Evidence for prenatal competition among the central arbors of trigeminal primary afferent neurons: single axon analysis.

Previous studies from this laboratory have demonstrated that prenatal damage to vibrissae follicles results in significant increases in the brainstem representations of the remaining vibrissae as demonstrated by staining for the mitochondrial enzyme cytochrome oxidase (CO). Because CO is primarily a postsynaptic marker, these results do not directly address the question of whether there were changes in the projections of primary afferent fibers. To address this issue, we made intra-axonal recordings from individual vibrissa-related primary afferents in rats that sustained damage to vibrissae follicles on embryonic day 17, and then injected horseradish peroxidase (HRP) into these axons to visualize their terminal arbors in the brainstem at the level of trigeminal subnucleus interpolaris (SpI). All vibrissae-related primary afferents responded to deflection of one and only one vibrissa, and the terminal arbors of axons (N = 47) recovered from animals that sustained fetal peripheral lesions were significantly larger than those (N = 23) from normal rats. Fibers from fetally damaged animals had increased total fiber lengths and numbers of branch points. These results indicate that reduced competition among primary afferent axons results in increases in the terminal arbors that remain. These increases occur without any significant alteration in their peripheral receptive fields.

Normal development and effects of deafferentation on the morphology of superior collicular neurons projecting to the lateral posterior nucleus in hamster.

Visually responsive neurons in the superficial layers of the hamster's superior colliculus (SC) can be divided into distinct morphological and functional classes. In the preceding paper (Mooney et al., '91), we showed that neonatal enucleation has only slight and insignificant effects upon the structural characteristics of cells within a given class, but results in a significant reduction of neurons (narrow and widefield vertical cells) with dorsally directed dendritic arbors. In an effort to determine whether this change reflected differential transneuronal degeneration of these cell types or alterations in the dendritic arbors of surviving cells, this study re-examined this issue by restricting the analysis to a specific and relatively homogeneous subpopulation of superficial layer neurons, those that project to the lateral posterior nucleus (LP). Physiological recordings demonstrated that most (64.7%) tecto-LP cells in neonatally enucleated hamsters develop somatosensory receptive fields. The combination of retrograde tracing and injection of cells with Lucifer yellow in a fixed slice preparation demonstrated that nearly 75% of tecto-LP cells in normal adult hamsters are widefield vertical cells while less than 25% of the neurons filled in neonatally enucleated adults are in this class. Most of the tecto-LP cells in the neonatally enucleated adult hamsters were either horizontal cells (19.5%), giant stellate cells (24.6%), or had dendrites that were directed only toward the deep SC laminae (10.3%). Differential enucleation-induced cell death could not account for all of these changes. Tecto-LP neurons were retrogradely labelled with the carbocyanine dye, Di-I, in hamsters on postnatal day (P-) 0 (the day of birth) through P-10. As early as P-0, most retrogradely labelled neurons could be identified as either widefield (44.6%) or narrowfield (18.9%) vertical cells. These results, when considered together with those from the normal adult and neonatally enucleated adult hamsters, support the conclusion that neonatal eye removal results in a reorganizaton of the dendritic arbors of some collicular neurons that have already undergone considerable development at the time of the lesion.

Correlations between the receptive field properties and morphology of neurons in the deep layers of the hamster's superior colliculus.

Extracellular and intracellular recording, receptive field mapping, and intracellular HRP injection techniques were used to define the morphological classes of cells in the deep laminae of the hamster's superior colliculus and to determine whether there are any correlations between the structural and functional characteristics of these neurons. A total of 110 neurons were characterized and reconstructed. Of these, 23.6% (N = 26) were visual, 60% (N = 66) were somatosensory, 0.9% (N = 1) were bimodal (visual-somatosensory), and 15.4% (N = 17) were unresponsive. Of the somatosensory neurons, 72.7% (N = 48) were low threshold, 4.5% (N = 3) had a wide dynamic range, 9.1% (N = 6) responded only to noxious stimulation, and 13.6% (N = 9) had complex somatosensory receptive fields. Deep layer cells were divided into eight morphological classes. These classes were multipolar cells (26.4%, N = 29), bipolar cells (9.1%, N = 10), widefield vertical cells (7.3%, N = 8), horizontal cells (13.6%, N = 15), stellate cells (10.9%, N = 12), ventrally directed cells (5.5%, N = 6), sparse radial cells (17.3%, N = 19), and small sparse radial cells (6.4%, N = 7). Four cells (3.6%) did not fit into this classification scheme. Univariate and multivariate analyses of variance of properties such as soma area, number of branch points, total dendritic length, and volume and orientation of dendritic arbor indicated that these classes were significantly different. However, chi 2 analysis and multivariate analysis of variance indicated no significant relationships between morphological class and either laminar location or receptive field type. There was a significant positive relationship between the possession of dendrites that extended into the superficial laminae and visual responsivity.

Structural and functional consequences of neonatal deafferentation in the superficial layers of the hamster's superior colliculus.

Intracellular recording and horseradish peroxidase (HRP) injection techniques were used to evaluate the effects of neonatal enucleation upon the structural and functional properties of cells in the superficial retinorecipient laminae of the hamster's superior colliculus (SC). The physiological recordings confirmed previous results that normally visual superficial layer neurons develop somatosensory receptive fields in the enucleated animals. This study further showed that all of the physiological subclasses of somatosensory neurons normally encountered in the deep layers were present in the superficial laminae. With the exception of marginal cells, all of the morphological classes of neurons in the superficial SC laminae of sighted hamsters (narrowfield vertical cells, widefield vertical cells, stellate cells, horizontal cells, and giant stellate cells) were recovered from the blinded animals. Quantitative comparison of neurons within a given morphological class demonstrated only slight differences between cells from blind and sighted hamsters. However, there was a significant reduction in the percentage of neurons with dorsally directed dendrites in the neonatally enucleated animals. Additional experiments with the Golgi technique also demonstrated that neonatal enucleation altered the distribution of morphological cell types in the superficial SC laminae. These results suggest that enucleation in the hamster may result in relative reductions in specific cell types in the superficial SC laminae rather than dendritic changes in all of the cell classes present in these layers.

Measurement of atrial septal defect during cardiac catheterization. Experimental and clinical results.

The size of experimental and clinical secundum atrial septal defects may be accurately measured during cardiac catheterization. The position of the defects in the septum and their distance from the aortic and mitral valves may also be ascertained. A balloon catheter inflated with radiopaque dye is used for the measurement. The volume of dye in the balloon has been correlated with its maximal diameter. Thus, a no. 8-10 French catheter filled with 10 ml of diatrizoate (50 percent) has a diameter of approximately 25 mm and a no. 8-22 French catheter filled with 40 ml of diatrizoate a diameter of approximately 43 mm. Persistent arrhythmias or other adverse effects of the procedure were not observed. There was a high correlation between balloon-measured atrial septal defects and those measured at necropsy in the animals or at operation in the patients. These measurements aid in determining whether an ostium secundum defect is of proper size and location to be closed transvenously and may also prove valuable in physiologic studies of atrial septal defects or other cardiac anomalies.

Nonoperative closure of left-to-right shunts.

Efforts to close left-to-right shunts at Ochsner Medical Institutions have been directed toward atrial septal defects (ASD) and patent ductus arteriosus (PDA). PDA's were constructed in dogs by interposing a segment of jugular vein between the aorta and main pulmonary artery. Five dogs in which the PDA was closed by a plug device inserted through the femoral vessels were put to death at 6 to 12 months. Histologic sections showed good fibrous ingrowth with endothelial covering on the aorta and pulmonary artery sides. There were no migrations redidual shunts. At cardiac catherterization, 18 patients had ASD's sized and located as to position in the septum. The sized ranged from 13 to greater than 30 mm. in diameter. The ASD sizes in patients who underwent standard operative closure were compared to the measurements at catheterization, and the variation was insignificant. In 5 patients, centrally positioned secundum ASD's were closed with double umbrella devices, 25 to 35 mm. in diameter. Anatomic contraindications for umbrella closure include ASD's greater than 30mm. in diameter, anomalous pulmonary venous connection, common atrium, inferiorly or superioly located secrumdum ASD, and sinus venosus ASD. Follow-up studies from 6 to 12 months on 5 patients with umbrella closure have revealed no hemolysis, arrhythmias, thromboembolism, migration, or other untoward effects.

Correction of Type C complete atrioventricular canal. Surgical considerations.

Case histories of 8 consecutive patients who underwent surgical correction of Type C complete atrioventricular (A-V) canal at the Ochsner Medical Center over the past 2 years were analyzed. Ages ranged from 1 1/3 to 14 years. Before bypass, the level to which the common leaflets ascend and the arc that they inscribe are determined by palpation to ensure their proper reconstitution on the canal patch. The major area of closure is usually allocated to the ventricular portion. Mapping the conduction system and tying sutures with the heart beating in high-risk conduction areas prevent heart block. Precise marking and splitting of the valve leaflets and reattachment with interrupted felt-buttressed sutures avoid disruption. All patients survived the operation and have shown clinical improvement. At recatheterization, 7 of 8 patients have shown a definite decrease in mitral insufficiency. Right ventricular pressures returned toward normal and there were no significant residual shunts. Associated anomalies or previous operations have not been a contraindication, and since we have begun using the present technique, we have achieved consistently good results without prosthetic valves.

Caspase-3 activation induced by inhibition of mitochondrial complex I is facilitated by glycogen synthase kinase-3beta and attenuated by lithium.

The compound 1-methyl-4-phenylpyridinium (MPP) is a selective inhibitor of mitochondrial complex I, and is widely used in model systems to elicit neurochemical alterations that may be associated with Parkinson's disease. In the present study treatment of human neuroblastoma SH-SY5Y cells with MPP resulted in a time- and concentration-dependent activation of the apoptosis-associated cysteine protease caspase-3, and caused morphological changes characteristic of apoptosis. To test if the activation state of the cell survival-promoting phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway affects MPP-induced caspase-3 activation, PI3K was inhibited with LY294002, or activated with insulin-like growth factor-1. MPP-induced caspase-3 activation was increased by inhibition of PI3K, and decreased by stimulation of PI3K, indicative of anti-apoptotic signaling by the PI3K/Akt pathway. To test if glycogen synthase kinase-3beta (GSK3beta), a pro-apoptotic kinase that is inhibited by Akt, is involved in regulating MPP-induced apoptosis, overexpression of GSK3beta and lithium, a selective inhibitor of GSK3beta, were used to directly alter GSK3beta activity. MPP-induced caspase-3 activity was increased by overexpression of GSK3beta. Conversely, the GSK3beta inhibitor lithium attenuated MPP-induced caspase-3 activation. To test if these regulatory interactions applied to other mitochondrial complex I inhibitors, cells were treated with rotenone. Rotenone-induced activation of caspase-3 was enhanced by inhibition of PI3K or increased GSK3beta activity, and was attenuated by inhibiting GSK3beta with lithium. Overall, these results indicate that inhibition of GSK3beta provides protection against the toxic effects of agents, such as MPP and rotenone, that impair mitochondrial function.

Tectospinal neurons in hamster contain glutamate-like immunoreactivity.

Immunocytochemistry with a monoclonal antibody directed against glutamate revealed numerous immunoreactive cells in the hamster's superior colliculus (SC). A large number of these neurons were located in the deep layers and many were in the stratum album intermedium (SAI). These neurons appeared similar to the large multipolar cells that have been shown to project to the cervical spinal cord in this species. The combination of retrograde tracing using either Fluoro-Gold- or FITC-labelled latex beads with immunocytochemistry for glutamate revealed that many of the immunoreactive cells did, in fact, project into the predorsal bundle and extend axons as far as the cervical spinal cord.

Surgical correction of complete tracheoesophageal cleft.

Laryngotracheal esophageal cleft is a rare congenital anomaly that should be considered in the differential diagnosis of any neonatal respiratory distress aggravated by feeding. Diagnosis is difficult and repeat endoscopic examinations may be necessary. In complete clefts, immediate surgical repair is indicated with combined approach through the chest and neck and incorporation of part of the esophageal wall into the repair. Because the cleft may be associated with esophageal atresia and/or tracheal esophageal fistula, it should be suspected in patients who have persistent symptoms after successful repair.

The role of embolization therapy in the treatment of congenital heart disease.

Embolization therapy plays a significant role in the treatment and palliation of congenital heart disease. Currently, there are several devices available to occlude these superfluous vascular connections. This article reviews the indications, results and the current technology available for transcatheter embolization of vessels.

Transcatheter closure of patent ductus arteriosus with the Amplatzer duct occluder: short-term follow-up.

BACKGROUND: Transcatheter closure of the patent ductus arteriosus is a well established procedure. The objective of this study was to assess the effectiveness and the safety of the Amplatzer duct occluder. METHODS AND RESULTS: Occlusion of the patent ductus arteriosus was attempted in 23 patients. The median weight was 11.7 Kg (range, 5 kg - 42.4 kg) with a mean ductus diameter of 3.7 mm (range, 1.6 - 7.2 mm). The immediate closure rate was 86% with a closure rate of 100% at 6 months, 1 year and 2 years following device placement. There was one device embolization that occurred immediately following device placement. No patient had aortic narrowing or pulmonary artery stenosis following the procedure. CONCLUSIONS: The Amplatzer duct occluder is safe and effective in the closure of a patent ductus arteriosus up to 7.2 mm in diameter. Selecting a device at least 12 mm larger than the minimal ductal diameter can minimize embolization.

Lymphoma with large intracavitary metastasis to the heart. Report of a case.

A case if reported of a 2 1/2-year-old boy with an extensive filtration of the retroperitoneum, mediastinum, and almost every organ of the body with a very primitive type of tumor identified as a poorly-differentiated mixed histiocyticlymphocytic lymphoma. The right atrium was completely filled with a large intracavitary metastasis which caused obstruction of the venous return to the heart with subsequent death.

Double mitral valve. Report of a case and review of the literature.

A case of double mitral valve orifice associated with atrioventricular canal was found at operation. These two anomalies are frequently associated. Double mitral valve is usually subclinical and does not necessarily need to be corrected, depending on the associated anomalies, the extent of the defect, and the personal experience of the surgeon. The embryology of double mitral valve is complicated and still needs to be clarified.

Estrogen-androgen for hormone replacement. A review.

OBJECTIVE: To critically examine the role of androgens as part of postmenopausal hormone replacement therapy. STUDY DESIGN: Examination of original reports and reviews obtained by electronic database searches and supplemented by manual search of bibliographies. RESULTS: As compared to estrogens alone, estrogen-androgen therapy may better protect against osteoporosis and increase libido, energy levels and general sense of well-being. However, estrogen-androgen replacement also reduces the beneficial increases in high-density lipoprotein induced by estrogens alone, although this effect may be offset at least partially by decreases in atherogenic triglycerides. The long-term net effect of estrogen-androgen replacement on cardiovascular disease remains unknown. CONCLUSION: Although the literature includes relatively few clinical trials or well-controlled studies and is further limited by the subjective nature of outcomes, such as sexual and psychological function, the available data suggest that for many postmenopausal women, estrogen-androgen replacement may provide benefits beyond those provided by estrogen-only replacement therapy.