Atypical Femur Fractures: A Review

Bisphosphonates are one of the most commonly prescribed medications for the treatment of osteoporosis. Their use has greatly decreased the number of osteoporosis-related vertebral and nonvertebral fractures. Recently, however, a relationship between long-term bisphosphonate use and subtrochanteric and femoral shaft fractures has been elucidated. These low-energy fractures, termed atypical femur fractures, exhibit unique characteristics in their pathophysiology, presentation, and radiographic appearance compared with more traditional high-energy femur fractures. Here we provide a review based on the most recent literature of the pathophysiology, presentation, evaluation, and management of these fractures. Despite an abundance of literature, atypical femur fractures remain difficult to treat, and surgeons must be aware of the tricks and complications associated with their management.     

Micropatterning of costimulatory ligands enhances CD4+ T cell function

Spatial organization of signaling complexes is a defining characteristic of the immunological synapse (IS), but its impact on cell communication is unclear. In T cell–APC pairs, more IL-2 is produced when CD28 clusters are segregated from central supramolecular activation cluster (cSMAC)-localized CD3 and into the IS periphery. However, it is not clear in these cellular experiments whether the increased IL-2 is driven by the pattern itself or by upstream events that precipitate the patterns. In this article, we recapitulate key features of physiological synapses using planar costimulation arrays containing antibodies against CD3 and CD28, surrounded by ICAM-1, created by combining multiple rounds of microcontact printing on a single surface. Naïve T cells traverse these arrays, stopping at features of anti-CD3 antibodies and forming a stable synapse. We directly demonstrate that presenting anti-CD28 in the cell periphery, surrounding an anti-CD3 feature, enhances IL-2 secretion by naïve CD4⁺ T cells compared with having these signals combined in the center of the IS. This increased cytokine production correlates with NF-κB translocation and requires PKB/Akt signaling. The ability to arbitrarily and independently control the locations of anti-CD3 and anti-CD28 offered the opportunity to examine patterns not precisely attainable in cell–cell interfaces. With these patterns, we show that the peripheral presentation of CD28 has a larger impact on IL-2 secretion than CD3 colocalization/segregation.     

Streptococcus bovis catheter infection and the short bowel syndrome

Streptococcus bovis bacteremia has been associated with several gastrointestinal disorders, most notably carcinoma of the colon. This report describes a 57-year-old woman with short bowel syndrome in whom S. bovis bacteremia and an infection of an indwelling parenteral nutrition catheter developed. A barium enema revealed diverticula and a foreshortened small intestine. This case implicates the short bowel syndrome in the pathogenesis of S. bovis bacteremia and supports empiric antibiotic coverage for both skin flora and enteric pathogens in patients with Hickman catheter sepsis and known gastrointestinal pathologic conditions.     

Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer.

The prognosis for patients with the high-grade cerebral glioma glioblastoma multiforme is poor. The median survival for primary tumors is < 12 months, with most recurring at the site of the original tumor, indicating that a more aggressive local therapy is required to eradicate the unresectable "nests" of tumor cells invading into adjacent brain. Two adjuvant therapies with the potential to destroy these cells are porphyrin-sensitized photodynamic therapy (PDT) and boron-sensitized boron neutron capture therapy (BNCT). The ability of a boronated porphyrin, 2,4-(alpha, beta-dihydroxyethyl) deuteroporphyrin IX tetrakiscarborane carboxylate ester (BOPP), to act as a photosensitizing agent was investigated in vitro with the C6 rat glioma cell line and in vivo with C6 cells grown as an intracerebral tumor after implantation into Wistar rats. These studies determined the doses of BOPP and light required to achieve maximal cell kill in vitro and selective tumor kill in vivo. The data show that BOPP is more dose effective in vivo by a factor of 10 than the current clinically used photosensitizer hematoporphyrin derivative and suggest that BOPP may have potential as a dual PDT/BNCT sensitizer.     

Powdered infant formula as a source of Salmonella infection in infants.

Powdered infant formula is not sterile and may be intrinsically contaminated with pathogens, such as Salmonella enterica, that can cause serious illness in infants. In recent years, at least 6 outbreaks of Salmonella infection in infants that have been linked to the consumption of powdered infant formula have been reported. Many of these outbreaks were identified because the Salmonella strains were unique in some way (e.g., a rare serotype) and a well-established Salmonella surveillance network, supported by laboratories capable of serotyping isolates, was in place. Another common feature of the outbreaks was the low level of salmonellae detected in the implicated formula (salmonellae may be missed in routine testing). These outbreaks likely represent only a small proportion of the actual number of Salmonella infections in infants that have been linked to powdered infant formula. Managing this problem requires a multidimensional approach in which manufacturers, regulators, and caregivers to infants can all play a role.     

Utility of pulse oximetry in diagnosing pneumonia in nursing home residents

BACKGROUND: The differential diagnosis of acute infection in elderly nursing home patients is often difficult. This study evaluated pulse oximetry in pneumonia in this population. METHODS: A case-control study was performed in a veteran's nursing home involving 2 analyses: (1) pneumonia patients (case subjects) were compared with patients with nonpulmonary infections (control subjects) at time of acute infection; (2) differences in paired values measured at time of infection versus a noninfected baseline were compared for pneumonia patients and control subjects. Vital signs including pulse oximetry were obtained routinely (at least monthly) and with acute illness. RESULTS: Oxygen saturations were lower in 45 pneumonia patients than in 22 patients with acute nonpulmonary infections (P < 0.001). An oxygen saturation < 94 gave a sensitivity for pneumonia of 80%, specificity of 91%, and positive predictive value of 95%. The drop in oxygen saturation from the last baseline value was greater in pneumonia patients than in control subjects (P < 0.001). The sensitivity of an oxygen saturation drop >3% from baseline for pneumonia was 73% with specificity and positive predictive values of 100%. CONCLUSIONS: Pulse oximetry may be very helpful in evaluating acutely infected nursing home residents. The present study suggests that in acutely infected nursing home patients, a decrease in oxygen saturation of >3% from baseline, as well as a single oxygen saturation of <94, should suggest pneumonia. A decrease from baseline of <4% or a single oxygen saturation of 94 or higher suggests that pneumonia is unlikely.     

Human burst-forming units-erythroid need direct interaction with stem cell factor for further development

To understand the factors that regulate the early growth and development of immature erythroid progenitor cells, the burst-forming units-erythroid (BFU-E), it is necessary to have both highly purified target cells and a medium free of serum. When highly purified human blood BFU-E were cultured in a serum-free medium adequate for the growth of later erythroid progenitors, BFU-E would not grow even with the addition of recombinant human interleukin-3 (rIL-3), known to be essential for these cells. However, the addition of recombinant human stem cell factor (rSCF), which supports germ cell and pluripotential stem cell growth, stimulated BFU-E to grow equally well in serum-free as in serum-containing medium. Limiting dilution studies showed that rSCF acts directly on the BFU-E that do not require accessory cells for growth. Furthermore, rSCF was necessary for BFU-E development during the initial 7 days of culture, until these cells reached the stage of the late progenitors, the colony-forming units-erythroid (CFU-E). These studies indicate that early erythropoiesis is dependent on the direct action of SCF that not only affects early stem cells but is continually necessary for the further development of committed erythroid progenitor cells until the CFU-E stage of maturation.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.