Surgical treatment of hemangiomas and vascular malformations in functional areas

Hemangiomas and vascular malformations (VM) in functional areas can be treated by a variety of methods. Because of the natural involution of hemangiomas, a non-agressive approach is recommended. Active therapy is necessary only in cases where a function is affected such as vision, respiration, hearing, and feeding. Psychological problems can be an indication for early excision, and psychological/cosmetic reasons in the presence of fibrofatty tissue residues when the hemangioma has been involuted for late excision. In contrast to hemangiomas, no involution is to be expected for VMs, so that therapy depends mainly on the occurrence of functional problems and/or serious complications. Surgical excision still has a place, however, the indications are limited.     

Measurement of cerebral vascular extraction fractions in the rat using intracarotid injection techniques

A small volume (5 μl) common carotid arterial injection method is described for the quantitation of cerebral vascular extraction fractions (E_t) of diffusion limited tracer molecules in the rat. The method is a modification of a technique diffusion duced by Oldendorf and widely used for the study of blood-brain barrier phenomena. While the Oldendorf technique has proven valuable for estimating the relative permeabilities of substances, it is limited in measuring E_t under conditions of physiologically or pharmacologically altered permeability or blood flow. The method described in this paper — using a small volume (5 μl) common carotid injection, a freely diffusible reference tracer, [¹⁴C]butanol, and a 5 sec circulation time — allows for measurements of E_t that reflect changes in blood flow and small differences in permeability. The modified method is important for the study of the regulation of cerebral vascular permeability and flow in an inexpensive animal model.     

In Vitro Production of Mouse Mammary Tumor Virus in a Mouse Mammary Tumor Ascites Line

An ascites line derived from a spontaneous mouse mammary carcinoma produces, on explantation and cultivation in vitro, large amounts of oncornavirus particles. The biochemical, biophysical, and electron microscopic characteristics of the virions are described. Molecular hybridization and immunological methods identify these virions as mouse mammary tumor virus.     

Liver imaging in the diagnosis of hepatic venous thrombosis in paroxysmal nocturnal hemoglobinuria.

Eleven patients with paroxysmal nocturnal hemoglobinuria were studied by serial liver imaging. This disease has a generalized thrombotic tendency, and progressive diffuse hepatic venous thrombosis has been emphasized in recent studies. Radionuclide imaging proved to be of great help in establishing the diagnosis of hepatic venous thrombosis and following the progress of the disease process. Abnormal patterns in hepatic venous occlusion include (a) enlargement of the liver (especially the right lobe), (b) extrahepatic localization of radionuclide, and (c) areas of decreased uptake in the distribution of the involved veins. These findings develop rapidly and are very characteristic in the clinical setting.     

Perceived life-stress and psychopathology among mothers of young children.

Mentally ill mothers of young children, contrasted with well mothers, reported greater stress in their own lives, and in those of their husbands and parental families. Within each group of mothers, there was a different relationship between life-stress and psychological symptoms. Within the mentally ill group, stress was associated with both diagnosis and chronicity.     

Novel Phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416.

PURPOSE: To determine the biological modulatory dose of SU5416, we employed a novel trial design, where "dose de-escalation" was based on demonstrable biological changes observed at the maximum tolerated dose. If such an effect was shown, dose de-escalation to a predefined dose level would occur to determine if the lower dose exhibited the same amount of pharmacodynamic effect as the higher dose. EXPERIMENTAL DESIGN: Ten patients with advanced solid tumors were enrolled at each dose level. One of the following pharmacodynamic effects was considered significant: (a) a 35% decrease in microvessel density in sequential tumor biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, and plasma vascular endothelial growth factor were measured sequentially. RESULTS: Nineteen patients were enrolled. Sequential tumor biopsies in all evaluable patients showed an increase in microvessel density. Only one patient met the intended pharmacodynamic end point of >35% reduction in blood flow. There was a significant increase in both soluble E-selectin and soluble intercellular adhesion molecule levels pretreatment versus levels at the time of removal of patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum fibrinogen rose with therapy. There was a trend toward increase in plasma vascular endothelial growth factor levels. CONCLUSION: SU5416 does not result in decreased blood flow in tumors or a decrease in microvessel density. This corresponds to the lack of clinical activity seen with this agent. Our clinical trial design termed dose de-escalation is a novel approach to determine the in vivo biological effects of targeted therapies in cancer patients.