For this new Catalyst feature, we have asked NIH scientists to give us the latest news from recent meetings. We welcome your comments and contributions.
The American Academy of Neurology met May 6-13 in Seattle. Every year, several of the abstracts submitted before the meeting are selected as "Works in Progress for Expedited Presentation." There were three this year. Howard Weiner and colleagues from the Brigham and Women's Hospital in Boston reported on correlations of magnetic resonance imaging (MRI) with immune and clinical measures in multiple sclerosis (MS) patients followed closely over one year. They found that measures from the MRI scans such as lesion volume and number of lesions correlated well with clinical scores. There were also correlations with some immune measures, the best being with increased numbers of interleukin-2 receptor-bearing T cells. Other presentations supported the growing consensus that MRI is an excellent way to monitor MS patients.
Meanwhile, Stella Papa and colleagues from NINDS showed that an N-methyl-D-aspartate (NMDA) receptor antagonist could suppress levodopa-induced dyskinesias in monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Investigators of the basic pharmacology of Parkinson's disease have become interested in the possible role of glutamatergic innervation of the basal ganglia. In this study, a competitive NMDA antagonist was given to Parkinsonian monkeys that had dyskinesias produced by overtreatment with levodopa. The NMDA antagonist relieved the dyskinesias with minimal negative influence on motor function. This suggests that it may be possible to treat clinical dyskinesias while maintaining levodopa's beneficial effects on Parkinsonian symptoms. The third abstract was from NCI's Bertrand Liang, who reported on gene amplification in human gliomas. He identified a novel cDNA with a high degree of amplification in gliomas of diverse grades--indicating that this gene may be important in the pathogenesis of gliomas.
As for clinical trials, there were many reports of drug therapies for various neurological diseases, but nonpharmacological methods were also abundant. Enthusiasm continued for surgical approaches to the treatment of Parkinson's disease, particularly pallidotomy, which was reviewed in a special session featuring Mahlon DeLong of Emory University in Atlanta, Anthony Lang of the University of Toronto, and Enrico Fazzini of New York University School of Medicine. Deep-brain stimulation of the ventral intermediate (VIM) nucleus of the thalamus was reported to be useful for severe tremors. In addition, Alvaro Pascual-Leone, formerly of NINDS and now of the University of Valencia in Spain, presented data indicating that repetitive stimulation of the motor cortex with noninvasive transcranial magnetic stimulation (TMS) may have value in treating the slowness of patients with Parkinson's disease. In other work involving TMS, Pascual-Leone's team and another group led by Mark George of NIMH both showed that repetitive TMS of the left frontal lobe had some effect in improving symptoms in patients with depression.
-- Mark Hallett , NINDS
American Thoracic Society
The American Thoracic Society/American Lung Association International Conference, was held May 20-24 in Seattle. On the clinical side, there was considerable interest in barotrauma from mechanical ventilation. The recurring theme was that alveolar overdistension may cause or worsen diffuse lung injury, impair gas exchange, and increase the work of breathing. The take-home message was that total ventilation can be minimized by keeping both respiratory rate and tidal volume low and by keeping inspiratory flow rates high, even at the expense of high peak inspiratory pressure. Meeting organizers added a mini-symposium on another hot clinical area--volume-reduction surgery for treatment of chronic obstructive pulmonary disease (COPD). The procedure, dubbed the "pulmonary CABG [coronary artery bypass graft] of the `90s," improves ventilation through ablation of severely emphysematous areas of the lung. Unresolved issues include patient-selection criteria and optimal surgical technique.
The genetics of pulmonary disease, particularly asthma, also received increased attention. High immunoglobulin E (IgE) levels correlate with bronchial hyperresponsiveness and allergic asthma. Several genes on chromosome 5q, including some that encode interleukins, may be involved in the regulation of IgE and the development or progression of airway inflammation and, intriguingly, with bronchial hyperresponsiveness. Other studies indicate that airway reactivity and the susceptibility to different types of asthma may be correlated with the ß2-adrenergic receptor isoform. ß2-adrenergic-receptors containing glycine-16 were found more frequently in patients with nocturnal asthma than in those with nonnocturnal asthma; airway reactivity was less in patients with the glutamate-27 isoform. As might be predicted from the clinical findings, lab studies found that the glycine-16 isoform was associated with increased agonist-mediated receptor downregulation and the glutamate-27 isoform with less. Asthma may also be an important component in hereditary lung diseases. In studies of a1-antitrypsin deficiency, an inherited disease associated with an increased risk of emphysema and/or cirrhosis, the NHLBI-sponsored registry reported that among patients with a1-antitrypsin deficiency and emphysema, those with reactive airway disease showed a more rapid decline in lung function.
--Norton Elson, Shan C. Chu, Mark L. Brantly,
N. Gerard McElvaney,
N. Tony Eissa ,
American Academy of Allergy, Asthma,
Asthma was also a major focus of the 1995 International Meeting of the American Academy of Allergy, Asthma and Immunology, held in New York City Feb. 24-28. Several epidemiological studies examined the recent rise in asthma deaths, particularly in urban areas. Evalyn Grant of Rush-Presbyterian-St. Luke's Medical Center presented evidence that asthma is underdiagnosed in the inner city of Chicago. Similarly, Ned Rupp of the Medical College of Georgia in Augusta documented the underdiagnosis of allergy in Latino inner city Philadelphia.
Progress was also reported in identifying genes that may be responsible for the atopic state. Pamela Amelung of the University of Maryland School of Medicine in Baltimore reported that a major gene regulating IgE maps to 5q. For several years, it has been known that there is an IgE-specific and IgE-dependent factor in serum and secretions that induces histamine release from basophils sensitized with IgE from certain donors. Susan McDonald of Johns Hopkins Medical Institutions in Baltimore reported the cloning of this molecule, referred to as histamine-releasing factor (HRF). Studies are now under way to characterize HRF's biologic activity and its mechanisms of action. Apoptosis of inflammatory cells including eosinophils may provide one way of controlling inflammation. Tetsuya Adachi of Kihara Hospital in Tokyo reported that corticosteroids and macrolides induce apoptosis in eosinophils stimulated with interleukin-5.
Taken as a whole, the developments discussed at the AAAAI meeting demonstrate how rapidly basic biology advances are being applied to the understanding of the pathogenesis of inflammatory diseases and to the treatment of allergic disorders.
--Dean Metcalfe, NIAID