Erratum to: High Interspecimen Variability in Engagement of the Anterolateral Ligament: An In Vitro Cadaveric Study

Clinical Orthopaedics and Related Research® -     

Renal disease in patients with HIV infection: epidemiology, pathogenesis and management

With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast.Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.     

Primary and secondary hyperoxaluria: Understanding the enigma

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.     

Heat shock protein 70 kDa chaperone/DnaJ cochaperone complex employs an unusual dynamic interface

The heat shock protein 70 kDa (Hsp70)/DnaJ/nucleotide exchange factor system assists in intracellular protein (re)folding. Using solution NMR, we obtained a three-dimensional structure for a 75-kDa Hsp70–DnaJ complex in the ADP state, loaded with substrate peptide. We establish that the J domain (residues 1–70) binds with its positively charged helix II to a negatively charged loop in the Hsp70 nucleotide-binding domain. The complex shows an unusual “tethered” binding mode which is stoichiometric and saturable, but which has a dynamic interface. The complex represents part of a triple complex of Hsp70 and DnaJ both bound to substrate protein. Mutagenesis data indicate that the interface is also of relevance for the interaction of Hsp70 and DnaJ in the ATP state. The solution complex is completely different from a crystal structure of a disulfide-linked complex of homologous proteins [Jiang, et al. (2007) Mol Cell 28:422–433].     

Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

Fibrosis is a fundamental component of the adverse structural remodeling of myocardium present in the failing heart. Replacement fibrosis appears at sites of previous cardiomyocyte necrosis to preserve the structural integrity of the myocardium, but not without adverse functional consequences. The extensive nature of this microscopic scarring suggests cardiomyocyte necrosis is widespread and the loss of these contractile elements, combined with fibrous tissue deposition in the form of a stiff in-series and in-parallel elastic elements, contributes to the progressive failure of this normally efficient muscular pump. Cellular and molecular studies into the signal-transducer-effector pathway involved in cardiomyocyte necrosis have identified the crucial pathogenic role of intracellular Ca²⁺ overloading and subsequent induction of oxidative stress, predominantly confined within its mitochondria, to be followed by the opening of the mitochondrial permeability transition pore that leads to the destruction of these organelles and cells. It is now further recognized that Ca²⁺ overloading of cardiac myocytes and mitochondria serves as a prooxidant and which is counterbalanced by an intrinsically coupled Zn²⁺ entry serving as antioxidant. The prospect of raising antioxidant defenses by increasing intracellular Zn²⁺ with adjuvant nutriceuticals can, therefore, be preferentially exploited to uncouple this intrinsically coupled Ca²⁺–Zn²⁺ dyshomeostasis. Hence, novel yet simple cardioprotective strategies may be at hand that deserve to be further explored.     

Difference between selected and obtained shade for metal-ceramic crown systems

PURPOSE: This study evaluated shade differences between selected shades (2 M 2, 3D Master system, Vitazahnfabrik) and obtained shades of crowns made with a gold electroforming metal-ceramic system (Gramm Technik GmbH) veneered with porcelain and compared those crowns with crowns made with In-Ceram alumina blocks (Vitazahnfabrik) in a CEREC 3D machine (Sirona Dental Systems LLC) and with a porcelain-fused-to-metal system (Classic IV gold alloy, Jensen Dental). MATERIALS AND METHODS: Ten crown restorations were constructed for each group (gold electroforming, In-Ceram alumina and porcelain-fused-to-metal) following the manufacturers' directions. Shade difference between a selected shade (2 M 2) and the obtained shades was measured using an intraoral spectrophotometer (Easyshade). Data was statistically analyzed. RESULTS: Shade differences for the three groups were between 1.21-1.56, with the gold electroformed crowns having the lowest mean and the porcelain-fused-to-metal having the highest mean. Statistical analysis with ANOVA revealed a significant difference among the three systems (p < .0001). Further statistical analysis with post hoc Tukey's test revealed a significant difference in means between the porcelain-fused-to-metal group and the other two groups (p < 0.021). No significant difference was detected between the means of the gold electroformed crowns and the In-Ceram alumina crowns (p = 0.981). CONCLUSION: Veneered gold electroformed crowns and In-Ceram crowns produced shade matching significantly better than that obtained with porcelain-fused-to-metal crowns.