Nicholas A. Shorter

Occult spinal dysraphism in patients with anal agenesis

Recent reports have suggested an association between congenital anorectal anomalies and occult spinal dysraphism. Eighty-seven patients with anal agenesis have been treated at this institution over the last 14 years. Two of these patients had spinal cord anomalies recognized at birth (a myelomeningocele and a tethered spinal cord). Two additional patients presented with progressive neurologic deficits in early childhood and were each found to have a tethered spinal cord. To further assess the magnitude of this problem, we have used magnetic resonance imaging (MRI) of the spine to survey prospectively 23 infants with anal agenesis. Twenty-one former patients who were asymptomatic were recalled and also studied. Four of 44 patients (9%) were found to have significant occult spinal dysraphism; each child had undergone neurosurgical operation without morbidity. MRI found each child to have a tethered spinal cord, either as an isolated lesion (2) or in association with a syrinx (1) or lipomyelomeningocele (1). One of these patients had a neurologic deficit detected on careful preoperative evaluation. The other three, two of whom were less than 2 years old, had no detectable deficit. Neither the extent of the anorectal malformation, the absence of associated congenital anomalies, nor the demonstration of normal vertebral anatomy on plain radiographs of the spine precluded the presence of occult spinal dysraphism. Therefore, we recommend that all patients with anorectal anomalies undergo MRI imaging of their spines during initial evaluation to screen for occult spinal dysraphism. In addition, consideration should be given to recalling older patients for MRI evaluation.

Primary neonatal cricopharyngeal achalasia: A case report and Review of the literature

Primary cricopharyngeal achalasia is a rare cause of dysphagia in the pediatric population. In a review of the literature, only 11 well-documented cases were discovered. We report the case of a newborn with cricopharyngeal achalasia who was successfully treated with a myotomy of the upper esophageal sphincter. A review of the literature is presented and treatment options are discussed.

Autoregulation of Neuroblastoma Growth by Vasoactive Intestinal Peptide

Elevated serum levels of vasoactive intestinal peptide (VIP) are associated with some cases of neuroblastoma and correlate with a favorable prognosis. VIP has previously been shown in our laboratory to cause the in vitro growth inhibition and morphological differentiation of the human neuroblastoma cell line, LA-N-5. It is now shown that LA-N-5 cells express immunoreactive VIP and bear specific VIP receptors. Antagonism of endogenous VIP, either by competitive inhibition or receptor blockade, increased cell proliferation, suggesting that VIP is operative in normal growth regulation. Intracellular and extracellular levels of VIP were also shown to increase significantly during the retinoic acid-induced differentiation of these cells. Furthermore, a concomitant marked increase in VIP receptor expression was demonstrated with cellular differentiation. These receptors remain functional as evidenced by a matching increase in the level of detectable cAMP generated in response to exogenous VIP. It is concluded that VIP is a normal autoregulator of neuroblastoma cell growth and differentiation, and that retinoic acid-mediated differentiation may be, in part, due to endogenous VIP.

Pyriform sinus cyst and fistula in the newborn: The value of endoscopic cannulation

A case of pyriform sinus cyst and fistula presenting in the neonatal period is described. Endoscopic cannulation of the fistula tract was used to confirm the diagnosis and to simplify the resection.

Retinoic acid-induced regulation of neuropeptide Y receptor expression and function in the neuroepithelioma line SK-N-MC

UNLABELLED Neuropeptide Y (NPY) acts through specific receptors to inhibit adenyl cyclase and may have a role in neuroblastomas and neuroepitheliomas (NE) as a regulator of cell growth and differentiation. The authors have examined the status of NPY receptors in the NE cell line SK-N-MC and the effect of retinoic acid (RA), a known differentiating agent, on their expression and function. METHODS Competitive NPY binding studies were performed on normal and RA-treated cells, followed by Scatchard analysis. NPY receptor function in the absence of or following RA treatment was determined by the ability of various concentrations of NPY to attenuate the forskolin-stimulated accumulation of intracellular cAMP. The mitogenic effect of NPY was evaluated by growing normal or RA-treated cell in the presence of various concentrations of NPY. RESULTS Scatchard analysis showed a Kd of 2.3 nmol/L and a Bmax of 91,000 receptors per cell for untreated cells. RA treatment decreased receptor expression to 11,700 per cell without a significant change in receptor affinity (3.6 nmol/L). The effect of forskolin was inhibited by NPY in a dose-dependent fashion in both untreated and treated cells indicating functional receptors in both NPY stimulates the growth of normal SK-N-MC cells. NPY stimulated growth was significantly attenuated after RA treatment, possibly as a result of decreased NPY receptor expression. CONCLUSIONS Treatment of SK-N-MC cells with RA, a known differentiating agent, leads to decreased expression of functional NPY receptors and a concomitant decrease in the mitogenic effect of NPY. This supports the role for NPY in the pathogenesis of NE.