Hypoxia and HIF-1α expression in the epiphyseal cartilage following ischemic injury to the immature femoral head

HIF-1α has been shown to be a central mediator of cellular response to hypoxia. The role it plays after ischemic injury to the immature femoral head is unknown. The purpose of this study was to determine the region of the femoral head affected by hypoxia following ischemic injury to the immature femoral head and to determine the site of HIF-1α activation and revascularization. We hypothesize that the epiphyseal cartilage, rather than the bony epiphysis, is the site of HIF-1α activation following ischemic osteonecrosis and that the epiphyseal cartilage plays an important role in the revascularization process.Materials and methodsFemoral head osteonecrosis was surgically induced in 56 immature pigs. Hypoxyprobe staining, cell viability assay, HIF-1α western blot, RT-qPCR of HIF-1α, VEGF, VEGFR2, and PECAM, and micro-CT assessments of microfil-infused femoral heads were performed.ResultsSevere hypoxia was present in the bony epiphysis and the lower part of the epiphyseal cartilage following ischemia. In the bony epiphysis, extensive cell death and tissue necrosis was observed with degradation of proteins and RNAs which precluded further analysis. In the epiphyseal cartilage, the loss of cell viability was limited to its deep layer with the remainder of the cartilage remaining viable. Furthermore, the cartilage from the ischemic side showed a significant increase in HIF-1α protein level and HIF-1α expression. VEGF expression in the cartilage was dramatically and significantly increased at 24 h, 2 and 4 weeks (p < 0.05 for all) with 5 to 10 fold increase being observed on the ischemic side compared to the normal side. PECAM and VEGFR2 expressions in the cartilage were both significantly decreased at 24 h but returned to the normal levels by 2 and 4 weeks, respectively. Micro-CT showed revascularization of the cartilage on the ischemic side with the vessel volume/total volume equaling the normal side by 4 weeks.ConclusionsAcute ischemic injury to the immature femoral head induced severe hypoxia and cell death in the bony epiphysis and the deep layer of the epiphyseal cartilage. Viable chondrocytes in the superficial layer of the epiphyseal cartilage showed HIF-1α activation and VEGF upregulation with subsequent revascularization occurring in the cartilage.     

A solid-phase technique for preparation of no-carrier-added technetium-99m radiopharmaceuticals: application to the streptavidin/biotin system

A high effective specific activity (HESA) formulation of a biotin-containing ^99mTc ligand [RP488: dimethyl-Gly-Ser-Cys(Acm)-Lys(Biotin)-Gly] conveniently prepared from solid phase was compared to a typical low effective specific activity (LESA) solution formulation to demonstrate improved targeting to streptavidin in an in vitro assay and in an in vivo rat model. RP488 was coupled to a maleimide-functionalized polyethylene glycol resin via a thiol ether linkage and labeled with ^99mTc-gluconate at room temperature, followed by elution of the HESA ^99mTc-RP488 in saline (minimum specific activity 1000 TBq/mmol by amino acid analysis). Both HESA and LESA ^99mTc-RP488 labeled at > 90% purity. In vitro, HESA ^99mTc-RP488 incubated with streptavidin-agarose was bound quantitatively, but there was competition from addition of increasing amounts of cold RP488. In rats, radiotracer uptake was evident at the site of implantation of streptavidin-agarose beads for the HESA dose, less uptake of low effective specific activity (LESA) material, and no appreciable uptake in the control rats of the LESA or HESA dose. The target-to-background ratio for HESA ^99mTc-RP488 was 5.4 times that of the control. The solid-phase technology offers a convenient way to prepare high specific activity receptor-targeting ^99mTc radiopharmaceuticals.     

Early mobilization following angioplasty

AIM: To assess the incidence of puncture site complications in in-patients undergoing early mobilization following angioplasty with a view to performing day case angioplasty. MATERIALS AND METHODS: One hundred and twenty-eight patients undergoing peripheral and renal angioplasty using a sheath size of up to 6 French were recruited prospectively. The mobilization protocol consisted of supine bed rest for 2 h, followed by gradual mobilization, so that the patient was ambulant 4 h after the procedure. Mobilization was delayed if clinically appropriate. Puncture sites were scored for discomfort, paraesthesia, visible bruising and palpable haematoma after groin compression and the following morning. RESULTS: One hundred and forty-four puncture sites were studied. There were 44 haematomas in total, of which 37 (26%) were less than 2.5 cm and seven (4.9%) were between 2.5 cm and 7.5 cm. Four patients (2.8%) had visible bruising greater than 7.5 cm. No patient assessed discomfort higher than moderate at any stage. Mobilization was delayed in 15 patients. In 11 this was due to puncture site oozing, haematoma in one, two were hypertensive and one required surgery for limb ischaemia. All complications occurred within 4 h of angioplasty. No patient required surgery or transfusion for haemorrhagic complications. CONCLUSION: Mobilization at 4 h was successful in 90% of cases but 10% require more prolonged bed rest. No delayed complications occurred. These results suggest that day case angioplasty is feasible in most cases.Butterfield, J. S. (2000). Clinical Radiology55, 874-877 Copyright 2000 The Royal College of Radiologists.     

Kinematic analysis of conventional and high-flexion cruciate-retaining total knee arthroplasties: an in vitro investigation

This study examined the kinematics of a cruciate-retaining (CR) total knee arthroplasty (TKA) component that attempts to enhance knee flexion by improving posterior tibiofemoral articular contact at high-flexion angles. Using an in vitro robotic experimental setup, medial and lateral femoral translations of this CR design were compared with that of a conventional CR TKA design and intact knee under a combined quadriceps and hamstring muscle load. Both CR TKA designs showed similar kinematics throughout the range of flexion (0 degrees -150 degrees ). The TKAs restored nearly 80% of the posterior femoral translation of the intact knee at 150 degrees . The posterior cruciate ligament (PCL) forces measured for the high-flexion CR TKA component indicate that the PCL is important in the mid-flexion range but has little effect on knee kinematics at high flexion.     

Thyroid-stimulating hormone, thyroid hormones, and bone loss

It has become accepted by virtue of rich anecdotal experience and clinical research that thyrotoxicosis is associated with high-turnover osteoporosis. The bone loss, primarily due to accelerated resorption that is not compensated by a coupled increase in bone formation, has been attributed solely to elevated thyroid hormone levels. Evidence using mice lacking the thyroid hormone receptors α and β establishes a role for thyroid hormones in regulating bone remodeling but does not exclude an independent action of thyroid-stimulating hormone (TSH), levels of which are low in hyperthyroid states, even when thyroid hormones are normal, as after thyroxine supplementation and in subclinical hyperthyroidism. We show that TSH directly suppresses bone remodeling and that TSH receptor null mice have profound bone loss, suggesting that reduced TSH signaling contributes to hyperthyroid osteoporosis. TSH and its receptor could become valuable drug targets in treating bone loss.     

Training general surgery residents in pediatric surgery: educational value vs time and cost

Background

This study evaluated the educational value of pediatric surgery rotations, the likelihood of performing pediatric operations upon completing general surgery (GS) residency, and time and cost of training GS residents in pediatric surgery.

Methods

A survey was administered to GS residents that evaluated the pediatric surgery rotation and anticipated practice intentions. A retrospective analysis (2005-2006) of operative times for unilateral inguinal hernia repair, bilateral inguinal hernia repair, and umbilical hernia repair was also performed. Procedure times were compared for operations performed by a pediatric surgeon with and without GS residents. Cost analysis was based on time differences.

Results

General surgery residents (n = 19) considered the pediatric surgery rotation to have high educational value (4.7 ± 0.6 of 5) with extensive teaching (4.6 ± 0.7) and operative experience (4.4 ± 0.8). Residents listed pediatric surgery exposure, operative technique, and observed work ethic as most valuable. Upon graduation, residents expect to perform pediatric operations 2 to 3 times annually. Thirty-seven percent of residents felt competent to perform appendectomy (patients >5 years), 32% appendectomy (3-5 years), 21% gastrostomy (>1 year), and 11% inguinal herniorrhaphy (>1 year). Operative times and costs were significantly higher in operative procedures performed with a GS resident.

Conclusion

General surgery residents considered pediatric surgery as a valuable educational experience. Residents anticipate performing pediatric operations a few times annually. Training GS residents in pediatric surgery increased operative time and cost. This information may be useful in determining the appropriate setting for resident education as well as budget planning for pediatric surgical practices.     

Establishing a regional pediatric surgical service in the setting of universal health care: a glimpse into the future

Purpose

Increasing health care expense and rising numbers of uninsured Americans have led many to propose a national health insurance. This study describes the process, rationale, and requirements in creating a regional pediatric surgical service in the setting of a single-payer system.

Methods

Our health care system consists of 10 medical centers providing comprehensive care to more than 3 million members. All services are provided by salaried physicians/practitioners to prepaid members. Before July 2004, pediatric surgical care was performed at multiple medical centers with many services contracted out. Starting July 2004, a multidisciplinary, comprehensive pediatric perioperative plan was established. Implementation has occurred in steps; current status and preliminary results are reviewed.

Results

Strict guidelines for pediatric anesthesia and requirements for support services, personnel, and equipment were defined. Pediatric surgery is now performed at 3 community medical centers and 1 tertiary, teaching hospital. Operative cases were assigned to each center based on age, complexity, level of postoperative care, and location. A single high-volume, center for complex care has been established. Access to care was excellent; more than 90% of outpatient consultations were seen within 2 weeks. Utilization of services was 94% in 2006 and 98% in 2007. Physician and patient satisfaction were high. Additional pediatric surgeons have been hired and nearly all care has been internalized. Given the proximity to a major children's hospital, specialty services have not been duplicated.

Conclusion

Establishing a multidisciplinary, comprehensive pediatric perioperative plan provided standards for supporting pediatric surgical services at community hospitals. This regional service may be a model for the future of specialty care, especially in the setting of a single-payer system.     

Rehabilitation variability following medial patellofemoral ligament reconstruction

Background: Medial patellofemoral ligament (MPFL) reconstruction is an increasingly utilized surgical option for recurrent patellar instability. Recent studies have highlighted the potential benefits of accelerated functional rehabilitation; however, no validated MPFL rehabilitation guidelines currently exist.

Objective: To assess the variability of MPFL reconstruction rehabilitation protocols published online by academic orthopaedic programs.

Methods: Online MPFL rehabilitation protocols from U.S. teaching orthopaedic programs were reviewed. A comprehensive scoring rubric was developed to assess each protocol for both the presence of various rehabilitation components and the timing of their introduction.

Results: Thirty-one protocols (20%) were identified from 155 U.S. academic orthopaedic programs. Thirty protocols (97%) recommended immediate postoperative knee bracing. Twenty protocols (65%) allowed for weight-bearing as tolerated using crutches immediately postoperatively, whereas seven protocols (23%) recommended partial weight-bearing and four protocols (13%) recommended toe-touch weight-bearing. For those protocols advising partial and toe-touch weight-bearing, advancement to full weight-bearing was achieved at averages of 4.7 (range, 3–8) weeks and 6.3 (range, 6–7) weeks, respectively. There was considerable variation in range of motion (ROM) goals; however, most protocols (97%) recommended achieving 90 degrees of knee flexion at an average of 1.4 (range, 0–6) weeks. Significant diversity was found in the inclusion and timing of strengthening, stretching, proprioception, and basic cardiovascular exercises. Twenty-five protocols (81%) recommended return to training after completing specific athletic criteria.

Conclusions: A minority of U.S. teaching orthopaedic institutions publish MPFL reconstruction rehabilitation protocols online. Furthermore, there is a high degree of variability in both the composition and timing of rehabilitation modalities across these protocols.     

Book reviews

History

The End of History and the Last Man By Francis Fukuyama. Hamish Hamilton, London, 1992, 418 pp., £20.00, ISBN 0–24–1301–1

Aeskulap oder Mars? [Asdepius or Mars] (subtitle: Doctors against War) Edited by T.M. Ruprecht and C. Jenssen. (In German). Donat Verlag, Bremen, 1991, 604pp., 48.00DM, ISBN 3–924444–51‐X.

The Gulf War

Hidden Casualties, Volume II: The Environmental, Health and Political Consequences of the Persian Gulf War Edited by Saul Bloom, John M. Miller and Philippa Winkler, with Ross Mirkarimi. ARC/Arms Control Research Center, 942 Market St, Suite 202, San Francisco CA 94102, USA, 1993, 350pp.

Medicine and War

Wounded Healthy Cities: Searching for Health and Human Dignity A report by the Croatian Healthy Cities Network. Compiled by Ivana Eterovi?, Selma Sogori?, and Slobodan Lang. Edited by John Middleton. Sandwell Public Health Publications, 1992, PO Box 1953, Lyndon, West Bromwich, West Midlands, B71 4NA, pp. 68, £5.95 incl. p&;p, ISBN 0–9517035–4–4.

Public Health

Health through Public Policy, the Greening of Public Health Edited by Peter Draper. Greenprint, London, 1991, x + 258 pp., £9.99, ISBN 1–85425–045–0.

Economics

The Culture of Contentment By John Kenneth Galbraith. Sinclair Stevenson, London, 1992, 195pp., £14.95, ISBN 1–85619–147–8.

Beyond the Limits: Global Collapse or a Sustainable Future By Donella Meadows, Dennis Meadows and Jorgen Randers. Earthscan, London, 1992, xix + 300 pp., £19.95, ISBN 1–85383–130–1 (hbk), £11.95, ISBN 1–85383–131‐X (pbk).

Human Rights

Refugees: Rationing the Right to Life By David Keen. Zed Books, London, 1992, 86pp., £29.9S(hbk), ISBN 1–85649–091–2, £9.95(pbk), ISBN 1–85649–092–0.

Deadly Silence: Black Deaths in Custody Institute of Race Relations, London, 1991, 75pp., £4 (pbk), ISBN 085001–038–1.

Torture and Its Consequences: Current Treatment Approaches Edited by Metin Ba?o?lu. Cambridge University Press, Cambridge, 1992, xxiii + 527pp., £55.00, ISBN 0–521–39299–3

Militarism and the Environment

Taking Stock: The Impact of Militarism on the Environment Working Group on Militarism and the Environment. Science for Peace, 1992, 30pp., Can$ 4.00 (available from WGME, University College, University of Toronto, Ontario, Canada M5S 1A1).

AIDS

The AIDS Epidemic: Economic, Political and Security Implications By Alan Whiteside and David FitzSimons. Research Institute for the Study of Conflict and Terrorism, London, 1992, 43pp., £9.00, ISSN 0069–8792 (available from 136 Baker Street, London W1M 1FH)