Total anatomic correction of interrupted aortic arch complex. Experience in 4 infants

In two cases of interrupted aortic arch (IAA) of type A, one associated with a ventricular septal defect (VSD) and one with an aortopulmonary window, and two of type B, both associated with a VSD, total anatomic repair was performed at respective ages of 6 months and 24, 8 and 3 days. All four operations were performed through a median sternotomy, using profound hypothermia and circulatory arrest. The repair included resection of the patent ductus arteriosus, direct end-to-side anastomosis of the descending to the ascending aorta and closure of the VSD or, in one case, of the aortopulmonary window. The two oldest infants (with type A IAA) survived. Reexamination two years postoperatively demonstrated good width of the aortic anastomosis with no gradient. In the child who had had an aortopulmonary window there was a proximal tight stenosis of the right pulmonary artery, which was corrected at reoperation. Total anatomic correction of IAA through an anterior approach is technically feasible and the aortic anastomosis seems to grow satisfactorily. The management of very sick neonates with IAA remains a great challenge.     

Enhanced sprouting of retinotectal fibers after early superior colliculus lesions in hamsters treated with gangliosides

Summary The effects of exogenous gangliosides on sprouting of optic tract axons was studied in hamsters which, after a right tectal lesion on the day after birth (P1), had an abnormal retinotectal projection from the left eye to the left superior colliculus (SC). Sprouting of these axons was induced by removing the competing input by right eye removal on postnatal day 9 (P9). Intraperitoneal G_M1, given daily and started on P9, significantly stimulated the sprouting response. This was demonstrated by Fink-Heimer silver staining of anterograde axonal degeneration three days after the left eye was removed on P36. Terminal fields in the left SC were, in average, twice as large compared to controls. An estimate of the total number of terminals (silver stained particles) revealed a value of 7.9×10⁶ for G_M1 and 3.2×10⁶ for control hamsters, respectively. Diencephalic structures which also receive collateral input from the sprouting optic tract did not show any alterations in the size of the terminal field due to G_M1-treatment, suggesting that, in vivo, gangliosides fail to initiate sprouting in areas that have not previously been denervated. Unexpectedly, G_M1-treated hamsters also had significantly smaller right SC damage and less left damage near the midline. Subsequent reanalysis of the data based on a lesion-matching procedure indicates that effects on reducing atrophy were independent of the G_M1-enhanced sprouting of retinofugal axons. These findings provide the first direct evidence that exogenous G_M1 stimulates lesion-induced axon sprouting in the mammalian brain.     

Restoration of vision I: neurobiological mechanisms of restoration and plasticity after brain damage - a review

Lesions in the central nervous system often lead to loss of vision due to visual system involvement. In the course of weeks or months, some vision can recover in rats, cats, monkeys, and humans, though it is mostly incomplete. This paper reviews the current knowledge of the under-lying neurobiological mechanism of recovery of vision, particularly those observed in adult rats with partial optic nerve crush (ONC). Immediately after ONC, rats are almost completely blind, evident by their inability to perform visual tasks such as brightness and pattern discrimination and they fail to orient towards small, moving targets. Within about two weeks, however, rats significantly recover some of their lost visual functions despite the fact that only about 10 % of the retinal ganglion cells (RGCs) maintain a viable connection with their brain tar-gets. Molecular, anatomical and physiological studies have identified some of the neurobiological determinants of this visual restitution. Immediately following ONC there is a massive soma swelling of about 80 % of the RGCs with subsequent cell death due to apoptosis and necrosis. The remaining 20 % survive with or without axonal connection to their target and undergo marked changes: (i) about half of these RGCs experience a moderate, reversible soma swelling, (ii) there is a loss of anterograde axonal transport in the optic nerve which partially recovers after several weeks, and (iii) many of the surviving RGCs undergo alterations in gene expression, particularly that of the NR1 receptor and the immediate early gene, c-jun. While these changes may be part of an adaptive program of the cells to cope with the trauma, cell survival in the retina does not correlate well with subsequent recovery of vision. We have therefore also studied plasticity in the down stream denervated brain structures which are innervated by retinofugal pathways, particularly the superior colliculus. Here we found (i) recovery of metabolic activity and (ii) changes in gene expression, such as an up-regulation of the enhancer of split (R esp-1) gene. When viewed together with studies on recovery of vision and neuronal reorganization done in other laboratories it is clear that recovery of vision involves simultaneous plasticity in the damaged structure itself and, transsynaptically, in down-stream structures such as the tectum, the lateral geniculate nucleus and visual cortex. Considering both pre-clinical and clinical evidence, I propose the biological substrate underlying restoration of vision as follows: surviving neurons within areas of partial damage - which corresponds clinically to "transition zones" located between intact and deficient visual field sectors - act in concert with down-stream areas, which themselves undergo dramatic reorganization to cope with a condition of reduced, but residual input. Restitution of vision is therefore a multifactorial event of within-systems plasticity, involving neurobiological alterations along the entire retinofugal axis. It is likely that these mechanisms are also responsible for visual improvements that are seen both in animals and patients after prolonged visual restitution training.     

Enlargement of a chronic aseptic lumbar epidural abscess by intraspinal injections--a rare cause of progressive paraparesis

The frequent use of invasive procedures at the spinal cord such as epidural injections has led to an increased incidence of iatrogenic abscesses. We report the case of a patient who suffered from low back pain. During epidural lumbar injections of steroids the patient developed severe radicular symptoms, resulting in severe paraparesis. We demonstrate the rare cause of this progressive deterioration, being a combination of a preexisting chronic aseptic epidural abscess and an iatrogenic enlargement by repeated epidural injections. MR-Scans demonstrated a mass lesion at the L4/5 vertebral level, which was surgically removed. Histological evaluation revealed the presence of a chronic aseptic spinal epidural abscess with acute bleedings. Histology and MR-Data disclosed multiple deposits of the applied drug within the abscess and in the surrounding paravertebral soft tissue. The authors prove that the cause of the neurological deterioration was due to epidural injections into a preexisting lumbar chronic aseptic epidural abscess. Harmful and unpleasant complications may occur following epidural injections. Though we present a very rare cause of such complications, a careful monitoring of the neurological status of the patient is necessary as well as the early application of MR imaging in the case of deterioration.     

Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis.

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in the metabolism of fatty acids and is an important tissue biomarker in the prostate to distinguish normal glands from prostate cancer. Here, for the first time, we evaluated the expression of AMACR protein in normal breast, ductal carcinoma in situ, and invasive carcinomas. By immunofluorescence and immunohistochemistry, AMACR was seen in cytoplasmic granules consistent with a mitochondrial and peroxisomal localization. AMACR expression was determined by immunohistochemistry on 160 invasive carcinomas with long follow-up, using a high-density tissue microarray, and evaluated by two methods: standard pathology review and quantitative image analysis. AMACR was overexpressed in 42 of 160 (26%) invasive carcinomas, and it was associated with a decrease in tumor differentiation, a feature of aggressive breast cancer. Quantitative analysis allowed for better discrimination and more accurate evaluation of low-intensity staining. In conclusion, AMACR protein is expressed in normal breast and its expression seems to increase in invasive carcinomas. We observed stronger AMACR protein expression in high-grade carcinomas when compared with low-grade ones. Quantitative image analysis is a novel way to accurately and reproducibly evaluate immunohistochemistry in breast tissue samples using high-density tissue microarrays.