Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone

Balla P, Moskovszky L, Sapi Z, Forsyth R, Knowles H, Athanasou N A, Szendroi M, Kopper L, Rajnai H, Pinter F, Petak I, Benassi M S, Picci P, Conti A & Krenacs T
(2011) Histopathology 59 , 376–389 Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone Aims: Epidermal growth factor receptor (EGFR) is implicated in bone remodelling. The aim was to determine whether EGFR protein expression contributes to the aggressiveness and recurrence potential of giant cell tumour of bone (GCTB), an osteolytic primary bone tumour that can exhibit markedly variable clinical behaviour. Methods and results: Immunohistochemical analysis on tissue microarrays (TMA) of 231 primary, 97 recurrent, 17 metastatic and 26 malignant GCTBs was performed using TMA analysis software and whole digital slides allowing validated scoring. EGFR expression was restricted to neoplastic stromal cells and was significantly more frequent in recurrent (71 of 92; 77%) than in non‐recurrent GCTBs (86 of 162; 53%) (P = 0.002); and in clinicoradiologically aggressive (31 of 43; 72%) than latent (27 of 54; 50%) cases (P = 0.034). Detecting phosphotyrosine epitopes pY1068 and ‐pY1173 indicated active EGFR signalling, and finding EGFR ligands EGF and transforming growth factor‐α restricted to cells of the monocytic lineage suggested paracrine EGFR activation in stromal cells. In functional studies EGF supported proliferation of GCTB stromal cells, and the addition of EGF and macrophage‐colony stimulating factor promoted osteoclastogenesis. Conclusion: In GCTB, EGFR signalling in neoplastic stromal cells may contribute to disease progression through promoting stromal cell proliferation and osteoclastogenesis.     

Small intestinal transplantation

The purpose of this study was to determine whether small intestinal transplantation could be considered as an alternative in the treatment of patients suffering from the short-bowel syndrome. The site of absorption of oral cyclosporine A was determined as were the changes that follow small intestinal transplantation. The interactions between the lipophilic cyclosporine A molecule and fat emulsion solutions used for total parenteral nutrition were investigated. Finally, a technique for harvesting the entire small bowel in man was developed. The absorption of oral cyclosporine A in normal dogs, and in bowel-resected, autotransplanted, and allotransplanted dogs was determined. Cyclosporine A levels were monitored in all animals. This demonstrated that cyclosporine A is absorbed through the small bowel and carried through the lymphatics; that absorption is decreased to 40 percent of normal after autotransplantation or allotransplantation without rejection. Rejection further hampers cyclosporine A absorption. Administration of olive oil alone enhances absorption of cyclosporine A. We also administered cyclosporine A IV to five dogs, with and without a concomitant infusion of fat emulsion solution (Intralipid). No changes in plasma cyclosporine A levels, in the clearance of cyclosporine A, or in the in vivo distribution of cyclosporine A were noted. Finally, dissections in six cadavers and in four brain-dead organ donors were performed, and a reproducible technique for harvesting the small bowel in man was established. In selected patients with the short-bowel syndrome, small intestinal transplant may be considered as an alternative therapy to home total parenteral nutrition.     

Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis and collagen organization during Achilles tendon healing

BACKGROUND: In the last few years much research has been conducted in methods to promote tendon healing. The aim of this study was to determine if the healing process after operative repair of rat Achilles tendons could be stimulated by the paratendinous injection of a sensory peptide, substance P (SP). METHODS: Ninety-six male Sprague-Dawley rats were randomly allocated to four groups: (I) control buffer injections, (II) injections of SP 10(-6) mol/kg body weight combined with a carrier, (III) injections of SP 10(-8) mol/kg BW with the carrier, and (IV) injections with the carrier only (thiorphan 1 micromol/kg BW and captopril 30 micromol/kg BW, both neutral endopeptidase inhibitors). The influence on tissue repair was determined from the histologic measurement of fibroblast proliferation, angiogenesis, and collagen organization. On days 7, 14, 28 and 42, animals were sacrificed and histologic evaluations were performed on the injured Achilles tendon constructs. RESULTS: The two groups subjected to SP injections showed a significant initial fibroblast proliferation on day 7 (p < 0.05), which rapidly declined by day 14 to the level of cellular proliferation observed with the use of thiorphan and captopril. Capillary proliferation showed a similar evolution, except that in the second week angiogenesis in the treated groups was below the level of the control group. Strikingly, collagen orientation increased faster in the groups injected with SP. This was obvious from the second week already and the difference remained until the completion of the study. CONCLUSION: This is the first study to demonstrate that paratendinous injections of SP after operative repair of the Achilles tendon in rats appears to provide a boost to the initial stages of healing and significantly accelerate the reparative phase of the healing process.     

Right Atrial Thrombus Mimicking a Myxoma: Synergism of Hormonal Contraceptives and Antiphospholipid Antibodies

Cardiac thrombus, the most common intracardiac mass, is typically seen in the left side of the heart in the presence of atrial fibrillation, mitral stenosis, or impaired global wall motion. Right atrial thrombus, which is rarer, is usually associated with central venous catheter placement or pulmonary embolism. We present the case of a 24-year-old woman with a history of mitral valve prolapse who presented with fatigue and palpitations. Echocardiograms and cardiac magnetic resonance images revealed a right atrial mass compatible with a myxoma. However, after surgical excision of this and a second mass discovered intraoperatively, pathologic evaluation confirmed organized thrombus rather than myxoma.The patient''s only risk factor was her use of oral contraceptive pills. Test results for hypercoagulable disorders revealed the presence of antiphosphatidylserine, an uncommon antiphospholipid antibody. The patient stopped taking the contraceptive. This case suggests the need to examine further the role of antiphosphatidylserine antibodies in the diagnosis of antiphospholipid syndrome.     

Spontaneous Multivessel Coronary Spasm During Diagnostic Coronary Angiography

Acute vasospastic angina, formerly known as Prinzmetal angina, is characterized by transient electrocardiographic changes that are not related to exertion. Its atypical presentation makes it difficult to establish the diagnosis, so it is probably underrecognized and therefore mismanaged. We treated a 49-year-old woman who presented with a 2-day history of chest pain associated with palpitations. Abnormal radionuclide stress test results prompted diagnostic coronary angiography, during which the patient reported chest pain and became hemodynamically unstable. Active coronary vasospasm at multiple sites was treated with intracoronary nitroglycerin and nicardipine, leading to immediate recovery.Our case highlights the importance of accurate, timely diagnosis of vasospastic angina, and of early recognition and management of spontaneous coronary spasm during angiography.     

Meals identified as healthy choices on restaurant menus: an evaluation of accuracy

This study evaluated the accuracy of restaurant entrees identified as healthy choices on menus at two fast food restaurant chains. Entrees were purchased at two different locations of each restaurant 35 days apart. Samples were processed in duplicate for total fat contents, sodium analysis, and adiabatic bomb calorimeter for total energy. t-Tests compared a) the mean experimental values to claimed values for fat, energy, and sodium, b) nutritional content at different locations for the same restaurant, and c) the mean experimental values for fat, energy, and sodium levels to the recommended Daily Values. Results indicate that entrees identified as healthy choices at these selected restaurants are in fact healthy choices, are accurately labeled, and are consistent among different locations of the same restaurant chains.