The complex enterprise of modelling prenatal exposure to cigarettes: what is ‘enough’?

While there is a burgeoning body of research linking smoking during pregnancy to problem behaviour in offspring, a major criticism of this work has been the crude measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, we used a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modelling techniques. In this paper we report on the analytical approaches we have developed, including patterns of exposure over time and best-estimate approaches that combine self-report and cotinine measures, and compare their predictive value in relation to different dimensions of fetal growth as a first step towards examining the utility of greater precision of exposure measurement.
Surprisingly, in this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterisation in developmental studies.     

Brief report: Does fenfluramine treatment enhance the cognitive and communicative functioning of autistic children?

This project was supported by two separate research grants from the Trust Fund Board, Washington Association for Retarded Citizens to Richard Neel and Truman E. Coggins. The research was also supported by a training grant to the University of Washington entitled Comprehensive Training in Mental Retardation and Other Handicapping Conditions (MCH-000913, Clifford J. Sells, M.D., Principal investigator); and, a training grant to the University of Arizona entitled Doctoral and Post-Doctoral Leadership Training and Clinical Research, Teaching and Administration: Clinical Language Research Center (G008630088, Linda Swisher, Ph.D., principal investigator). We are indeed grateful to the parents of our five subjects for their patience, understanding, and commitment. Finally, we express our appreciation to Arelene Chaussee for her technical expertise and untiring spirit.     

Importance of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration

Paraneoplastic neurologic syndromes are disorders of the nervous system function caused by cancer but not due to metastatic disease, vascular or metabolic deficits, infections, nutritive deficiency, nor side effects of antineoplastic drugs or irradiation. Immunologic factors probably play the crucial role in the pathogenesis of paraneoplastic neurologic syndromes, but nonimmunologic mechanisms that include metabolic abnormalities and competition for substrate are also involved. Paraneoplastic cerebellar degeneration most commonly occurs in the setting of gynecologic cancers, but it accompanies the small-cell lung cancer too. Other tumors are infrequently associated with cerebellar degeneration. Several paraneoplastic antibodies have been identified in patients with paraneoplastic cerebellar degeneration. Their association with particular cancers may help identify an occult lesion. Anti-Yo antibodies are directed against Purkinje cell antigens and occur in patients with cerebellar degeneration who have breast cancer or gynecologic tumors. A target antigen of anti-Yo antibody is CDR2 protein that is normally expressed only in the brain and testis. Patients with paraneoplastic cerebellar degeneration present with dizziness, nausea and vomiting followed by gait instability, diplopia, gait and appendicular ataxia, dysarthria and dysphagia. Therapeutic options include tumor excision, chemotherapy and/or irradiation, and adjuvant therapy with glucocorticoids, immunoglobulins and plasmapheresis. The role of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration is still uncertain. Reports of its efficacy are anecdotal. We present patient with paraneoplastic cerebellar degeneration with positive anti-Yo antibodies and tumor of the ovaries whose neurologic status significantly improved after four daily plasmaphereses, which was accompanied by a fourfold decrease in the anti-Yo antibodies titer. Further investigations are needed to define a protocol for plasmapheresis in the treatment of patients with paraneoplastic syndromes.     

Ontogeny of guanylin-immunoreactive cells in rat salivary glands

Guanylin-like peptides regulate electrolyte/water transport through the epithelia. Moreover, these peptides possess antiproliferative activity and regulate the turnover of epithelial cells. In an earlier study we localized guanylin immunoreactivity in secretory ducts of adult rodent salivary glands. In this study we investigated the appearance and distribution pattern of this peptide during the development of rat salivary glands. Guanylin immunoreactivity appeared at the beginning of cell differentiation from solid bud, on embryonic day 17 in the submandibular and sublingual glands and after day 18 in the parotid gland. Guanylin immunoreactivity appeared first in ductal and acinar anlage: its cell distribution pattern and fate differed in these two compartments. In the duct cells guanylin immunoreactivity spread after the duct system developed, whereas in acinar cells it disappeared after cell differentiation. The guanylin immunoreactivity we detected in adult salivary duct cells accords with guanylins role in regulating electrolyte and water transport through the various epithelia. It does so by activating guanylate cyclase-C receptor, increasing intracellular cGMP concentration, and phosphorylating the cystic fibrosis transmembrane conductance regulator (CFTR) protein by the cGMP-dependent protein kinase II. This signaling cascade couples to the ductal electrolyte/water secretion and modulates finally the electrolyte composition of the saliva. On the other hand, CFTR is also involved in mechanisms of cell growth, by regulating apoptosis, and promoting cell differentiation. The early diffuse guanylin immunoreactivity we observed in ducts and acinar anlage, before the secretory set is operative, suggests guanylin has a role in cell differentiation.     

Ontogeny of galanin-immunoreactive elements in chicken embryo autonomic nervous system

To elucidate the main ontogenetic steps of galanin immunoreactivity within the extrinsic nerve supply of the alimentary tract, we undertook an immunohistochemical study of chicken embryo specimens. Fluorescence and streptavidin-biotin-peroxidase protocols were combined, using a galanin polyclonal antiserum, on transverse serial sections obtained from chicken embryos from embryonic Day 3 (E3) to hatching, and from 9-day-old newborn chicks. Galanin-immunoreactive cells were first detected at E3.5 within the pharyngeal pouch region, the nodose ganglion, the primary sympathetic chain, primitive splanchnic branches and the caudal portion of the Remak ganglion. At E5.5 galanin-immunoreactive cells and fibers appeared in the secondary (paravertebral) sympathetic chain, splanchnic nerves, peri- and preaortic plexuses, adrenal gland anlage and visceral nerves. Galanin-immunoreactive cells also lay scattered along the vagus nerve, and in the intermediate zone of the thoracolumbar spinal cord. At E18, galanin-immunoreactive cells and fibers were found along the entire Remak ganglion and around the gastrointestinal blood vessels. In post-hatching-9-day old chicks, the para- and prevertebral ganglia, but not the intermediate zone of the spinal cord, contained galanin-immunoreactive cells. Data indicate the presence of a consistent "galaninergic" nerve system supplying the chick embryonal gut wall. Whether this system has growth or differentiating role remains to be demonstrated. Its presence and distribution pattern in the later stages clearly support its well known role as a visceral neuromodulator of gut function.     

Bone Graft Alternatives for Spinal Fusion

Bone grafting to achieve fusion is frequently performed in spinal surgery. Autograft is the gold standard bone graft material. However, due to limitations of supply and morbidity associated with the harvest of autograft, alternatives are being considered. Osteoconductive matrices, such as allograft, calcium or ceramic preparations are one such class of potential bone graft alternatives, but generally they lack osteoinductive properties. Recent attention has focused on osteoinductive materials such as demineralised bone matrix, recombinant bone morphogenetic proteins and bone marrow aspirates or blood product concentrates. These products may be combined with osteoconductive carriers and are clearly finding a place in the clinical arena.     

Human pulmonary alveolar type 2 cells contain an apical membrane glycoprotein common to malignant cells

A monoclonal antibody, Ca1, raised against a detergent extract of Hep 2 cells derived from a human laryngeal carcinoma, was shown in these studies to bind to the apical surface of normal alveolar type 2 cells but not type 1 cells in the human lung. In lung specimens from patients with alveolitis, the antibody also bound to hyperplastic type 2 cells and to transition cells which were in the process of becoming alveolar type 1 cells. Ca1 binds to the apical plasma membrane and to internal membranes of cytoplasmic vesicles thought to be involved in the packaging of pulmonary surfactant. A surfactant-enriched fraction of human lung lavage did not bind the Ca1 antibody suggesting that the antigen was not an integral component of secreted surfactant. In normal human lung parenchyma, Ca1 binds only to type 2 cells, however it also binds to the apical surface of Clara cells in areas of cellular hyperplasia. Solubilized homogenates of whole lung, of a cell membrane fraction and of Hep 2 cells, immunoprecipitated with Ca2, separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and probed with iodinated lectins, revealed that terminal glycosylation of the type 2 cell antigen differed from that of Hep 2 cells. Ca1 and a 330 kilodalton type 2 cell glycoprotein bind the lectin Maclura pomifera agglutinin. These two glycoproteins represent the first defined membrane markers of the apical surface of the human type 2 cell.     

Thoracolumbar Spine Trauma: II. Principles of Management

The care of patients with thoracolumbar spine trauma with or without neurologic deficits has evolved dramatically over the past 20 years with the emergence of tertiary-care spinal injury centers and the development of more effective spinal instrumentation and anesthesia techniques. Despite these advances, the majority of patients with thoracolumbar injuries are still treated nonoperatively with cast or brace immobilization and early ambulation. More aggressive treatment is guided by the use of classification systems that detail the mechanism of injury, the degree of compromise of spinal structures, and the potential for late mechanical instability or neural injury. The goal of treatment remains attainment of spinal stability with protection or improvement of the patient's neurologic status, allowing rapid and maximal functional recovery.     

Pedicle-Screw Fixation in the Lumbar Spine

This article provides a perspective on the development of pedicle-screw fixation in the lumbar spine, the biomechanics of its application, the possible complications, and the scientific evidence that supports specific applications in selected disorders. The overall goal is to objectify the debate currently surrounding the use of these devices. Lumbar-pedicle fixation devices are currently considered class III med-ical devices. According to the Food and Drug Administration, such devices are investigational or experimental, have not been proved safe and effective, and may potentially pose a risk to patients.