen resulted in no greater efficacy than with the C5a antagonist alone. Rats injected twice with the antigen in the 49-day study displayed the most severe histopathology and this, as well as knee swelling and gait abnormalities, was significantly reduced by repeated treatment with the C5a antagonist. CONCLUSION: An agent that inhibits the action of C5a in this model significantly reduced joint pathology, while ibuprofen was not effective. C5a antagonists could therefore have broader therapeutic benefits than nonsteroidal antiinflammatory drugs as antiarthritic agents for rheumatoid arthritis.     

Antiarthritic activity of an orally active C5a receptor antagonist against antigen‐induced monarticular arthritis in the rat

Objective

To determine if the new, orally active C5a receptor antagonist, the cyclic peptide AcF‐[OPdChaWR], reduces the severity of pathology in a rat model of immune‐mediated monarticular arthritis.

Methods

Arthritis was induced in the right knee of previously sensitized rats by the intraarticular injection of methylated bovine serum albumin. Rats were examined for either 14 days or 28 days, or for 49 days following a second antigen challenge at 28 days. The C5a antagonist (1 or 3 mg/kg/day) and/or ibuprofen (30 mg/kg/day) were administered orally on a daily basis either before or after arthritis induction.

Results

Rats receiving AcF‐[OPdChaWR] had significant reductions in right knee swelling, gait disturbance, lavaged joint cell numbers, and right knee histopathology, as well as in serum levels of tumor necrosis factor α (TNFα) and intraarticular levels of interleukin‐6 and TNFα on day 14. In the 14‐ and 28‐day studies, ibuprofen resulted in a similar reduction in gait abnormalities and intraarticular inflammatory cells compared with the C5a antagonist, but was less effective in reducing knee swelling over the course of the study and had no effect on knee histopathology. Combination therapy with AcF‐[OPdChaWR] and ibuprofen resulted in no greater efficacy than with the C5a antagonist alone. Rats injected twice with the antigen in the 49‐day study displayed the most severe histopathology and this, as well as knee swelling and gait abnormalities, was significantly reduced by repeated treatment with the C5a antagonist.

Conclusion

An agent that inhibits the action of C5a in this model significantly reduced joint pathology, while ibuprofen was not effective. C5a antagonists could therefore have broader therapeutic benefits than nonsteroidal antiinflammatory drugs as antiarthritic agents for rheumatoid arthritis.

     

Heat loss during cold exposure in ADULT and AGED C57BL/6J mice

Metabolic heat production (MHP), colonic temperature (Tco), and nonevaporative (dry) heat loss were measured in ADULT and AGED C57BL/6J male mice during cold exposure. Dry heat loss was assessed as a differential temperature (Td) between incoming and outgoing air through the chamber for indirect calorimetry. The average Td during cold exposure normalized to surface area for ADULT mice was significantly higher than that for the AGED animals (0.0618 ± 0.0003°C/cm² and 0.0553 ± 0.0005°C/cm², respectively). Linear regression analysis showed that at the same Tco AGED mice showed lower values of Td normalized to surface area, indicating that at the same body temperature they were losing less heat than ADULT animals. It was concluded that age-related decline in cold tolerance in mice is not due to a lack of ability to reduce heat loss during cold exposure. On the contrary, AGED animals had lower heat loss in comparison with ADULT. We suggest that augmentation of heat conservation mechanisms is an adaptive response to diminishing cold-induced heat production.     

Risk of hemorrhage in the knee joint following intraarticular injections

The relative and absolute blood contents in the knee joint after intraarticular injections were determined using a biochemical joint function test. Normally, only minimal amounts of blood leak into the joint cavity, but in a few cases greater quantities were found, unnoticed at the time of injection. Intraarticular injections should be done only by a specialist.     

Systemic adverse events following intraarticular corticosteroid injections for the treatment of juvenile idiopathic arthritis: Two patients with dermatologic adverse events and review of the literature

Objectives

Intraarticular corticosteroid injections are an important part of the treatment for juvenile idiopathic arthritis due to the ability to achieve high concentration of the medication in the affected joint, while minimizing potential systemic adverse effects. There may be some systemic absorption of corticosteroids resulting in systemic adverse events. Our aim was to demonstrate the potential of adverse events due to the systemic absorption of intraarticular corticosteroids through presentation of 2 case reports, a review of our practices and a systematic review of the literature.

Methods

We reviewed the intraarticular injections performed at our 3 centers in 2010 and 2011 for the prevalence of systemic adverse events. We searched PubMed for articles in English on systemic adverse effects of intraarticular corticosteroid injection in children, using numerous keywords, as well as review articles and textbooks on juvenile rheumatoid/idiopathic arthritis up to and including December 2011.

Results

We report the development of severe acneiform rashes in 2 adolescents with juvenile idiopathic arthritis following bilateral knee intraarticular injections of triamcinolone hexacetonide. The prevalence of systemic adverse events at our centers was in 4/179 (2.2%) injections, the 2 cases reported above, 1 case of insomnia in a 2-year-old child and 1 case of cushingoid features following injection of 21 joints. While in the literature there are some reports of general “Cushing-like” appearances, there are only very few reports of specific skin and other organ/system adverse effects resulting from systemic corticosteroid absorption.

Conclusion

It is important to recognize the potential of rare adverse events that are attributable to the systemic absorption of intraarticular corticosteroids in children.     

Diet‐induced obesity significantly increases the severity of posttraumatic arthritis in mice

Objective

Obesity and joint injury are primary risk factors for osteoarthritis (OA) that involve potential alterations in the biomechanical and inflammatory environments of the joint. Posttraumatic arthritis is a frequent long‐term complication of intraarticular fractures. Obesity has been linked to primary OA and may potentially contribute to the development of posttraumatic arthritis by a variety of mechanisms. The objectives of this study were to determine whether diet‐induced obesity influences the severity of posttraumatic arthritis in mice and to examine the interrelationships between joint degeneration and serum levels of the inflammatory cytokines and adipokines that are involved in this response.

Methods

C57BL/6 mice were fed either normal chow (13% fat) or a high‐fat diet (60% fat) starting at 4 weeks of age. At 16 weeks of age, half of the mice in each group were subjected to a closed intraarticular fracture of the left knee. At 8 weeks postfracture, knee OA was assessed by cartilage and synovium histology in addition to bone morphology. Serum cytokine concentrations were determined with multiplex assays.

Results

Fractured knee joints of mice receiving a high‐fat diet showed significantly increased OA degeneration compared with nonfractured contralateral control knees, while fractured knee joints of mice receiving a low‐fat diet did not demonstrate significant differences from nonfractured contralateral control knees. A high‐fat diet increased serum concentrations of interleukin‐12p70 (IL‐12p70), IL‐6, and keratinocyte‐derived chemokine while decreasing adiponectin concentrations. Joint injury also increased IL‐12p70 concentrations in mice receiving a high‐fat diet. Systemic levels of adiponectin were inversely correlated with synovial inflammation in control limbs.

Conclusion

Diet‐induced obesity significantly increased the severity of OA following intraarticular fracture. Obesity and joint injury together can alter systemic levels of inflammatory cytokines such as IL‐12p70.

     

Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid arthritis

OBJECTIVE: To compare patients with juvenile rheumatoid arthritis (JRA) injected with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA) with respect to time to relapse. METHODS: This was a retrospective chart review of 85 patients: 51 patients with JRA who had received a joint injection with TH during the period June 2000-April 2001 and 48 patients who had received a joint injection with TA during the period May 2001-March 2002 who were followed for a minimum of 15 months, after an intraarticular steroid injection. RESULTS: The primary endpoint variable for the study was the time to relapse of the arthritis in the affected joint following an intraarticular injection. A total of 227 joints were injected, 114 with TH and 113 with TA. In the TH group the mean time to relapse (+/- SE) was 10.14 +/- 0.49 months compared to the TA group at 7.75 +/- 0.49 months (p < 0.0001) using the log-rank test. A proportional hazards (Cox) regression analysis revealed no statistical association between sex, duration of illness, or type of arthritis and relapse time. An analysis was performed on the first intraarticular injection for each patient, with the average time to relapse for all joints injected of 10.36 +/- 0.72 months for TH compared to 8.45 +/- 0.78 months for TA (p < 0.02). A further analysis of the first knee injections showed a relapse time in the TH group of 11.11 +/- 0.81 months compared to 7.95 +/- 0.95 months for TA (p < 0.008). CONCLUSION: TH offers an advantage to TA, as there is a longer duration of action leading to an improved prolonged response rate in weight-bearing joints, particularly the knees. The results suggest that TH should be the intraarticular steroid of choice, particularly for the knee joint, in patients with JRA.     

Septic arthritis caused by treatment resistant Pseudomonas cepacia.

A case of septic arthritis of the knee caused by Pseudomonas cepacia following an intraarticular corticosteroid injection in a patient with a history of osteoarthritis is presented. This is the second report of this agent causing infection in a diarthrodial joint, which proved difficult to eradicate despite in vitro antibiotic sensitivity.