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Angiotensin II (ANG II) and its receptors, AT1 and AT2, may modulate kidney development. To define the temporal and spatial distribution of AT1 and AT2 receptors and their mRNAs during nephrogenesis, fetal, newborn, and adult rat kidneys were studied using reverse transcription-polymerase chain reaction and radioligand binding autoradiography. AT1 expression was minimal at embryonic day 14 (E14), highly expressed at E20, and persisted into adulthood. Conversely, AT2 expression was easily detected from E14 through postnatal day 7 but was undetectable by postnatal day 28. At E14, 76% of the receptors were AT2, 24% were AT1, and both were found in the undifferentiated mesenchyme. By E17, AT1 comprised 40% of the receptors and localized to mature nephron segments, whereas AT2 remained within both condensed mesenchyme and differentiating epithelia. The dissociation constants for AT1 and AT2 were 0.45 +/- 0.09 nM and 0.73 +/- 0.15 nM, respectively, at E17, similar to adult values. By E20, AT1 and AT2 colocalized to the outer medullary stripe, deep nephrons, medullary rays, and blood vessels, while AT2 continued to predominate in the actively differentiating cortex. The presence of both subtypes of receptors capable of binding ANG II during early nephrogenesis and the time-dependent and structure-specific regulation of receptor localization confirm a regulated developmental program for receptor expression and suggest important roles for AT1 and AT2 in renal morphogenesis.

Infection of biomaterial implants is an expensive and devastating complication of orthopaedic surgery historically ranging from less than 1% in primary total knee arthroplasty (TKA) to 10% in revision TKA. An in vivo animal model was developed to test the efficacy of innovative therapies for the prevention of biomaterial centered infections caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). Twenty-two New Zealand White rabbits were used in this study. After proper anesthesia, a stainless-steel screw with a high molecular weight polyethylene (UHMWPE) washer was cemented in a defect created in the intra-articular, nonarticulating portion of the lateral femoral condyle of each knee. After closure of the joint capsule, each knee was inoculated with 0, lo2, lo', or lo4 colony forming units (CFU) of MRSA. Animals were sacrificed after 7 days at which time joint aspirate, tissues and biomaterial samples were examined for evidence of infection.A total of 42 knees were used for analysis. When saline was injected into the knee, 0/10 of the knees demonstrated evidence of biomaterial centered infection (with the contralateral knee receiving lo4 CFU MRSA). Four of 10 knees developed a biomaterial centered infection when lo2 CFU MRSA was introduced. Seven out of 10 knees developed a biomaterial centered infection when either lo3 or lo4 CFU MRSA was injected. No evidence of septicemia (positive blood cultures) was found in any animal. This rabbit knee model utilizes commonly employed inexpensive orthopaedic implant materials in an in vivo milieu and provides an effective method for the evaluation of treatments for biomaterial centered infections.

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In this study, proximal segment stability was improved with a greater quantity of screws and with locked interlocking screws.

Bisphosphonates are the most widely used medication to treat osteoporosis. Recent reports have documented an association between chronic bisphosphonate use and femoral insufficiency fractures. This article describes an 84-year-old woman with a diagnosis of osteoporosis treated with bisphosphonate medications for 9 years. She presented with left groin pain, and magnetic resonance imaging revealed a subtrochanteric femoral stress fracture. Operative and nonoperative management was discussed with the patient, and she chose to undergo prophylactic intramedullary nailing of the left femur. Six months postoperatively, she was asymptomatic and ambulating without assistive devices.This article describes successful management of a bisphosphonate-related femoral insufficiency fracture. The presence of groin or thigh pain in a patient taking bisphosphonates should alert the physician to the possibility of insufficiency fracture of the proximal femur, and plain radiographs should be obtained. If these radiographs show lateral cortical thickening, consideration should be given to prophylactic intramedullary femoral nailing. The risks and benefits of prophylactic fixation vs conservative management should be discussed with the patient. A recent series showed a high failure rate with conservative treatment of these fractures. A dialogue with the primary care physician should be initiated to determine the necessity of bisphosphonate therapy, and, if deemed necessary, an alternative class of medications should be considered.

The purpose of this study was to elaborate on the association between the use of bisphosphonates and low-energy femoral shaft fractures. A retrospective review was performed between January 2000 and January 2010 to identify patients older than 65 years who sustained femoral shaft diaphyseal fractures (Orthopaedic Trauma Association classification 32 A [extra-articular], B [partial articular/unicondylar], or C [complete articular/bicondylar]) using ICD-9 code 821.01. After exclusion criteria were applied, 77 patients remained for analysis. A total of 66 patients had no history of bisphosphonate therapy, and 11 patients had received bisphosphonate therapy for >2 years prior to admission. All 11 patients in the bisphosphonate group had sustained a low-energy fall from a standing height or lower. In 9 of 11 (82%) patients in the bisphosphonate group, radiographs resembled transverse shaft fractures with lateral cortical beaking that have been observed in patients on chronic bisphosphonate therapy.Our series echoes the findings of other authors, who found that bisphosphonate use is associated with lateral cortical beaking and low-energy, transverse fractures of the femoral shaft. Further research is needed to determine if specific medications and length of treatment are important risk factors.

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