Insulin-like growth factor-1 receptor acts as a growth regulator in synovial sarcoma.

Synovial sarcomas account for 5-10% of all soft tissue sarcomas and the majority of synovial sarcomas display characteristic t(X;18) translocations that result in enhanced transcription of the insulin-like growth factor-2 (IGF-2) gene. IGF-2 is an essential fetal mitogen involved in the pathogenesis of different tumours, leading to cellular proliferation and inhibition of apoptosis. Here we asked whether activation of IGF signalling is of functional importance in synovial sarcomas. We screened human synovial sarcomas for expression of IGF-2 and the phosphorylated IGF-1 receptor (IGF-1R), which mainly mediates the proliferative and anti-apoptotic effects of IGF-2. Since both the phosphatidylinositol 3'-kinase (PI3K)-AKT pathway and the MAPK signalling cascade are known to be involved in the transmission of IGF-1R signals, expression of phosphorylated (p)-AKT and p-p44/42 MAPK was additionally assessed. All tumours expressed IGF-2 and 78% showed an activated IGF-1R. All tumours were found to express p-AKT and 92% showed expression of activated p44/42 MAPK. To analyse the functional and potential therapeutic relevance of IGF-1R signalling, synovial sarcoma cell lines were treated with the IGF-1R inhibitor NVP-AEW541. Growth was impaired by the IGF-1R antagonist, which was consistently accompanied by a dose-dependent reduction of phosphorylation of AKT and p44/42 MAPK. Functionally, inhibition of the receptor led to increased apoptosis and diminished mitotic activity. Concurrent exposure of selected cells to NVP-AEW541 and conventional chemotherapeutic agents resulted in positive interactions. Finally, synovial sarcoma cell migration was found to be dependent on signals transmitted by the IGF-1R. In summary, our data show that the IGF-1R might represent a promising therapeutic target in synovial sarcomas.

The many faces of aortoenteric fistulas.

Aortoenteric fistulas represent a life-threatening complication of abdominal aortic surgery that is becoming increasingly well-recognized. The presentation is often subtle, with a herald bleed followed by a period of grace, followed by an exsanguinating hemorrhage, and resulting in cardiovascular collapse. The diagnosis is often difficult, even with modern modalities of endoscopy, arteriography, and CAT scanning. A high index of suspicion is critical for making a successful diagnosis. The fistulas most commonly occur between the proximal aortic suture line and the duodenum after abdominal aortic surgery for aneurysmal or occlusive disease. Typically they occur years after this procedure. However, over the last several years, we have seen 12 cases with extremely unusual presentations that illustrate the wide spectrum of possible presentations. Included in this group was a primary aortoduodenal fistula, and two fistulas occurring just months after the initial surgery. These cases are reported with attention to the details of the presentation to emphasize the wide range of presentations of this serious complication. A brief review of this literature is also included in the report.

A new approach to the management of infected pacemakers.

Management of infected pacemakers always presents a problem. This report describes a method of managing infected pacemakers, using the infected unit as a temporary pacer. This method has worked well in four patients.

Tax-exempt yardstick: defining the measurements.

Congress, the Internal Revenue Service (IRS), and state and local governments still are trying to determine requirements a hospital must meet to warrant tax exemption. Revisions to a bill introduced by Rep. Brian Donnelly (D-Mass.) likely will focus Congressional debate on whether charity care or the broader concept of community benefits is the most appropriate measure for not-for-profit hospitals to meet; the IRS may develop intermediate sanctions it could impose on errant not-for-profit facilities in lieu of a total revocation of tax-exempt status; and perhaps the most stringent clamp-down on healthcare facilities' tax-exempt status will come from state and local governments that develop boundaries for tax-exempt hospitals to maintain. Not-for-profit facilities can respond to increased scrutiny by viewing government challenges as opportunities to "tell their stories" about charity care and community benefits.

A method of retraction during reoperative coronary operations using the Favaloro retractor.

A method is described for using the Favaloro retractor to provide retraction during dissection of the anterior wall of the heart during reoperative cardiac operations.

Congress inches toward a national policy on long-term care.

Although the growing demand for long-term care services calls for a comprehensive national policy, Congress has dealt with the issue in a piecemeal fashion. Sweeping changes have been deferred from year to year, amid considerable debate. Long-awaited action is expected in 1990, however, with four major bills on financing long-term care pending in Congress and recommendations due from a bipartisan commission.

[Hemangioblastomas of the central nervous system. A clinical study]. / Hämangioblastome des Zentralnervensystems. Eine klinische Studie.

In a survey of 46 patients with haemagioblastoma of the CNS (Neurology Dept. University Hamburg, 1950-1980) most (n = 40) were found to have angioblastomas of the cerebellum (Lindau tumors). Of these patients 21 were re-examined in 1983. Headache was the most frequent initial symptom (43%), and within this group one-third (10%-15%) had dizziness, sensorymotor deficits and cerebellar gait disturbances. Signs of elevated intracranial pressure much more often led to the correct diagnosis than dizziness or dystaxia. After the introduction of CCT to the diagnostic procedure the combined evaluation of angiography of the vertebral arteries and CCT always permitted the correct diagnosis. The low neurosurgical mortality rate (13.5%) has decreased to 0% within the last decade. No relapses were found in 21 re-examinations including CCT and EOG compared to a frequency of 9.7% in all 46 cases. Significantly less often than expected from other data we found: signs of possible hereditary influence (0%), multiple tumor localization combined with angiomatosis retinae (0%), polyglobulia (10.8%). Psychopathologically relevant signs (45.6%) were, in all cases, combined with signs of increased intracranial pressure. The results of our re-examination demonstrate that late postoperative deficits as well as possible relapses are earlier and more precisely evaluated by the combined use of clinical examination, CCT and EOG.