Addressing the question of the effect of RBC storage on clinical outcomes: the Red Cell Storage Duration Study (RECESS) (Section 7).

The question of whether storage of red blood cells (RBCs) alters their capacity to deliver oxygen and affects patient outcomes remains in a state of clinical equipoise. Studies of the changes which occur while RBCs are stored have led to several physiologically plausible hypotheses that these changes impair RBC function when the units are transfused. Although there is some evidence of this effect in vivo from animal model experiments, the results of several largely retrospective patient studies have not been consistent. Some studies have shown an association between worse clinical outcomes and transfusion of RBC which have been stored for longer periods of time, while others have found no effect. Three multicenter, randomized, controlled trials have been developed to address this important, but currently unanswered, question. Two clinical trials, one in low birth weight neonates and the other in intensive care unit patients, are enrolling subjects in Canada (the Age of Red Blood Cells in Premature Infants; the Age of Blood Study). The third trial, which is being developed in the United States, is the Red Cell Storage Duration Study (RECESS). This is a multicenter, randomized, controlled trial in which patients undergoing complex cardiac surgical procedures who are likely to require RBC transfusion will be randomized to receive RBC units stored for either 10 or fewer days or 21 or more days. Randomization will only occur if the blood bank has enough units of RBC of both storage times to meet the crossmatch request; hence, subjects randomized to the 21 day arm will receive RBC of the same storage time as they would have following standard inventory practice of "oldest units out first". The primary outcome is the change in the Multiple Organ Dysfunction Score (MODS), a composite measure of multiorgan dysfunction, by day 7. Secondary outcomes include the change in the MODS by day 28, all-cause mortality, and several composite and single measures of specific organ system function. The estimated total sample size required will be 1434 evaluable subjects (717 per arm).

Dynamic lateral patellar tilt in the anterior cruciate ligament-deficient knee. A magnetic resonance imaging analysis.

An open-configuration magnetic resonance imaging scanner was used to document patellar tracking abnormalities in 11 anterior cruciate ligament-injured knees. The contralateral normal knees were used as controls. Images were obtained with the quadriceps muscles at rest (knee flexion at 40 degrees, 25 degrees, and 10 degrees) and with the quadriceps muscles contracted (knee flexion at 40 degrees and 25 degrees). When the quadriceps muscles were at rest there were no differences in patellar alignment between the anterior cruciate ligament-injured knees and the contralateral normal knees. When the quadriceps muscles were maximally contracted at 40 degrees of flexion, the patellae of the anterior cruciate ligament-injured knees tilted laterally 3.6 degrees relative to the resting state. When the quadriceps muscles were contracted at 25 degrees of flexion, the patellae of the anterior cruciate ligament-injured knees tilted laterally approximately 4 degrees relative to the resting state. Quadriceps-active lateral patellar tilt at 25 degrees of flexion was greater in the anterior cruciate ligament-injured knees than in the contralateral normal knees, and it correlated with instrumented measurements of anterior tibial translation. Dynamic lateral patellar tilt during open kinetic chain exercises and during other activities that produce anterior tibial translation may contribute to extensor mechanism dysfunction in the anterior cruciate ligament-injured knee.

Hamstring tendon grafts for reconstruction of the anterior cruciate ligament: biomechanical evaluation of the use of multiple strands and tensioning techniques.

BACKGROUND: Our hypothesis that multiple, equally tensioned strands of hamstring graft used for reconstruction of the anterior cruciate ligament are stronger and stiffer than ten-millimeter patellar ligament grafts was tested biomechanically with use of tendons from cadavera. METHODS: In the first part of the study, we measured the strength and stiffness of one, two, and four-strand hamstring grafts, from fresh-frozen cadaveric knees, that had been tensioned equally when clamped. In the second part of the study, we compared four-strand grafts to which tension had been applied by hand and then clamped with similar grafts to which tension had been applied with weights and then clamped. The grafts for the two experiments were obtained from thirty-four paired and ten unpaired knees. We also studied the effects of cooling on the biomechanical properties of grafts by comparing patellar ligament grafts tested at 13 degrees Celsius with those tested at room temperature. RESULTS: Two equally tensioned gracilis strands had 185 percent of the strength and 210 percent of the stiffness (1550+/-428 newtons and 336+/-141 newtons per millimeter, respectively) of one gracilis strand (837+/- 138 newtons and 160+/-44 newtons per millimeter, respectively). Two equally tensioned semitendinosus strands had 220 percent of the strength and 220 percent of the stiffness (2330+/-452 newtons and 469+/-185 newtons per millimeter, respectively) of one semitendinosus strand (1060+/-227 newtons and 213+/-44 newtons per millimeter, respectively). Four combined strands (two gracilis strands and two semitendinosus strands) that were equally tensioned with weights and clamped had the additive tensile properties of the individual strands. With the numbers available, four combined strands that were manually tensioned and clamped were not found to be significantly stronger or stiffer than two semitendinosus strands that were equally tensioned with weights (p>0.07). CONCLUSIONS: Four combined strands that were equally tensioned with weights and clamped were stronger and stiffer than all ten-millimeter patellar ligament grafts that have been described in previous reports. All strands of a hamstring graft must be equally tensioned for the composite to have its optimum biomechanical properties. CLINICAL RELEVANCE: Because of the well recognized donor-site morbidity associated with the use of patellar ligament grafts for reconstruction of the anterior cruciate ligament, multiple-strand hamstring-tendon grafts have become an increasingly popular choice. Our data demonstrate that equally tensioned four-strand hamstring-tendon grafts have initial tensile properties that are higher than those reported for ten-millimeter patellar-ligament grafts; thus, from a biomechanical point of view, they seem to be a reasonable alternative.

A survey of pediatric malignancy in West Virginia.

The occurrence of malignancy in the pediatric age group is an uncommon but serious event. Since little data are available on the extent, nature or referral patterns of childhood cancer in West Virginia, we conducted a survey of 782 primary care physicians and 17 regional referral centers. The results showed that 249 cases of malignancy in the pediatric age group were reported and that 68% of children with newly diagnosed childhood malignancy were referred to institutions within West Virginia. We conclude that the incidence and distribution of types of malignancy in childhood in West Virginia parallels that of the nation, although there is some regional variation within the state.

Curing children with leukemia in West Virginia.

Leukemia is the most common cancer in childhood with acute lymphoblastic leukemia (ALL) the most common subtype. While once uniformly fatal, today leukemia is a highly curable disease. To determine the outcomes of children with acute lymphoblastic leukemia in West Virginia, we performed a retrospective analysis of the results of treatment of children and adolescents with B-lineage ALL diagnosed between 2/86 and 1/91 and treated by the pediatric oncology teams at Morgantown or Charleston. Forty-one children with B-lineage ALL were identified and treated by a uniform protocol. Twenty-nine (71%) have remained disease-free for more than two years off therapy and are considered cured. Of the 10 patients who relapsed, five have now been off rescue therapy for greater than two years and are likely to be cured. Thirty-five of the original cohort of 41 children are alive and disease-free yielding an overall survival of 85%. The results of treatment of childhood leukemia in West Virginia are comparable to national data. Children with ALL diagnosed and treated by pediatric oncology teams in West Virginia have a very good chance of being cured.

Anterior cruciate ligament reconstruction using gracilis and semitendinosus tendons. Comparison of through-the-condyle and over-the-top graft placements.

Eighty-seven patients had anterior cruciate ligament reconstruction using one-limbed gracilis and semitendinosus tendon graft. No extraarticular or associated ligamentous procedures were performed. A 44-patient subgroup was alternated on an every-other-case basis between 2 graft placements, either over the top or through the femoral condyle; 64 patients (32 of each type) returned for complete evaluations. Average followup was 2.9 years. Groups were similar in age, gender, injury chronicity, number of meniscectomies, and preoperative activity levels. No statistical differences between groups were seen in overall knee rating, range of motion, KT-1000 arthrometer measurements, isokinetic muscle testing, or one-legged hop test. Injured minus normal anterior laxity at 89 N was 2.1 +/- 2.0 mm. Isokinetic testing demonstrated an average 95% normal knee extension strength and 106% normal flexion strength, measured at 60 deg/sec. Average hop index was 95%. Eight of 64 patients evaluated demonstrated injured minus normal differences of 4.5 mm or greater. Three of 8 had frankly positive 2+ and 5 had 1+ pivot shifts; however, 4 of these returned fully to sports, and 4 returned with modifications. Overall, 55 of 64 patients returned to preinjury sports.

Anterior cruciate ligament graft fixation. Comparison of hamstring and patellar tendon grafts.

This study assessed the tensile properties of hamstring and patellar tendon anterior cruciate ligament reconstructions in older cadaveric knees (age range, 48 to 79 years). Mechanical testing to failure was conducted by translating the tibia anteriorly at 1 mm/sec with the knee in 20 degrees of flexion. The strongest gracilis-semitendinosus graft fixation technique (103% of intact anterior cruciate ligament) had the tendons doubled and secured with soft tissue washers (P < 0.01). However, all reconstructions using gracilis-semitendinosus grafts were significantly less stiff than the intact anterior cruciate ligament specimens regardless of fixation technique (P < 0.01). The highest strength patellar tendon graft fixation technique (84% of intact anterior cruciate ligament) was obtained with a combination interference screw and suture technique. The difference in stiffness between a patellar tendon graft and an intact anterior cruciate ligament was not significant when interference screws were placed at both ends of the graft (P > 0.05). Both types of grafts failed most often on the tibial side. With appropriate fixation, both grafts approximated the intact anterior cruciate ligament in strength, but only patellar tendon grafts secured with interference screws were comparable in stiffness.

The use of hamstring tendons for anterior cruciate ligament reconstruction. Technique and results.

We feel that some of the current prejudice against use of hamstring tendon grafts for ACL reconstruction has not been justified if one critically reviews the literature. In this article, we have tried to provide the reader with our current indications, present our current surgical technique, and review some of the outcome studies involving use of the hamstring tendons for ACL reconstruction. We also feel that some of the poor results of hamstring tendon ACL reconstructions previously reported resulted from the use of inadequate strength grafts (single-stranded grafts) and lack of rigid fixation on both ends of the graft (usually secondary to inadequate graft length). We feel that the technique described in this article addresses both of these issues. It is our clinical impression that, in appropriately selected patients, this technique produces stability and functional outcome similar to that obtained with patellar tendon grafts but results in less postoperative pain, a quicker return of quadriceps muscle function, and less donor site morbidity.

Measurement of anterior-posterior displacement of the knee. A comparison of the results with instrumented devices and with clinical examination.

Thirteen subjects who had normal knees and fifteen patients who had a chronic rupture of the anterior cruciate ligament were tested in order to compare the measurements of tibiofemoral displacement as recorded by four commercial devices: the Acufex knee-signature system, the Genucom knee-analysis system, the Medmetric KT-1000 arthrometer, and the Stryker knee-laxity tester. Anterior and posterior displacement were measured at forces of eighty-nine newtons (twenty pounds) and 133 newtons (thirty pounds). We found significant differences in reproducibility of measurement among the devices. The Acufex, Medmetric, and Stryker devices had more reproducible measurements, and they could be used to identify 80 to 90 per cent of the normal subjects and anterior cruciate-deficient patients. The Genucom device had poorer reproducibility of measurement, and it tended to register greater differences in displacement between the right and left knees of normal subjects.

Early changes in gait and maximum knee torque following knee arthroplasty.

Fourteen knees in 11 individuals were studied before knee arthroplasty and at three and six months following surgery. Eleven of these knees were further evaluated at 12 months following surgery. At each evaluation, kinematic, electromyographic, and force plate data were gathered during level walking. Maximum knee extension and flexion torques were also determined. The greatest improvement in gait was noted in the first three postoperative months when velocity increased 13% and stride length increased 14%. After six months gait changes were negligible. Maximum knee torques in the osteoarthritic population were decreased at three months, then returned to preoperative levels at six months. In the rheumatoid population, maximum knee torques steadily increased up to six months following surgery. Gait abnormalities that persist at six months and beyond following knee arthroplasty appear to be most related to the presence of arthritis in joints other than in the operated knee(s).

The young athlete's knee: recent advances.

The understanding and treatment of the young athlete's knee has improved and continues to do so as arthroscopy and good long-term follow-up studies guide the process. In the management of epiphyseal fractures about the knee the presence of associated ligament injury and the high likelihood of a growth plate injury is now well documented. In the management of ligament injuries and internal derangements, arthroscopy has profoundly changed diagnosis and treatment. Pathology can be precisely identified and the appropriate treatment initiated to preserve an athletic career and possibly prevent degenerative arthritis in adulthood. Lastly, patellofemoral pain continues to be a difficult problem to treat, but a more scientific approach is evolving. This has been facilitated by a better understanding of the varied etiologies for anterior knee pain, and a trend away from classifying all such conditions as chondromalacia.

Effect of L-asparaginase administration on coagulation and platelet function in children with leukemia.

The use of L-asparaginase during remission induction in patients with leukemia is associated with coagulation abnormalities, which may present either as thrombosis or hemorrhage. However, because of the multiple pharmacologic and hematologic variables present in these patients, the exact contribution of L-asparaginase to these coagulation abnormalities is unclear. We studied platelet function and plasma coagulation parameters in 12 pediatric patients with acute lymphoblastic leukemia (ALL) receiving daily L-asparaginase as a single agent when in complete remission. Changes in the prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, while statistically significant, remained within or close to the normal range during the study. Platelet function also remained normal during the study. In contrast, levels of protein C antigen decreased to a mean of 42%, a significant change from pretreatment values. Levels of antithrombin III (AT III) were likewise depressed to 15 mg/dL (34% of pretreatment value). Despite these changes in the levels of physiologic inhibitors of coagulation, this schedule of L-asparaginase administration was associated with only rare clinical thrombosis, and this study suggests that the development of this complication may be dependent on the presence of additional factors.

Hypermobility and Knee Injuries.

In brief: The effect of knee joint hypermobility on knee injury is not fully clear. Inherited flexibility probably plays little role in the causes of most knee injuries. The exception is patellar dislocation, which is strongly associated with hypermobility. Discussions of hypermobility often reflect confusion over the difference between flexibility and laxity. In general, flexibility refers to a joint's range of motion and is a function of muscle and tendon tightness, while laxity refers to joint distraction and shear and is a function of ligament tightness. Research on hypermobility has focused on flexibility; the relationship between injury and joint laxity (ligament stability) has not been studied prospectively. Such research could yield information useful for injury prevention.

The effect of exercise on anterior-posterior knee laxity.

A commercial knee laxity testing device was used to quantitate anterior and posterior laxity before and after exercise. Measurements were made at 20 degrees of knee flexion and with a displacement force of 133 N (30 pounds). In sedentary controls no significant change in laxity was noted over 2 hours. Squat power lifters sustained no significant change in laxity after a series of squats (0.4 to 0.7 cm) using 1.6 times body weight. However, 18% to 20% increases in mean anterior and posterior laxity were noted in college basketball players after 90 minutes of practice and in recreational runners after a 10 km race. The role of muscle relaxation in such tests was also evaluated by measuring laxity in normal knees before and during general anesthesia. Negligible laxity change was noted. Thus, functionally "complete" muscle relaxation can be obtained during testing in the cooperative individual. In conclusion, basketball players and distance runners experienced a transient increase in anterior and posterior laxity during exercise. Power lifters doing squats did not demonstrate a significant change in laxity. It appears that repetitive physiologic stresses at a high strain rate produce significant ligamentous laxity, while a relatively few large stresses at a low strain rate do not.

Treatment of symptomatic spondylolysis and spondylolisthesis with the modified Boston brace.

Sixty-seven persons with symptomatic spondylolysis or grade 1 spondylolisthesis were treated with the modified Boston brace. The average age was 16.0 years, and the average follow-up was 2.5 years. Following treatment, 52 persons (78%) had either an excellent or good result with no pain and returned to full activities. Nine (13%) continued to have mild symptoms, and six (9%) subsequently required fusion in situ. Twelve of the patients showed radiographic evidence of healing of their pars defect(s). This group and those with the best overall results tended to be men with spondylolysis and relatively acute onset of symptoms. Age, delay in treatment, spina bifida, and bone scan result did not correlate with the ultimate clinical result.

The effect of mitotic inhibitors on DNA strand size and radiation-associated break repair in Down syndrome fibroblasts.

The effect of mitotic inhibitors on formation and repair of DNA breaks was studied in cultured fibroblasts from patients with Down syndrome in order to investigate the hypothesis that the karyotyping procedure itself may play a role in the increased chromosome breakage seen in these cells after gamma radiation exposure. Using the nondenaturing elution and alkaline elution techniques to examine fibroblasts from Down syndrome patients and from controls, no specific abnormalities in Down syndrome cells could be detected after exposure to mitotic inhibitors, including rate and extent of elution of DNA from filters as well as repair of radiation-induced DNA breaks. In both normal and Down syndrome cell strains, however, exposure to mitotic inhibitors was associated with a decrease in cellular DNA strand size, suggesting the presence of drug-induced DNA strand breaks. The mechanism of increased chromosome sensitivity of Down syndrome cells to gamma radiation remains unknown.