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.

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.

A biophysical approach to capillary permeability.

In this preliminary report, the capillary leakage that occurs after scald injury is considered a biophysical phenomenon and is treated by sealing the "pores," or endothelial gaps, in the capillary membranes with biodegradable macromolecules of the appropriate size and shape. We have measured albumin leakage from standardized scald burns in the rat jejunum with and without variously sized fractions of intravenous macromolecules of hydroxyethyl starch (HES) used as a sealing agent. The observed reduction of albumin leakage from injured capillaries was attributed to the sealing effect. The fraction HES (Fm) with molecular weights of 100,000 to 300,000 daltons performed significantly better (p less than 0.05) as a sealing agent when compared with HES (F1) fraction molecular weights of 300,000 to 3.4 million daltons, HES (Fs) molecular weight less than 50,000 daltons, and two control groups receiving the intravenous Ringer's lactate solution or serum albumin 5%. This capillary sealing phenomenon was shown to be independent of colloid osmotic pressure effect. It is believed to be related to the size and the shape of the noncharged macromolecules.

Exercise and drill boards for surgical training. 10 year experience with a knot-tying board.

For the past 10 years, the knot-tying board has served many students of surgery as a helpful teaching tool for the mastery of surgical knots. The early acquisition of basic surgical techniques by surgical trainees as dry runs, exercises and practice before in vivo trials is especially needed because of our present medical and legal atmosphere. The increasing inaccessibility of animal surgery to surgical students and trainees gives the practice or drill boards a more important and necessary role than in the past. With this in mind, we hope that the Operation Drill Board model we have developed will be as useful to students of surgery as the knot-tying board has been over the past 10 years.

Mallory-Weiss syndrome. A changing clinical picture.

A retrospective study of 18 episodes of upper gastrointestinal (UGI) bleeding secondary to Mallory-Weiss syndrome occuring in 16 patients is presented. Reported cases published since 1969 have been summarized and compared with earlier collected series. It is evident that the clinical spectrum, prognosis, and opinion regarding etiology and treatment of the syndrome have changed in the last decade. Increased awareness of gastroesophageal lacerations secondary to emesis as well as other causes of significantly increased intraesophagogastric pressures, and widespread utilization of fiberoptic endoscopy have resulted in identification of Mallory-Weiss syndrome with increasing frequency. Less severe lacerations which are healing with medical therapy are being recognized. It is recommended that endoscopy by performed in all cases of UGI hemorrhage and that patients with Mallory-Weiss syndrome be managed medically unless hemorrhage is massive or persistent since nearly three of four patients can be successfully treated without operation.

The surface tension of upper airway secretions in patients with and without respiratory disease.

The alveolar-arterial oxygen partial pressure (PAaO2) difference and surface tension of upper airway secretions (UASST) were simultaneously measured in 33 intubated patients. Patients without respiratory disease had UASST and PAaO2 gradients significantly lower than those with chronic obstructive lung disease. Patients in respiratory failure had UASST and PAaO2 gradients significantly higher than when they were out of failure. Correlation of UASST with PAaO2 was good (r = 0.81). These findings demonstrate that UASST closely correlate with the severity of pulmonary disease and suggest that their measurement may be a simple, clinically applicable method of assessing alveolar surfactant function.