Sheep recombinant IGF-1 promotes organ-specific growth in fetal sheep.

IGF-1 is a critical fetal growth-promoting hormone. Experimental infusion of an IGF-1 analog, human recombinant LR3 IGF-1, into late gestation fetal sheep increased fetal organ growth and skeletal muscle myoblast proliferation. However, LR3 IGF-1 has a low affinity for IGF binding proteins (IGFBP), thus reducing physiologic regulation of IGF-1 bioavailability. The peptide sequences for LR3 IGF-1 and sheep IGF-1 also differ. To overcome these limitations with LR3 IGF-1, we developed an ovine (sheep) specific recombinant IGF-1 (oIGF-1) and tested its effect on growth in fetal sheep. First, we measured in vitro myoblast proliferation in response to oIGF-1. Second, we examined anabolic signaling pathways from serial skeletal muscle biopsies in fetal sheep that received oIGF-1 or saline infusion for 2 hours. Finally, we measured the effect of fetal oIGF-1 infusion versus saline infusion (SAL) for 1 week on fetal body and organ growth, in vivo myoblast proliferation, skeletal muscle fractional protein synthetic rate, IGFBP expression in skeletal muscle and liver, and IGF-1 signaling pathways in skeletal muscle. Using this approach, we showed that oIGF-1 stimulated myoblast proliferation in vitro. When infused for 1 week, oIGF-1 increased organ growth of the heart, kidney, spleen, and adrenal glands and stimulated skeletal myoblast proliferation compared to SAL without increasing muscle fractional synthetic rate or hindlimb muscle mass. Hepatic and muscular gene expression of IGFBPs one to three was similar between oIGF-1 and SAL. We conclude that oIGF-1 promotes tissue and organ-specific growth in the normal sheep fetus.

The role of the fibula head flap for joint reconstruction after osteoarticular resections.

INTRODUCTION AND AIM: Endoprosthetic reconstruction is considered the mainstay of limb salvage in periarticular bone tumours. However, this procedure has limited durability especially when performed in young patients. The free fibula head flap including the proximal articular surface represents one option for hemiarthroplasty reconstruction. The aim of this study was to investigate the role of the fibula head flap for joint reconstruction after osteoarticular resections. PATIENTS AND METHODS: All patients who underwent hemiarthroplasty procedures between 2000 and 2006 using the free fibula head flap were included in the study. Functional assessments were performed using the American Musculoskeletal Tumor Society (AMTS) classification. RESULTS: There were five males and two females (mean age: 22.6 ± 15.9 years). Five patients underwent reconstruction following resection of malignant bone tumours and two for chronic osteomyelitis of the distal humerus. In three patients, the fibula was used for distal radius and wrist joint reconstruction, and the remaining four patients for reconstruction of the distal humerus and elbow joint. A vascularised growth plate transfer based on the lateral geniculate vessels was performed in two patients. Atechnetium-bone scan confirmed viability of all flaps 10 days after surgery, and radiographic bony union was confirmed on average 5 months following surgery. There were no complications with the recipient or donor site after a median follow-up of 71 months (range: 12 months to 10 years). All patients achieved reasonable return of function and were able to perform all activities of daily living. CONCLUSIONS: We demonstrate that the hemiarthroplasty procedure using the free fibula flap with its proximal head is a safe procedure with good functional results. Performing autologous arthroplasty using a free fibula head flap may be a promising alternative to an endoprosthesis or alloplastic reconstruction with a low risk of complications and morbidity.

Periodontal bone loss associated with an improper flossing technique: a case report.

PURPOSE: This article documents a case in which soft tissue and bone damage was associated with a long-standing habit of improper flossing. CASE DESCRIPTION: A 33-year-old patient with excellent oral hygiene presented with gingival clefting and an unusual pattern of moderate angular bone loss at several sites. Previous radiographs suggested that some bony lesions had been present for more than 13 years. Examination revealed no evidence that the osseous defects were related to chronic periodontitis or occlusal trauma. The focus of treatment for these chronic injuries was teaching the patient an atraumatic flossing technique. CONCLUSION: As the lesions had gone undiagnosed for many years, this case underscores the need to look for clinical signs of floss-induced damage during periodic examinations.

Thyroxine transfer and distribution in critical nonthyroidal illnesses, chronic renal failure, and chronic ethanol abuse.

Serum T4 kinetic studies were performed in euthyroid patients with acute critical illnesses, chronic renal failure, or ethanol abuse without overt hepatocellular damage and in healthy euthyroid subjects with normal or altered serum T4 binding to determine the relative effects of altered serum T4 binding and extravascular disturbances on T4 transfer and distribution in nonthyroidal illnesses. A three-pool model with rapidly and slowly equilibrating pools exchanging with serum was used to evaluate the potential sites of alterations. Healthy euthyroid subjects with low serum T4-binding globulin levels had increased serum percent free fraction of T4 (%FFT4) and fractional T4 transfer rates (FTR) from serum to both extravascular pools, while those with high serum T4-binding capacity had decreased %FFT4 and FTR from serum to the rapid pool and increased T4 binding in the slow pool. Critically ill patients had significantly reduced serum total T4 (TT4) with increased %FFT4 but decreased FTR from serum to both extravascular pools and reduced T4 binding in the slow pool. Patients with ethanol abuse had normal serum TT4 and %FFT4 but significantly increased FTR from serum to the rapid pool and increased binding in both extravascular pools. Chronic renal failure patients had no alterations in any of these values. The T4 FTR from serum to both extravascular pools were directly related to the serum %FFT4 in healthy subjects and inversely related in the patients. Further, the FTR from the rapid pool to serum were inversely related to rapid pool binding in healthy subjects but not in the patients, while the FTR from the slow pool to serum were unrelated to slow pool binding in both groups. These findings indicate that in patients with nonthyroidal illnesses the transfer of T4 between serum and the extravascular pools is not primarily a reflection of T4 binding to serum binding proteins or extravascular sites. Further, alterations in slow pool binding may be affected by changes in T4 binding to serum binding proteins, which are known to be present in the interstitial fluid of these tissues. Finally, the type and magnitude of the alterations in T4 transfer and distribution in patients with nonthyroidal illnesses appear to differ for rapidly and slowly equilibrating tissues and may be related to the etiology and/or severity of the nonthyroidal disorder.