Citations

ABSTRACT Staphylococcus lugdunensis is a coagulase-negative staphylococcus that has several similarities to Staphylococcus aureus . S. lugdunensis is increasingly being recognized as a cause of prosthetic joint infection (PJI). The goal of the present retrospective cohort study was to determine the laboratory and clinical characteristics of S. lugdunensis PJIs seen at the Mayo Clinic in Rochester, MN, between 1 January 1998 and 31 December 2007. Kaplan-Meier survival methods and Wilcoxon sum-rank analysis were used to determine the cumulative incidence of treatment success and assess subset comparisons. There were 28 episodes of S . lugdunensis PJIs in 22 patients; half of those patients were females. Twenty-five episodes (89%) involved the prosthetic knee, while 3 (11%) involved the hip. Nine patients (32%) had an underlying urogenital abnormality. Among the 28 isolates in this study tested by agar dilution, 24 of 28 (86%) were oxacillin susceptible. Twenty of the 21 tested isolates (95%) lacked mecA , and 6 (27%) of the 22 isolates tested produced β-lactamase. The median durations of parenteral β-lactam therapy and vancomycin therapy were 38 days (range, 23 to 42 days) and 39 days (range, 12 to 60 days), respectively. The cumulative incidences of freedom from treatment failure (standard deviations) at 2 years were 92% (±7%) and 76% (±12%) for episodes treated with a parenteral β-lactam and vancomycin, respectively ( P = 0.015). S. lugdunensis is increasingly being recognized as a cause of PJIs. The majority of the isolates lacked mecA . Episodes treated with a parenteral β-lactam antibiotic appear to have a more favorable outcome than those treated with parenteral vancomycin.

Local release of TGF-β during times of high bone turnover leads to elevated levels within the bone microenvironment, and we have shown that TGF-β suppresses osteoclast apoptosis. Therefore, understanding the influences of TGF-β on bone resorbing osteoclasts is critical to the design of therapies to reduce excess bone loss. Here we investigated the mechanisms by which TGF-β sustains suppression of osteoclast apoptosis. We found TGF-β rapidly increased leukemia inhibitory factor (LIF) expression and secretion by phosphorylated mothers against decapentaplegic-dependent and -independent signaling pathways. TGF-β also induced suppressor of cytokine signaling 3 (SOCS3) expression, which was required for TGF-β or LIF to promote osteoclast survival by. Blocking LIF or SOCS3 blocked TGF-β promotion of osteoclast survival, confirming that LIF and SOCS3 expression are necessary for TGF-β-mediated suppression of osteoclast apoptosis. Investigation of the mechanisms by which LIF promotes osteoclast survival revealed that LIF-induced expression of Bcl-XL and repressed Bcl-2 interacting domain expression by activating MAPK kinase, AKT, and nuclear factor-κB pathways. Suppression of Janus kinase/signal transducer and activator of transcription signaling further increased Bcl-XL expression and enhanced osteoclast survival, supporting that this pathway is not involved in prosurvival effects of TGF-β and LIF. These data show that TGF-β coordinately induces LIF and SOCS3 to promote prosurvival signaling. This alters the ratio of prosurvival Bcl2 family member Bcl-XL to proapoptotic family member Bcl-2 interacting domain, leading to prolonged osteoclast survival.

Patient safety is a complex issue that is constantly evolving. Communication via standardized drug ordering is recognized as one of the key elements for providing a safer hospital stay, as well as a stronger patient outcome. This feature provides examples of standardized drug prescribing and a forum for discussion. If you have a template that you believe may be beneficial to other hospital pharmacies, please submit it along with answers to the questions (as shown in the text of this article) to Joyce Generali, Director of Drug Information, Kansas University Medical Center, 3901 Rainbow Boulevard, Mail Stop 4040, Kansas City, KS 66160 or e-mail jgeneral@kumc.edu .

Cultivation of primary hepatocytes as spheroids creates an efficient three-dimensional model system for hepatic studies in vitro and as a cell source for a spheroid reservoir bioartificial liver. The mechanism of spheroid formation is poorly understood, as is an explanation for why normal, anchorage-dependent hepatocytes remain viable and do not undergo detachment-induced apoptosis, known as anoikis, when placed in suspension spheroid culture. The purpose of this study was to investigate the role of E-cadherin, a calcium-dependent cell adhesion molecule, in the formation and maintenance of hepatocyte spheroids. Hepatocyte spheroids were formed by a novel rocker technique and cultured in suspension for up to 24 h. The dependence of spheroid formation on E-cadherin and calcium was established using an E-cadherin blocking antibody and a calcium chelator. We found that inhibiting E-cadherin prevented cell–cell attachment and spheroid formation, and, surprisingly, E-cadherin inhibition led to hepatocyte death through a caspase-independent mechanism. In conclusion, E-cadherin is required for hepatocyte spheroid formation and may be responsible for protecting hepatocytes from a novel form of caspase-independent cell death.

Abstract ABSTRACT: The cellular mechanisms for bone loss in type I (postmenopausal) osteoporosis are highly controversial. We attempted to resolve this by assessing rates of formation and resorption of iliac cancellous bone by a new histomorphometric method in 89 women with osteoporosis (mean age + SD, 66 + 6 years) and in 32 carefully selected normal postmenopausal women (64 + 6 years). In the osteoporotic women, bone resorption rate was increased by 39% (P <0.05) at the cellular level and by 67% (P <0.05) at the tissue level, whereas bone formation was unchanged at the tissue level but decreased by 14% (P <0.01) at the cellular (osteoblast) level. This pronounced remodeling imbalance (P <0.001) was probably exacerbated by a 45% increase (P < 0.1) in activation frequency of new remodeling foci. These abnormalities were associated with a high rate of cancellous bone loss (median, 5.8%/year versus 0.1%/year in controls). Thus, accelerated loss of cancellous bone in type I osteoporosis results from the combination of increased bone resorption and inadequate compensation by bone formation.

Abstract Lack of adequate data concerning the effect of age on biochemical variables relating to bone and mineral metabolism hampers research on age-related bone loss in women. Furthermore, to detect disease and to monitor therapy, clinical laboratories require reference values derived from an appropriate population sample. Therefore, we determined the age-specific distribution of values for serum concentrations of calcium, inorganic phosphorus, alkaline phosphatase, bone Gla protein, and parathyroid hormone; for creatinine clearance; for fasting urinary calcium:creatinine ratio; and for 24 h urinary excretion of calcium, hydroxyproline, and cyclic AMP in a population-based sample of 301 white women. From this sample, a healthy subgroup of 181 women was identified by medical record review. Age-related effects were seen in all variables except serum calcium and phosphorus. Moreover, substantial differences between the population sample and the healthy subgroup were noted in values for creatinine clearance, serum alkaline phosphatase, and 24 h urinary calcium excretion. These observations may prove useful for assessment of normality in other populations of aging white women.

Abstract We have compared two assays for osteocalcin (BGP, bone gla protein), one based on a monoclonal antibody, the other based on a polyclonal serum, in an effort to better understand the factors that contribute to the wide variation reported for osteocalcin normal ranges. The two assays compared well using serum samples, with a correlation coefficient of 0.9071 (n = 48). However, the monoclonal antibody assay returns values increased over the polyclonal assay by approximately 1.5-fold. Gel permeation studies indicate that these larger values are due primarily to increased reactivity in the monoclonal assay with high- and low-molecular-weight forms of osteocalcin in plasma; both assays give similar reactions to intact osteocalcin. Analysis of samples from individuals with increased bone resorption due to parathyroid hormone administration reveals that the decrease seen in osteocalcin values after hormone infusion occurs primarily in the fraction that corresponds to intact osteocalcin. During the course of these studies, we re-evaluated the extinction coefficient for osteocalcin, arriving at the value E = 1.33 mg/ml−1, cm−1. We also observed a significant negative interference in both assays (and a commercial assay) caused by hemolysis. This interference is due to proteolysis of osteocalcin by enzymatic activity released from the lysed red cells.