Using orbital sonography to diagnose and monitor treatment of acute swelling of the eyelids in pediatric patients

OBJECTIVE. Clinical signs of acute erythematous swelling of the periorbital region may be related either to benign superficial inflammation or to the more severe and potentially life-threatening condition of orbital infection. CONCLUSION. We recommend orbital sonography in every child with periorbital swelling and erythema. In contrast to superficial infection in which edematous swelling of the eyelid can be documented without lesions of the orbital content, either a hyper- or a hypo-echoic mass displacing the medial rectus muscle laterally is highly suggestive of orbital infection. Introducing sonography into early diagnostic interventions in pediatric patients avoids delaying appropriate treatment and allows disease monitoring on a daily basis.     

Tyrosine kinase inhibitors and gemcitabine: new treatment options in pancreatic cancer?

Pancreatic cancer (PCa) is one of the most lethal malignancies in humans. Gemcitabine is the current standard chemotherapy of advanced PCa but it is still far from optimal and novel therapeutic strategies are urgently needed. For the near future, tyrosine kinase inhibitors (TKIs) hold great promise as a therapeutic strategy. Tyrosine kinases (TKs) play a pivotal role in intercellular signal transduction and regulate crucial processes of tumor cells such as proliferation, migration, survival and angiogenesis. Several TKs--such as EGFR, VEGFR, PDGFR and Src--are known to be overexpressed or constitutively activated in PCa. Hence, blocking receptor tyrosine kinases (RTKs) and non-receptor, cytoplasmic tyrosine kinases (CTKs) represents a rational approach to treat PCa. In particular, cetuximab and erlotinib, the monoclonal antibodies against EGFR-1 (ErbB-1) showed promising activity in Phase II and Phase III trials and their combination with gemcitabine resulted in synergistic antitumor activity. In addition, small antiangiogenic molecules such as VEGFR-2 inhibitors, PDGFR inhibitors and multiple receptor targeting agents are under active investigation. Association of chemoresistance with the activity of certain tyrosine kinases (e.g. ErbB-1 and Src) has been described for pancreatic cancer and makes a strong case for combining gemcitabine with TKIs. Combinations of different TKIs might also be used to target the cancer cell micro-environment. Detailed molecular characterization of tumor cells and combinations of appropriate TKIs with cytotoxic agents such as gemcitabine are expected to lead to improved therapy of pancreatic cancer.     

Amplitude envelope correlation detects coupling among incoherent brain signals

Cognitive processing involves gamma-activation over broad cortical regions. Phase coupling of these activities has rarely been reported for areas far apart. Other forms of coupling are generally not detected by conventional measures. Here, we use amplitude envelope correlation (AEC), which can detect signal coupling without phase coherence, even among different frequencies. We apply it to subdural recordings from humans performing a visual delayed match-to-sample task and systematically compare it with spectral amplitude and coherence. The different measures often show divergent results. In particular, AEC reveals y-coupling completely missed by coherence. We argue that coherence and AEC are adapted to different cortical mechanisms of short- and long-range interactions, respectively.     

Clinical presentations of infection by the human herpesvirus-7 (HHV-7)

Reports on the clinical picture of primary infection with the human herpesvirus-7 (HHV-7) are scarce. A heterogenous population of 478 patients (1 month-14 years) was examined for the presence of an acute HHV-7 infection. A variety of clinical pictures can be observed during primary infection with HHV-7, such as exanthema subitum and mononucleosis-like syndrome. The authors describe in two children, for the first time, the presentation of HHV-7-infection as an acute exacerbation or relapse of a patient's chronic disease. The hematological changes for the respective clinical presentations during HHV-7 infection are reported.     

Clearance of inert molecules, Na, and Cl ions across the primate placenta

Transplacental clearances of antipyrine, tritiated water, urea, Na, and Cl ions were studied in the rhesus monkey. In order of decreasing placental permeability determined in vivo, these experiments showed the following order: tritiated water and antipyrine, urea, chloride, and sodium ions. Clearances of tritiated water and antipyrine were equal. The placental clearances of tritiated water and antipyrine were significantly different when determined across the chorion laeve in vitro. These observations suggest that the transplacental diffusion of these molecules is flow limited. The diffusion rates of urea, Na, and Cl ions were limited primarily by the permeability of the placental membrane. The placenta of the rhesus monkey is more permeable to Na and Cl ions than the sheep placenta. Permeability to urea per kilogram of fetal body weight is of the same order of magnitude in both species.     

The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-dPhe1,Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumours

Somatostatin receptor-expressing tumours are potential targets for therapy with radiolabelled somatostatin analogues. We have synthesized a number of such analogues in the past and identified [DOTA-dPhe¹, Tyr³]octreotide (SMT 487) as the most promising candidate molecule because of its advantageous properties in cellular and in vivo tumour models. In the current paper we describe the radiotherapeutic effect of yttrium-90 labelled SMT 487 in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumour CA 20948. SMT 487 binds with nanomolar affinity to both the human and the rat somatostatin receptor subtype 2 (sst₂) (human sst₂ IC₅₀=0.9 nM, rat sst₂ IC₅₀=0.5 nM). In vivo, ⁹⁰Y-SMT 487 distributed rapidly to the sst₂ expressing CA 20948 rat pancreatic tumour, with a tumour-to-blood ratio of 49.15 at 24 h post injection. A single intravenous administration of 10 mCi/kg ⁹⁰Y-SMT 487 resulted in a complete remission of the tumours in five out of seven CA 20948 tumour-bearing Lewis rats. No regrowth of the tumours occurred 8 months post injection. Control animals that were treated with 30 μg/kg of unlabelled SMT 487 had to be sacrificed 10 days post injection due to excessive growth or necrotic areas on the tumour surface. Upon re-inoculation of tumour cells into those rats that had shown complete remission, the tumours disappeared after 3–4 weeks of moderate growth without any further treatment. The present study shows for the first time the curative potential of ⁹⁰Y-SMT 487-based radiotherapy for somatostatin receptor-expressing tumours. Clinical phase I studies with yttrium-labelled SMT 487 have started in September 1997. Received 14 January and in revised form 16 March 1998