Double aortic arch associated with esophageal atresia and tracheoesophageal fistula

Esophageal atresia (EA) with tracheoesophageal fistula (TEF) is commonly associated with significant cardiovascular anomalies. Mortality is higher with cardiovascular abnormalities, especially those undiagnosed prior to surgical repair of the EA/TEF. Advances in cardiac imaging techniques, most notably echocardiography, have made noninvasive evaluation of the heart and great vessels easy to perform and reliable. Thus, the preoperative cardiovascular anatomy of these infants should be routinely assessed prior to surgical correction. A case of EA/TEF associated with an unsuspected double aortic arch is described. Although a wide variety of cardiovascular lesions have been associated with EA/TEF, coexistence of a double aortic arch has not been previously reported. Preoperative recognition of this anomaly would have altered the surgical approach, and perhaps reduced the postoperative morbidity and mortality.     

A phase I Study with oral SU5416 in patients with advanced solid tumors: A drug inducing its clearance

Summary Vascular endothelial growth factor (VEGF) is a potent stimulant of angiogenesis. SU5416, is a small molecule tyrosine kinase inhibitor, and a potent inhibitor of VEGF- mediated Flk-1 receptor signaling. Intravenous agent SU5416 has shown evidence of biological activity against a variety of tumor types. The current intravenous dosing regimen is not optimal for long-term administration, which is needed for optimal efficacy. The aim of this study was to evaluate the safety profile and pharmacokinetics of a Nanocrystal Colloidal Dispersion^TM (NCD) SU5416 formulation in humans. Patients with advanced and/or metastatic solid organ tumors were included in the trial; various SU5416 regimens were tested for tolerability, safety and were evaluated concerning pharmacokinetics. The results of this study indicate that induction of clearance after oral dosing of NCD SU5416 in humans occurs and is greater than following IV administration. It has been confirmed that SU5416 is a high clearance compound, also as an oral NCD formulation. The NCD formulation was well tolerated, but no effective drug serum levels could be achieved. These data help to understand the ADME (Absorption, Distribution, Metabolism, Excretion) properties of indoline chemical class compounds. The lessons learned should be applied in the development of next generation indoline anti-angiogenic and anti-tumor compounds.     

Specific antigrowth effect of interferon on mouse cells transformed by murine sarcoma virus

The growth rate of NIH/3T3 mouse fibroblasts transformed by the Moloney strain of murine sarcoma virus was investigated following interferon (IFN) treatment. These cells were found to be sensitive to the antigrowth effect of IFN as indicated by a slower growth rate in its presence. The effect was most efficiently expressed when cells were grown at low serum concentrations, e.g., 2.5%. Likewise, IFN treatment caused a reduction in the rate of DNA synthesis as measured by [3H]thymidine incorporation. In contrast, these effects were observed only to a very minor extent with uninfected NIH/3T3 cells or with NIH/3T3 cells chronically infected with murine leukemia virus. In addition, IFN treatment significantly decreased the cloning efficiency of murine sarcoma virus-transformed cells in semi-solid agar. Furthermore, an even stronger effect on the cloning efficiency was observed in liquid medium supplied with 2.5% serum, indicating a direct inhibitory effect on the growth of these cells. Under these conditions, NIH/3T3 or NIH/3T3(MLV) cells remained unaffected by IFN treatment, nor was this effect evident when the transformed cells were grown in the presence of 10% serum. A 4-fold increase in the level of (2'-5')oligoadenylate synthetase following IFN treatment was observed in murine sarcoma virus-transformed cells as compared to either NIH/3T3 or NIH/3T3(MLV) cells.     

Protective effect of cholesterol on Friend leukemic cells against photosensitization by hematoporphyrin derivative

The cytotoxic effects of hematoporphyrin derivative (HPD) on Friend erythroleukemic cells were studied. Upon binding of the porphyrin to the cells, the fluorescence spectra was shifted from 613 to 633 nm regarding the main band and from 676 to 667 nm concerning the secondary band. The kinetics of HPD binding was then determined. Maximum binding already occurred at 60 s after exposure of the cells to HPD. It could be demonstrated that the effect of the photoactivated HPD on cell viability was drug, dose, and light fluorescence dependent. Cellular protein synthesis and Friend virus complex release from the cells were equally inhibited by the photodynamic sensitization of the drug, indicating no specific effect on virus maturation. Since cholesterol affects the fluidity of cell membranes, it was important to study the effect of cholesterol enrichment on the photodynamic sensitization by HPD. It was found that, while a 50% reduction in protein synthesis was monitored following treatment with 20 micrograms of HPD per ml and illumination by a 6-milliwatt white light for 60 s, no inhibition was observed following preenrichment of the cells with 0.5, 1, or 2% of cholesterol hemisuccinate. The same trend of cholesterol protection was demonstrated with longer illumination periods up to 10 min. The protective effect of cholesterol hemisuccinate was also seen using scanning electron microscopy. It is thus concluded that the cholesterol hemisuccinate content of Friend erythroleukemic cell membranes is an important factor in regulating the cytotoxicity of photoactivated HPD.     

Fetal intracranial teratoma: US diagnosis of three cases and a review of the literature

We describe three cases of fetal intracranial teratoma diagnosed by ultrasound and review the literature. Sonographic features include cranial enlargement, gross distortion of normal cerebral architecture by a hyperechoic, multicystic mass, and polyhydramnios. Despite early diagnosis, the cesarean section rate is high and the overall prognosis is dismal.