Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size.

Open-chest sheep underwent 90 minutes' occlusion of the diagonal branch of the left anterior descending coronary artery, followed by vented cardiopulmonary bypass. After 30 minutes of cardioplegic arrest, simulating distal anastomoses, the occlusion on the coronary artery branch was released. Controlled reperfusion (40 to 50 mm Hg, 135 to 150 ml/min) for the first 20 minutes was delivered at the aortic root with either unmodified whole blood (control, n = 7) or blood passed through leukocyte filters (filters, n = 7). Serial measurements were made during 3 additional hours reperfusion off cardiopulmonary bypass. During ischemia, the major determinants of infarct size, which include area at risk, collateral myocardial blood flow, and rate-pressure product were not significantly different between groups. Overall, during reperfusion, mean left ventricular stroke work index in the filter group was greater than in the control group (28.7 +/- 5.8 versus 12.6 +/- 6.4 x 10(3) erg/gm, p less than 0.05), as was mean rate of rise of left ventricular pressure (1900 +/- 260 versus 1348 +/- 279 mm Hg/sec, p less than 0.05). Myocardial blood flow to the area at risk at 3 1/2 hours of reperfusion in the filter group was also significantly better than in the control group (0.57 +/- 0.15 versus 0.27 +/- 0.05 ml/min/gm, p less than 0.05), as was necrotic area as a percentage of area at risk (40% +/- 6% versus 70% +/- 5%, p less than 0.05). These results demonstrate amelioration of myocardial stunning and the no-reflow phenomenon, as well as decreased infarct size. We conclude that controlled reperfusion with leukocyte-depleted blood is superior to whole-blood reperfusion for the surgical treatment of acute regional ischemia.     

The accuracy and reliability of a novel handheld dynamic indentation probe for analysing articular cartilage

This study investigates the accuracy and reliability of a novel handheld indentation system designed to ascertain the dynamic biomechanical properties of articular cartilage. A series of standard elastomers were assessed with both the handheld indentation system and a bench-top dynamic indentation system to assess the accuracy of the instrument. Interoperator and intraoperator experiments were undertaken to investigate the reliability of the system when used by an individual operator and by five different operators. Intraclass coefficients (Rho) were derived using a random effects model. The system was then used to ascertain the topographical variation in the shear moduli and phase lag of articular cartilage across normal ovine tibial plateaux. The system was shown to be highly accurate (R2 = 0.97), and had excellent reliability when measuring the dynamic shear modulus of articular cartilage (interoperator Rho = 0.75, intraoperator Rho = 0.79). Measurement of static shear modulus was less reliable (interoperator Rho = 0.15, intraoperator Rho = 0.52), but may be improved by monitoring the load applied to the instrument by the operator. The instrument was used to differentiate between different regions of cartilage and generated a topographical map of an ovine tibial plateau. The cartilage located beneath the menisci was 200-500% stiffer than the cartilage that was not covered by the menisci, while the phase lag was almost constant (10+/-2 SD) over the entire tibial plateau. The system was shown to be an accurate and reliable tool for rapidly assessing the dynamic biomechanical properties of articular cartilage, while being small enough to be used arthroscopically.     

Hemochromatosis mutations in the general population: iron overload progression rate

The progression rate of iron overload in hereditary hemochromatosis in individuals in the general population is unknown. We therefore examined in the general population iron overload progression rate in C282Y homozygotes. Using a cohort study of the Danish general population, The Copenhagen City Heart Study, we genotyped 9174 individuals. The 23 C282Y homozygotes identified were matched to 2 subjects each of 5 other HFE genotypes with respect to sex, age, and alcohol consumption. As a function of biologic age, transferrin saturation increased from 50% to 70% from 25 to 85 years of age and from 70% to 80% from 35 to 80 years of age in female and male C282Y homozygotes, respectively. Equivalently, ferritin levels increased from 100 to 500 µg/L and decreased from 800 to 400 µg/L in female and male C282Y homozygotes. As a function of 25 years follow-up irrespective of age, transferrin saturation and ferritin levels increased slightly in male and female C282Y homozygotes. None of the C282Y homozygotes developed clinically overt hemochromatosis. In conclusion, individuals in the general population with C282Y homozygosity at most demonstrate modest increases in transferrin saturation and ferritin levels, and clinically overt hemochromatosis is rare. Therefore, C282Y homozygotes identified during population screening, and not because of clinically overt hemochromatosis, at most need to be screened for manifestations of hemochromatosis every 10 to 20 years. (Blood. 2004;103: 2914-2919)      

Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats

Background:

Osteoporosis is characterized by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed and rates of implant failure are high with few biological treatment options available. This study aimed to determine whether a single dose of bone morphogenetic protein-7 (BMP-7) in a collagen/carboxy-methyl cellulose (CMC) composite enhanced fracture healing in an osteoporotic rat model.

Materials and Methods:

An open femoral midshaft osteotomy was performed in female rats 3 months post-ovarectomy. Rats were randomized to receive either BMP-7 composite (n = 30) or composite alone (n = 30) at the fracture site during surgery. Thereafter calluses were collected on days 12, 20 and 31. Callus cross-sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point.

Results:

There were statistically significant increases in bone mineral density and callus cross-section area at all time points in the BMP-7 group as compared to controls and biomechanical readings showed stronger bones at day 31 in the BMP-7 group. Histological and radiographic evaluation indicated significant acceleration of bony union in the BMP-7 group as compared to controls.

Conclusion:

This study demonstrated that BMP-7 accelerates fracture healing in an oestrogen-deficient environment in a rat femoral fracture healing model to scientific relevance level I. The use of BMP-7 composite could offer orthopedic surgeons an advantage over oestrogen therapy, enhancing osteoporotic fracture healing with a single, locally applied dose at the time of surgery, potentially overcoming delays in healing caused by the osteoporotic state.     

The Orthopaedic Research Institute-Ankle Strength Testing System: inter-rater and intra-rater reliability testing

Achilles tendinosis is a degenerative overuse tendinopathy involving the primary ankle plantarflexors, namely the soleus and gastrocnemius muscles forming the tendo Achilles. The Orthopaedic Research Institute-Ankle Strength Testing System (ORI-ASTS) was designed to record objective measurements of force generated with a resisted ankle plantarflexion test. Testing normal subjects (n=6) was used to establish the reliability of the ORI-ASTS for measuring ankle plantarflexion force. Testing patients with Achilles tendonitis (n=5) over time and comparing Achilles tendon analogue pain scores to ankle plantarflexion force measurements was used to assess the validity of the ORI-ASTS for monitoring progression of Achilles tendinopathy. Inter-rater reliability of the ORI-ASTS with normal subjects was excellent, with single measure intraclass correlation coefficients (ICC) for right mean peak force of 0.92, left mean peak force of 0.96, right mean total force of 0.89, left mean total force of 0.91. The ORI-ASTS also had excellent intra-rater reliability for normal subjects with the following single measure ICC scores: right mean force 0.96, left mean force 0.92, right mean total force 0.97, left mean total force 0.92. The relative technical errors of measurement were calculated from these results, and ranged from 1.0% to 2.7%. Testing patients with Achilles tendinosis (n=5), and comparing analogue activity pain scores to ORI-ASTS testing demonstrated a strong negative relationship between the two parameters (Spearman Rho -0.87 to -1.0, Kendall tau b -0.82 to -1.0). The relationship was statistically significant at the p=0.01 level for two of the five patients. The ORI-ASTS shows excellent reliability for testing ankle plantarflexor force, and appears valid for objectively assessing and monitoring patients with Achilles tendinosis.     

Ten genetic polymorphisms in bladder cancer.

Data are presented on a group of cases of primary carcinoma of the bladder, detailing red cell surface blood group antigenic phenotypes, serum haptoglobin phenotypes, and some red cell isoenzyme phenotypes. Account is taken of the stage of the disease at presentation. The results are compared with corresponding phenotype frequencies in groups of presumed healthy persons originating either in Yorkshire or County Durham. Differences in relative incidences were found in the haptoglobin, phosphoglucomutase (PGM), and some other systems. These are both differences between all cases and controls and between particular stages at presentation and controls.     

The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy

AIM: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA). METHODS: Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis. RESULTS: MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP. CONCLUSIONS: Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA.