Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome.

BACKGROUND AND PURPOSE: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia. MATERIALS AND METHODS: Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities. RESULTS: Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. CONCLUSIONS: The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.

Examination of expanded polytetrafluoroethylene wound healing models.

The object of this animal study was to examine and further develop the expanded polytetrafluoroethylene wound healing model. The goal was to increase its potential for assessing wound healing by increasing yield, reducing variability, establishing the elements of a standard technique, and further testing its ability to detect variations of healing which have clinical significance. Expanded polytetrafluoroethylene implants of various dimensions and fabrications and several implantation and sterilization techniques were compared in rats. Hydroxyproline, DNA, and protein deposition into the expanded polytetrafluoroethylene implants as parameters for wound healing were assessed. Additionally, a 4 cm skin incision for tensile strength assessment was created. Wound healing was assessed under normal and corticosteroid-impaired healing conditions. The highest yield of collagen was found in the stiffer fabrication of expanded polytetrafluoroethylene with the larger pore size and after the more traumatic implantation technique of incisional placement. Variability was unaffected by fabrication, implantation technique, indexing by various geometric dimensions of the implant, sterilization, or sampling techniques. Variability was the same in the individual animals as in groups of animals. The expanded polytetrafluoroethylene method also detects the influence of antiinflammatory corticosteroids and reflects the tensile strength of incisional wounds made in other sites in the same animal.

Peptides from live yeast cell derivative stimulate wound healing.

Live yeast cell derivative is an alcoholic extract from yeast (Saccharomyces cerevisiae) that has previously been shown by three groups of workers to stimulate wound healing. Live yeast cell derivative is a complex mixture, and it was not known which of its many components was responsible for the biological activity. This study describes the separation and analysis of the major components, one of which is a peptide fraction that stimulates wound healing. The fraction consists of a mixture of peptides from 6000 to 17,000 d. It causes angiogenesis in a chick embryo yolk sac membrane assay and in a rabbit cornea assay, and it dramatically stimulates wound healing in the "Schilling/Hunt" wire mesh cylinder model at concentrations 25-fold lower than those required for the intact live yeast cell derivative.

Directly measured tissue oxygen tension and arterial oxygen tension assess tissue perfusion.

Mean subcutaneous tissue PO2 (PsqO2) measurements were obtained in dogs with an unheated electrode placed in an implanted Silastic tonometer, while PaO2 was increased in increments from 40 to 600 torr during normal, increased, and reduced blood volume. These changes reflect that the mean PsqO2 is approximately 10 torr below the PO2 of venous blood draining that tissue. Since PaO2 was already known, the oxygen content of arterial and venous blood entering and leaving this tissue could be determined by reference to blood-oxygen dissociation curves. Therefore, relative changes in blood flow could be calculated using the Fick principle. After a 20% blood loss, the PsqO2 measured during breathing of room air fell to 20% of baseline, corresponding to an 80% fall in sc blood flow; it remained low until the shed blood was returned despite compensatory changes in cardiac output. Rapid infusion of electrolyte solutions in normovolemic animals produced a temporary increase in local blood flow. Subcutaneous oximetry seems capable of quantifying peripheral perfusion and may be clinically useful.

Oxygen tension regulates the expression of angiogenesis factor by macrophages.

When cultured in a hypoxic environment similar to that found in the center of a wound, macrophages secreted active angiogenesis factor into the medium. Under conditions similar to those of well-oxygenated tissue, macrophages did not secrete active angiogenesis factor. Macrophages that secreted the factor at hypoxic conditions stopped secreting it when returned to room air. Thus the control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.