Association of patella alta with worsening of patellofemoral osteoarthritis-related structural damage: data from the Osteoarthritis Initiative.

OBJECTIVES: To determine the association between Insall-Salvati ratio (ISR), a measure of patella alta, and worsening of Magnetic Resonance Imaging (MRI)-based osteoarthritis (OA)-related patellofemoral joint structural damages over 24-month in participants of the Osteoarthritis Initiative (OAI). DESIGN: Using weighted random sampling method, we selected a sample of 500 knees (from 1,677 knees with available baseline and 24-months MRI OA Knee Score (MOAKS) measurements), which is OAI-representative regarding knee OA-related factors (i.e., baseline age, sex, body mass index (BMI), and radiographic Kellgren-Lawrence grading). The ISR was measured in all enrolled knees using baseline sagittal 3T-MRI plane by three radiologists. Baseline and 24-month MOAKS variables for patellofemoral bone marrow lesions (BMLs), cartilage damages, and osteophytes were extracted, and the associations between ISR and 24-month worsening of these 3T-MRI features were evaluated using multivariable regression models. After computing receiver operating characteristic curves, the optimal cutoff point of ISR for indicating worsening of patellofemoral OA was determined. P-values were adjusted for multiple comparisons and false discovery rate (FDR) adjusted P-values were reported. RESULTS: In this longitudinal analysis, 24-month worsening of BML (odds ratio [OR] (95% confidence interval [95% CI]):11.18 (3.35-39.6), adjusted-p-value:<0.001) and cartilage scores (OR:7.39 (1.62-34.71), adjusted-p-value:0.042) in lateral patella was associated with higher baseline ISR. However, higher ISR was not statistically associated with medial patellar or medial and lateral trochlear BML or cartilage scores worsening. We determined the optimal cutoff point of ISR≥1.14 (95% CI: 1.083-1.284) for predicting lateral patellofemoral OA-related structural damages worsening over 24-months (sensitivity:73.73%; specificity: 66.67%). CONCLUSIONS: Given the uncertainly surrounding the results, our overall findings suggest that ISR could be considered as a predictor of lateral patellofemoral OA-related structural damages worsening with the optimal cutoff point of ≥1.14 using knee sagittal MRI measurements.

Role of physical activity in cartilage damage progression of subjects with baseline full-thickness cartilage defects in medial tibiofemoral compartment: data from the Osteoarthritis Initiative.

OBJECTIVE: To assess the association between physical activity and cartilage damage progression in medial tibiofemoral compartment (MTFC) using 2-year follow-up magnetic resonance imaging (MRI) in subjects with denuded areas of subchondral bone (dABs) at the central weight-bearing medial femur (cMF) at baseline MRI examination. METHODS: One hundred subjects from the Osteoarthritis Initiative (OAI) progression cohort with dABs at the cMF at 3T MRI at baseline (51% men; mean age 62.2 years, range 45-79) were included. Sagittal 3D dual-echo steady-state with water excitation images were used to assess 2-year MTFC cartilage change. Associations between 2-year average Physical Activity Scale for the Elderly (PASE) and 2-year MTFC cartilage change were assessed by linear regression analysis. Subgroup analyses were performed. RESULTS: No associations between PASE and 2-year MTFC cartilage change were observed in the entire cohort. Similarly, in the subgroup with cartilage loss during the 2 years, the non-refuted confidence intervals for the regression coefficients were tightly clustered around the null value (regression coefficients for: mean cMF.ThCtAB = -0.00059; 98.75% CI: -0.00130 to 0.00012), cMF.dAB% = 0.02176; 98.75% CI: -0.02514 to 0.06865, Mean MT.ThCtAB = -0.00013; 98.75% CI: -0.00064 to 0.00038, MT.dAB% = 0.02543; 98.75% CI: -0.01485 to 0.06571. CONCLUSION: In the entire group of subjects with dABs at the cMF at baseline, no association between physical activity and 2-year MTFC cartilage change was detected. Due to the limited sample size of our study, small-sized effects may not have been detected in our study.

Long term use of analgesics and risk of osteoarthritis progressions and knee replacement: propensity score matched cohort analysis of data from the Osteoarthritis Initiative.

OBJECTIVES: To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). DESIGN: Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic +) and 173 referent (Analgesic -) subjects were included. Analgesic + and - subjects had analgesics in all and none of their visits, respectively. Analgesic + and - subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic + and - subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. RESULTS: Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic + and 15 among Analgesic - subjects (P = 0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic + and 12 among Analgesic - subjects (P = 0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic + subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. CONCLUSIONS: Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR.

Association of mucoid degeneration of anterior cruciate ligament with knee meniscal and cartilage damage.

OBJECTIVE: To assess the prevalence of anterior cruciate ligament (ACL) mucoid degeneration in patients referred for routine knee magnetic resonance (MR) imaging, and its association with age and structural joint damage. METHOD: Four independent radiologists assessed 413 consecutive knee MR examinations for the presence of a normal or ruptured ACL, or ACL mucoid degeneration. Knees with ACL mucoid degeneration were frequency matched by age, sex, and MR field strength with consecutive control knees with a normal ACL (1:2 ratio). Differences in meniscal and cartilage damage of the tibiofemoral compartments, as determined by the Whole-Organ MR Imaging Score (WORMS) system, were compared by Mann-Whitney U tests. Multivariable logistic regression analysis identified the association of ACL mucoid degeneration with severe MTFC cartilage damage (WORMS≥5). RESULTS: Patients with ACL mucoid degeneration (n = 36; 36% males; median age 55.5 years, range: 26-81) were older than patients with a normal (P < 0.001) or ruptured ACL (P < 0.001), without sex predilection (P = 0.76), and were more frequently diagnosed at 3 T (12%) compared to 1.5 T (2%). Knees with ACL mucoid degeneration had statistically significantly more medial meniscal (P < 0.001) and central and posterior medial tibiofemoral compartment (MTFC) cartilage (P < 0.001) damage compared with control knees (n = 72), but there were no differences in patients ≤50 years (P = 0.09 and 0.32, respectively). In multivariable logistic regression, severe MTFC cartilage damage (WORMS≥5) was significantly associated with ACL mucoid degeneration (odds ratio 4.09, 95% confidence interval 1.29-12.94, P = 0.016). CONCLUSION: There is a strong association between ACL mucoid degeneration and cartilage damage in the central and posterior MTFC, especially in patients >50 years.

Medium molecular weight pentastarch reduces reperfusion injury by decreasing capillary leak in an animal model of spinal cord ischemia.

PURPOSE: The medium molecular weight fraction of pentastarch (HES-Pz) has been shown to decrease reperfusion injury to myocardium and brain by reducing capillary leak. This study was undertaken to assess the effects of HES-Pz on neurologic function, microvascular permeability, and spinal cord infarction after temporary aortic cross-clamping in a rabbit model. METHODS: In 30 New Zealand White rabbits, a snare occlusion device was placed around the infrarenal aorta and tunneled into a subcutaneous position. Animals were allowed to recover for 48 hours and were randomized into three groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal for 21 minutes. Immediately after unclamping, animals received an intravenous infusion of 4% of their estimated blood volume of one of the following solutions: normal saline solution (NS; group 1); 6% standard hydroxyethyl starch (HES), molecular weight 10 to 3400 kD (group 2); and 6% HES-Pz, molecular weight 100 to 1000 kD (group 3). During 5 days of observation, neurologic recovery was graded by an independent observer using the Tarlov scale. Animals were then killed and their spinal cords harvested for histologic examination using hematoxylin-eosin and 2,3,5-triphenyltetrazolium chloride staining. In a separate group of animals (n = 15), the occurrence of spinal cord capillary permeability after NS, HES, and HES-Pz infusions was evaluated by spectrophotometric analysis of extravasated Evans blue. RESULTS: Complete paraplegia and marked histologic evidence of spinal cord cellular injury were seen in 90% of group 1 (NS) and in 78% of group 2 (HES). Treatment with HES-Pz (group 3) resulted in full neurologic recovery in 89% of animals (p < 0.05) and a threefold reduction of extravasated Evans blue compared with controls (p < 0.05). CONCLUSIONS: These results indicate that microvascular hyperpermeability plays an important role in reperfusion injury to the spinal cord. Treatment with HES-Pz reduced the capillary permeability, neuron membrane injury, and incidence of paraplegia after reperfusion of ischemic spinal cord in a rabbit model.

Monitoring of rat islet allografts with dithizone after induction of donor specific transplant tolerance by intrathymic administration of soluble alloantigens.

Transplantation of whole pancreas or pancreatic islets remains a promising approach to treatment of diabetes mellitus. Since there is no efficient method presently known for in vivo detection of pancreatic islet rejection, we have utilized dithizone [DTZ] to monitor the survival of transplanted islet allografts following the induction of tolerance by a new strategy of deliberate introduction of donor antigens into the adult thymus. In this study, we examined the morphology of islet allografts in vivo and in vitro following pretreatment with intrathymic (IT) inoculation of 2 mg soluble Ag obtained from 3M KCl extracts of resting T-cells with or without ALS immunosuppression in the WF-to-Lewis combination. Fresh isolated rat islets stained pink 3-5 minutes following exposure to medium containing 0.12 mM DTZ solution in DMSO. Intravenous (i.v.) injection of DTZ solution into unmodified recipients of islet allografts that had rejected their grafts showed massive degranulation of islets which did not stain pink with DTZ. This was confirmed by microscopic finding of fibrosis and lymphocytic infiltration. In contrast, i.v. injection of DTZ solution into long-term recipients of islet allografts at 50, 100, and 150 days after transplantation showed viable islet cells which stained crimson red with DTZ and the findings were confirmed with microscopic sections. This study demonstrates that DTZ is an effective means of in vivo and in vitro identification of transplanted pancreatic islets and suggests that this strategy may have potential clinical application in the diagnosis of the pancreatic islet rejection.

Attenuation of microvascular permeability dysfunction in postischemic striated muscle by hydroxyethyl starch.

We examined the effect of hydroxyethyl starch macromolecule (HES-Pz) pretreatment on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate dextran 150 (FITC-Dx 150) was measured as an index of microvascular transport. After determination of baseline data, the muscle was made ischemic for 4 hr by clamping the vascular pedicle and subsequently reperfused for 2 hr. In control animals not subjected to ischemia, clearance of FITC-Dx 150 remained constant throughout the experimental 7-hr period. In saline-treated animals, ischemia-reperfusion increased the clearance of FITC-Dx 150 from 1.8 +/- 0.3 to 9.7 +/- 1.0 microliters/15 min/g by the end of the reperfusion period. Pretreatment with HES-Pz, at a concentration of 6% in a volume of saline equivalent to 10% of blood volume, significantly attenuated the microvascular dysfunction produced by ischemia-reperfusion. The mean ratio of postischemic to baseline clearance of FITC-Dx 150 was 1.28 +/- 0.07 (mean +/- SE) for samples taken from the 30th to the 120th min of reperfusion at 15 intervals. Our data support a beneficial effect of HES-Pz on microvascular transport of macromolecules. The role of leukocyte-endothelium adhesion as an underlying mechanism explaining these results was studied by evaluating the effect of HES-Pz on the ability of thrombin-stimulated human umbilical vein endothelial cells (HUVECs) to bind neutrophils. These experiments demonstrated that thrombin-treated HUVECS bound 229% more indium-111-labeled neutrophils than did similarly stimulated HUVECS treated with HES-Pz (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hydroxyethyl starch macromolecule and superoxide dismutase effects on myocardial reperfusion injury.

Myocardial reperfusion injury may be due to biophysical changes (e.g., endothelial cell junctional separations), as well as biochemical mechanisms (e.g., oxygen free radical activity). Superoxide dismutase (SOD), a free radical scavenger, may be effective in reducing chemical injury. Fractions of hydroxyethyl starch (HES-Pz), a large macromolecule, have been shown to decrease microvascular permeability associated with reperfusion-induced biophysical alterations. A comparison of SOD to HES-Pz was performed using a canine model of 1-hour left anterior descending coronary artery (LAD) clamping followed by 24 hours of reperfusion. Amounts of the test solution equal to 10% of the dog's blood volume were administered intraatrially to the animals just before release of the LAD clamp. Six dogs received Ringer's lactate, 7 were given 600,000 IU of SOD, 13 received 6% HES-Pz, and 9 were given SOD and HES-Pz. The ratio of infarct to area at risk was 20 +/- 3% in the control dogs receiving Ringer's lactate, 16 +/- 4% in animals receiving SOD alone (p = NS), 6 +/- 3% in dogs receiving HES-Pz alone (p less than 0.05), and 8 +/- 3% in dogs given a combination of SOD and HES-Pz (p less than 0.05). HES-Pz alone and with SOD significantly reduced reperfusion injury, although addition of SOD to HES-Pz did not have an additive effect. Appropriate-sized macromolecules may act by reducing ischemia-induced microvascular permeability.

Hydroxyethyl starch macromolecules reduce myocardial reperfusion injury.

We assessed the value of a fraction of hydroxyethyl starch (HES Pz) in reducing the myocardial reperfusion injury in a canine open-chest model in which 1 hour of left anterior descending coronary artery occlusion was followed by 24 hours of reperfusion. Three treatment infusions (5% of blood volume) were compared: Ringer's lactate, serum albumin, and HES Pz (70% of the macromolecules between 100,000 and 1,000,000 d). When compared with Ringer's lactate and albumin, HES Pz significantly reduced the ratio of 24-hour infarct size to pretreatment area at risk (3% vs 19% and 16%, respectively) and myocardial water content (0.5% vs 3% and 1%). Potassium content differences between injured and normal myocardium were significantly less in the infarct regions of animals receiving HES Pz. In the canine model, HES Pz reduced 1-hour myocardial ischemia reperfusion injury significantly.

Macromolecules reduce abnormal microvascular permeability in rat limb ischemia-reperfusion injury.

We studied the effect of iv administration of biodegradable macromolecules on microvascular permeability after ischemia-reperfusion injury in a rat gastrocnemius model. After 2 h of tourniquet ischemia of the rats' hind limb, groups of animals were given iv lactated Ringer's solution (RL), serum albumin 5%, or varying MW fractions of biodegradable macromolecules of hydroxyethyl starch (HES), glycogen, and dextran. At the conclusion of the 24-h reperfusion period, the rat gastrocnemius muscles were collected. Water and K+ differences between the ischemic and control muscles were compared. Rats given a 100,000 to 300,000-dalton fraction of HES had significantly decreased water content (5.1 +/- 3.4%) when compared to rats receiving RL (8.3 +/- 2.2, p less than .01), less than 100,000 dalton HES (8.3 +/- 3.2, p less than .05), less than 300,000 glycogen (7.9 +/- 2.5, p less than .01), or dextran 150,000 (8.3 +/- 1.5, p less than .05). Rats given 100,000 to 300,000-dalton HES also had significantly higher ischemic muscle K+ content as compared to the nontourniquet control (difference 14.2 +/- 9.7 mEq/g) than rats receiving any of the other solutions (range 32.5 to 39.3) except the 300,000 to 1,000,000-dalton fraction of HES. Regression analysis comparison of K+ difference to the histologic evaluation of the muscles on the criteria of polymorphonuclear infiltration and interstitial edema (0, best; 3, worst) had a Pearson correlation coefficient of r = .73. Reduction of abnormally increased microvascular permeability may be accomplished by the iv use of appropriate sized biodegradable macromolecules.