The Knee Society Index of Severity for failed total knee arthroplasty: practical application.

Previous classifications of severity for total knee arthroplasty revisions have been based largely on bone loss of the femur and tibia. These approaches failed to address the more technically difficult issues in revision surgery such as surgical exposure, contractures, extremity alignment, implant removal, soft tissue stability (in the anteroposterior and in the sagittal planes), extensor mechanism integrity, and patellar revisability. Through the Knee Society, the authors developed a severity index that incorporated these latter factors into one measure. The current authors describe the application of the Knee Society Index of Severity for failed total knee arthroplasty and its method of scoring.     

Tip-apex distance of intramedullary devices as a predictor of cut-out failure in the treatment of peritrochanteric elderly hip fractures

A tip-apex distance (TAD) of greater than 25 mm has been shown to be an accurate predictor of lag screw cut-out when sliding hip screws (SHS) are used to treat peritrochanteric (PT) hip fractures. The purpose of this study was to determine which factors, including TAD, correlated with successful clinical outcomes of PT hip fractures surgically treated with intramedullary (IM) devices. A total of 192 patients were included in this retrospective study. The TAD values of this cohort were radiographically analysed at a mean follow-up of 13 months. This was correlated with limited functional status and the rate of revision for implant failure or inability to achieve fracture union. Only 82 patients had adequate follow-up to fracture union or definitive failure. There were 46 intertrochanteric (IT) hip fractures and 36 subtrochanteric (ST) fractures. Overall, seven patients (8.5%) went on to experience lag screw cut-out. The average TAD of the patients who did not cut-out was 18 mm, compared to 38 mm for those who did (p = 0.012). All patients who cut-out had IT fractures (p = 0.017). The percentage of cut-outs correlated directly to both the severity of IT fractures and the TAD. Using a cutoff of 25 mm there was a statistically significant difference in the incidence of lag screw cut-out (p < 0.001). As in sliding hip screws, surgeons should strive for a TAD less than 25 mm when using IM devices in the treatment of PT hip fractures to help avoid lag screw cut-out.     

Characteristics of elderly patients admitted to an urban tertiary care hospital with osteoporotic fractures: correlations with risk factors, fracture type, gender and ethnicity

Osteoporosis is a major public health problem in the United States of America and around the world, largely due to the morbidity and mortality associated with osteoporotic fractures. In the past decade, large epidemiologic studies have contributed greatly to our understanding of patients who fracture. However, most studies are limited to postmenopausal white women. In this retrospective review, we analyze data from 185 men and women with acute fragility fractures who received osteoporosis consultations during admission to a single urban hospital between 2001 and 2003. Men and women differed in terms of risk factors for falls and osteoporosis but had areal bone mineral density (BMD) measurements remarkably similar, except at the total hip. Black and Hispanic subjects with fractures were significantly younger than whites yet were much more likely to have serious co-morbidities, such as diabetes mellitus and hypertension. In spite of significantly higher BMD measurements, black patients had the highest rates of vitamin D deficiency and secondary hyperparathyroidism. Patients admitted with hip fractures differed from those with non-hip fractures on a number of important variables. Based on these data, we conclude that elderly subjects admitted to an urban hospital with osteoporotic fractures are a heterogeneous group, with features that vary according to fracture type, gender and ethnicity. Future studies of patients with clinical fragility fractures should include ample numbers of men and ethnic minorities, since differences in underlying risk factors may suggest alternative strategies for fracture prevention.     

Stimulation of pyruvate dehydrogenase activity in intact rat adipocytes by insulin mediator from rat skeletal muscle

This study compared the effects of insulin and insulin mediator from skeletal muscle of control and insulin-treated rats on intact adipocyte pyruvate dehydrogenase. Increasing insulin concentrations stimulated pyruvate dehydrogenase activity in a biphasic manner with a maximal stimulation at 100 microU/ml which was 2-fold and sustained for up to 1 h. The mediators from control or insulin-treated rats also stimulated pyruvate dehydrogenase of intact adipocytes with the effect increasing in a linear manner up to a 1:10 final dilution. The latter mediator had twice the stimulatory activity as the former. Peak stimulation of pyruvate dehydrogenase by the mediators was attained within 10 min of incubation. The enzyme activity rapidly declined thereafter, with the stimulation by mediator from control rats decreasing at a faster rate than that due to mediator from insulin-treated rats. The stimulatory effect of the mediators on adipocyte pyruvate dehydrogenase was found to be additive to that of insulin. This study demonstrates: 1) that insulin mediator can act on mitochondrial pyruvate dehydrogenase of intact, functional adipocytes as it does on isolated intact or broken mitochondria; 2) that the mediator is degraded by the adipocyte; and 3) that the amount of mediator generated by insulin probably limits the stimulation of pyruvate dehydrogenase by insulin. These findings further substantiate the physiological relevance of this putative insulin second messenger.     

MR of focal liver lesions: Comparison of breath-hold and non-breath-hold hybrid rare and conventional spin-echo T2-weighted pulse sequences

To compare liver lesion detection rates, tissue signal and noise data, and qualitative parameters for breathhold (BH) and non-breath-hold (NBH) hybrid rapid acquisition with relaxation enhancement (RARE) and conventional spin-echo (CSE) T2-weighted (CSE-T2) MR sequences, 20 patients were imaged using all three sequences. Lesion detection rates were 73.5% for the CSE-T2 sequence and 81.1% and 88.6% for the BH-RARE and NBH-RARE sequences, respectively (P = .027). Mean lesion-to-liver signal-difference-to-noise ratio for the NBH-RARE sequence was 14.0 ± 11.5, significantly greater than 9.8 ± 7.8 obtained for the BH-RARE sequence (P = .050) and 9.0 ± 6.2 obtained for the CSE-T2 sequence (P = .015). The NBH-RARE sequence demonstrated fewer artifacts and greater overall image quality compared to the CSE-T2 sequence. The NBH-RARE sequence is a useful alternative to the CSE-T2 sequence providing a higher mean lesion-to-liver signal-difference-to-noise ratio and lesion detection rate and better overall image quality.     

The effects of insulin-like growth factor analogues on survival of cultured cerebral cortex and cerebellar granule neurones

Insulin and insulin-like growth factors (IGF-I, IGF-II) are closely related polypeptides which are found in the CNS and which promote neuronal survival and neurite outgrowth. They are each associated with specific cell surface receptors and several soluble binding proteins (IGFBPs) which are involved in regulating function and availability. Two analogues of IGF-I were produced by site directed mutagenesis: [Gln3, Ala4, Tyr15, Leu16]IGF-1 (QAYL-IGF) and a B-chain mutant in which the first 16 amino acids of IGF-1 were replaced by the first 17 amino acids of insulin. These analogues have significantly reduced binding affinity for IGFBPs. Using glucose deprivation as a damaging stimulus and assaying lactate dehydrogenase released from cultures as a marker for cell death, we have investigated the effect of IGF analogues on cell death of cerebrocortical and cerebellar granule cell cultures. In the presence of IGF-I, QAYL-IGF or B-chain mutant, the amount of LDH released from cortical and cerebellar granule cell cultures was significantly reduced compared to control (no glucose), indicating that these molecules promote survival. Both QAYL and B-chain mutants, which have reduced affinity for IGFBPs, are as effective as IGF-I in promoting cell survival in conditions of glucose deprivation and their reduced affinity for IGFBPs has no apparent deleterious effect on their neuroprotective function. We also show that the neuroprotective effect of the IGF analogues is due to a direct effect on the neurones in these cultures and is independent of the presence of glia.     

Reactivation of polyomavirus in bone marrow transplant recipients.

Polyomavirus was detected in the urine samples of 12 (48%) out of 25 patients within three months of receiving a bone marrow transplantation. The virus was first detected 11 to 46 days after the transplantation and excretion persisted for up to 42 days. Detection of the virus was not associated with symptoms and it seemed to be a marker of immunosuppression.     

Lateral unicompartmental knee arthroplasty: A review

Isolated lateral compartment osteoarthritis of the knee is a rare condition affecting approximately 1% of the population, which is ten times less common than osteoarthritis affecting only the medial compartment. Unicompartmental knee arthroplasty(UKA) has many potential advantages over total knee arthroplasty. The benefits of UKA include a smaller incision, preservation of more native tissue(including cruciate ligaments and bone), decreased blood loss, and better overall proprioception. When UKA was first introduced in the 1970 s, the outcomes of medial UKA(MUKA) were poor, but the few cases of lateral UKA(LUKA) showed promise. Since that time, there has been a relative paucity of literature focused specifically on LUKA given it is a rare procedure. Refinements in patient selection criteria, implant design, and surgical technique have been made leading to increased popularity. A review of the recent literature reveals that LUKA is associated with excellent long-term clinical outcomes and implant survivorship when performed in properly selected patients. Implant design options include fixed vs mobile bearing as well as metal backed vs all polyethylene tibial component, with improved outcomes noted with fixed bearing designs. Three reasons cited for revision(i.e., fracture of the femoral component, fracture of the tibial component, and valgus malalignment) had been reported in past literature but not recently. Presently, while rare, the most common cause of failure and need for revision are osteoarthritis progression and aseptic loosening. Despite the need for an occasional revision procedure, the survivorship of LUKA is comparable to MUKA, although it should be noted that outcomes of MUKA have been notably varied. Continued pursuit of improved techniques and implant designs will continue to show LUKA to be an excellent procedure for appropriately indicatedpatients.     

Apoptosis of medulloblastoma cells in vitro follows inhibition of farnesylation using manumycin A.

Medulloblastoma is a malignant cerebellar tumor usually manifesting in childhood. We have previously shown that blocking the mevalonate pathway with lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibits medulloblastoma proliferation and induces apoptosis in vitro. The underlying mechanism may involve blocking post-translational modification of important mitogenic signal-transduction proteins. We show that p21 ras processing is blocked by lovastatin, suggesting that inhibition of isoprenylation may be important in lovastatin-induced apoptosis. To test this hypothesis, manumycin A, an antibiotic which inhibits farnesyl protein transferase and thus farnesylation, was administered to 4 medulloblastoma cell lines in vitro. We found that blocking protein farnesylation with manumycin A was followed by apoptosis in a time- and dose-dependent manner. However, cell death induced by manumycin A was uniformly more rapid and efficient, requiring only 12 to 24 hr of treatment, than lovastatin-induced apoptosis, which required 36 to 96 hr (depending on the cell line tested). In addition, unlike lovastatin, which caused cell-cycle arrest in G1 phase and HMG-CoA reductase gene up-regulation, manumycin A had no effect on the cell cycle and resulted in down-regulation of HMG-CoA reductase gene expression. In both lovastatin- and manumycin A-treated cells, cellular cysteine protease precursor (CPP32) was activated, confirming the occurrence of apoptosis.