Comparative effects of oral and inhaled verapamil on antigen-induced bronchoconstriction

We investigated the comparative effects of oral and inhaled verapamil on specific airway conductance (SGaw) and allergic bronchial reactivity. Ten asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma were studied on four different days, without and with pre-treatments by oral (160 mg) or inhaled (20 mg) verapamil. Bronchial reactivity was measured as the cumulative provocative dose of ragweed antigen which caused a 35 percent decrease in SGaw, ie PD35. The amount of inhaled verapamil actually deposited in the tracheobronchial tree was estimated to be 0.56 mg. Mean SGaw was not affected by either mode of administration; mean SGaw (SE) was 0.13(.02) and 0.12(.02) L/sec-1 before and .14(.02) and 0.12(.02) L/sec-1 after oral and inhaled verapamil, respectively. Mean (SE) PD35 was reproducible on two control days, ie 0.9(.4) and 0.8(.4) breath units, respectively. Inhaled verapamil increased mean PD35 to 18.8 (10.8) breath units (p less than 0.02), while oral verapamil had no significant effect on mean PD35. This study demonstrates that route of administration of calcium antagonist verapamil is an important factor in protection against antigen-induced bronchoconstriction. Inhalation of verapamil appears to be more effective than oral administration.     

Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies

Human erythroid malignancies (polycythemia vera [PV] and erythroleukemia) are associated with erythropoietin (Epo)-independent growth and differentiation. Missense or nonsense mutations in the Epo receptor (Epo-R) have been recently described in experimental erythroleukemia in mice and in cases of erythrocytosis in humans. To search for a similar genetic alteration in erythroleukemia and PV, we entirely sequenced the exons of the Epo-R gene as well as the intron- exon junctions in these disorders using polymerase chain reaction. In 1 of 10 cases of erythroleukemia, a single allele mutation was found in the 8th Epo-R gene exon that changed asparagine 487 into a serine. No Epo-r gene mutation was found in 12 PV cases studied, but the same mutation (N487S) was found in 1 patient with polycythemia that did not fulfill the criteria of PV (polycythemia of unknown origin). We did not detect this mutation after sequencing part of the 8th exon of the Epo-R gene from 21 other patients with polycythemia of unknown origin and 51 normal controls. The Epo-R mutation was also found in Epstein-Barr virus-derived cell lines from both cases, suggesting that it is not related to the malignant clone. Therefore, this mutation does not appear to be somatic, although no familial cases were found. The biologic effect of this mutation was subsequently studied. Erythroid progenitors from the polycythemic patient normally responded to Epo, whereas those from the erythroleukemic patient were Epo-independent due to autocrine stimulation by Epo. The normal and the mutated Epo-R were transfected into the murine Ba/F3 cell line. Both types of cells displayed the same response to Epo for proliferation, differentiation, and inhibition of apoptosis. Although this mutation may destroy a consensus binding site for Grb2, no obvious differences either in the pattern of Epo-induced tyrosine phosphorylated proteins or in the binding of Grb2 to the Epo-R were observed. In conclusion, a somatic Epo-R missense mutation does not appear to be a molecular mechanism involved in the abnormal growth of human erythroleukemia and PV. However, the Epo-R mutation (N487S) that we describe is located in the same tyrosine sequence beginning at AA 485 as the one previously observed (P488S) in as case of polycythemia (Sokol et al, Exp Hematol 22:447, 1994). These results suggest that this phosphopeptide sequence may play an important role in Epo signalling.     

Short-term effect of albuterol, delivered via a new auxiliary device, in wheezy infants.

In a double-blind, placebo-controlled study, the response of lung function to albuterol, topically administered by a metered-dose inhaler (MD) through a baby-adapted auxiliary device, was evaluated in 36 wheezy infants (1.6 to 25.2 months of age; median 8.1 months). The auxiliary device contains an air chamber of 350 ml and two low-resistant valves separating the inspiratory from the expiratory line. After baseline lung function measurements by infant whole-body plethysmography, the patients were randomly assigned to inhale either three times two puffs albuterol (100 micrograms/puff) or three times two puffs placebo at 5-min intervals. Changes in the degree of pulmonary hyperinflation, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by airway conductance (Gaw), were measured at 5-min intervals for up to 30 min. TGV and Gaw were expressed as standard deviation scores (SDS) of values predicted, and patients improving TGV and/or Gaw more than 2 SD were considered responders. In comparison with placebo, a significant percentage improvement in TGV (by the mean 26 to 53%) and a significant percentage improvement in Gaw (by the mean 34 to 51%) could be found in the active treatment groups. The study documents the usefulness of a new auxiliary device for the administration of aerosolized bronchodilators to wheezy infants.     

Enhancing trauma education worldwide through telemedicine

Advances in information and communication technologies are changing the delivery of trauma care and education. Telemedicine is a tool that can be used to deliver expert trauma care and education anywhere in the world. Trauma is a rapidly-evolving field requiring access to readily available sources of information. Through videoconferencing, physicians can participate in continuing education activities such as Grand Rounds, seminars, conferences and journal clubs. Exemplary programs have shown promising outcomes of teleconferences such as enhanced learning, professional collaborations, and networking. This review introduces the concept of telemedicine for trauma education, and highlights efforts of programs that are utilizing telemedicine to unite institutions across the world.