Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation

After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell- depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B- cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers.     

Regulation of stimulated integrin surface expression in human neutrophils by tyrosine phosphorylation

The control of the adhesive properties of human neutrophils is an essential element of their defense function. One level at which this control is exerted involves the upregulation of the surface expression of beta 2-integrins. In this study, we have examined the potential involvement of tyrosine phosphorylation in the latter process. Two inhibitors of tyrosine kinases with differing modes of action, erbstatin and herbimycin A, were found to inhibit the expression of CD11b and CD18 stimulated by chemotactic factors (fMet-Leu-Phe or leukotriene B4) or growth factors (tumor necrosis factor alpha). This inhibition was not shared by an inactive analog of erbstatin or by the protein kinase C inhibitor Ro 31-8330. Erbstatin also inhibited the unveiling of activation-specific neoepitopes detected by antibody CBRM1/5. Pretreatment of neutrophils (but not of endothelial cells) with erbstatin inhibited the stimulation of neutrophils' adherence to endothelial cells induced by fMet-Leu-Phe. Augmentation of tyrosine phosphorylation by inhibiting tyrosine phosphatases using hydroperoxyvanadate led to an increased surface expression of CD11b and CD18 and enhanced the adhesion of neutrophils to endothelial cells. Finally, the leumedin NPC 15669, which had previously been shown to inhibit stimulated CD11b expression and neutrophil adherence to endothelial cells and to exhibit anti-inflammatory properties in various in vivo models of inflammation, inhibited the stimulation of tyrosine, phosphorylation induced by fMet-Leu-Phe. Taken together, these data establish a strong correlation between tyrosine phosphorylation and integrin upregulation in stimulated human neutrophils.     

Assessing the delivery of neutrophils to tissues in neutropenia

Studies of neutrophil kinetics in neutropenic individuals, as well as clinical observations of variability in the occurrence of infection among patients with neutropenia, have suggested that blood neutrophil counts may not uniformly reflect the effective delivery of neutrophils to extravascular tissues where the cells perform their principal host defense functions. To evaluate this possibility we developed a sensitive, reproducible method of measuring the extravascular delivery of neutrophils to a normal mucosal site of neutrophil turnover. This method is based upon the quantification of neutrophils recoverable from saline mouth wash specimens. Twenty-five mL specimens, obtained in a controlled manner from neutropenic patients and normal subjects, were centrifuged and the sediments resuspended in 1.0 mL Hank's buffer with 2 micrograms acridine orange, incubated at 37 degrees C for 15 minutes, and then examined in a hemocytometer chamber by fluorescence microscopy. Neutrophils could be clearly distinguished by their characteristic fluorescence and were counted. With this method as few as 1,500 neutrophils were detected reliably in mouth wash specimens. Mucosal neutrophil counts varied less than 10% with repeated sampling of individual subjects over 5-day periods and were consistently greater than 1.3 X 10(5)/specimen in non-neutropenic individuals. Although profound neutropenia was generally reflected by lower than normal oral mucosal neutrophil counts, these counts were significantly higher in individuals with chronic severe neutropenia (blood neutrophils less than 300/mm3) than in patients with acute neutropenia of comparable severity that had developed following chemotherapy. Also, in individuals recovering from profound neutropenia, neutrophils usually reappeared earlier in mouth wash specimens than in blood, and oral mucosal neutrophil counts attained recovery levels more rapidly than did blood counts. This phenomenon was particularly evident in an individual with cyclic neutropenia. Moreover, mucosal neutrophils could occasionally be detected in profoundly neutropenic patients when neutrophils were not present in blood samples. These findings indicate that mucosal neutrophil counts in individuals with neutropenia provide information about the delivery of neutrophils to tissues that may not be apparent from blood neutrophil counts alone.     

Injury Prevention in Baseball: from Youth to the Pros

Purpose of Review

This review examines recent literature on injury epidemiology and prevention in the sport of baseball from youth to professional levels.

Recent Findings

Overuse is the predominant mechanism of injury in youth baseball players. Newer stretching and exercise protocols may help prevent these injuries. At the professional level, however, overuse has not been proven to correlate with increased injury incidence, but pitch counts are still monitored. There continues to be a rise in operations performed for baseball-related injuries, including ulnar collateral ligament (UCL) reconstruction, particularly in younger athletes. As the level of play increases, there is significant loss of participation due to injuries, such as the UCL in the upper extremity and the hamstrings in the lower extremity.

Summary

Baseball is a widely popular sport, which has led to a focus on injury epidemiology and prevention. While the majority of research regarding baseball injuries focuses on pitchers, fielders and catchers are also at risk. In an attempt to decrease non-contact injuries in the upper and lower extremities, stretching and strengthening exercises are vitally important. Because injury profiles demonstrate significant variability from youth to professional baseball, unique prevention strategies are likely necessary at each level. More research is needed to develop and validate appropriately targeted injury prevention programs.

     

Normal pulmonary artery and branch pulmonary artery sizes in children

To establish standards for pulmonary artery and branch pulmonary artery (PA and BPA) effective diameter (ED) and cross-sectional area (CSA) by using computed tomography (CT) data in children of a wide range of sizes and investigate the roundness of arteries. The ED (average of short and long axes) and CSA for the PA and BPA were measured using 1-mm collimation double-oblique reconstructions. Ordinary least squares regression was used to investigate models with various functional forms that related ED and CSA to patient size. Aspect ratio (AR), the short axis divided by long axis, was measured to evaluate roundness. The ideal diameter derived from CSA measurements was compared to ED, short axis, and long axis measurements. 108 CT examinations were analyzed in children without reason for abnormal PA size who ranged in age from 0 to 18 years (mean, 10.9 years; SD, 5.9 years). Interrater reliability was excellent. Data were modeled using a natural log-transformed response variable and a linear term for height as the independent variable. AR for the PA, right pulmonary artery, and left pulmonary artery measured <?0.9 for 38, 55, and 37%, respectively, indicating that many arteries are not round. Ideal diameter was not significantly different than ED but was for short- and long-axis diameter measurements. Normal ED and CSA for PA and BPA were determined for children of different sizes. Measurements outside of the normal range are consistent with dilatation or stenosis. Single diameter techniques are likely to introduce error.     

Experience in treating persons with HIV/AIDS and the legalization of assisted suicide: the views of Canadian physicians

The objective of this study is to determine the opinions of a random sample of Canadian family physicians and a population of non-specialist physicians known to provide care to persons with HIV/AIDS about the legalization of physician assisted suicide for persons with HIV disease. In addition, we have attempted to ascertain the physician characteristics that may be associated with a favourable or negative opinion. Self-administered, anonymous questionnaires were mailed to 2,890 family physicians across Canada. Logistic regression analysis was used to determine whether physician characteristics were predictive of agreement with the legalization of physician assisted suicide. Of the respondents who had an opinion, 60% agreed with the legalization of physician assisted suicide. Multivariate analyses indicated that physicians who were living in the provinces of British Columbia (BC), Ontario, or Québec (OR = 1.63, 95% CI: 1.10, 2.43) and who provided routine follow-up care (OR = 1.85, 95% CI: 1.30, 2.63) or palliative care (OR 1.66, 95% CI: 1.13, 2.44) to those with HIV disease were more likely to agree with legalization of physician assisted suicide. This analysis demonstrates a strong support for the legalization of physician assisted suicide for persons with HIV disease among physicians experienced in providing care to those affected.