Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

Holt-Oram syndrome associated with the hypoplastic left heart syndrome

We present the first case of Holt-Oram syndrome associated with the lethal congenital heart defect of hypoplastic left heart syndrome. The possible pathophysiological link is explored and the need for careful genetic and cardiologic evaluation in these patients is reiterated.     

Autoantibodies against the serotoninergic 5-HT4 receptor and congenital heart block: a reassessment

The specificity of autoantibodies against the serotoninergic 5-HT4 receptor in congenital heart block has led to conflicting observations. In order to clarify the situation, a collaborative effort was undertaken to discover the reasons for these discrepancies and to reassess the importance of such autoantibodies by making use of the Research Registry for Neonatal Lupus. Sera from 128 patients (101 anti-SSA/Ro52 positive mothers among which 74 have children with congenital heart block (CHB), 9 anti-SSA/Ro52 negative patients of which 1 had a child with heart block and 18 healthy donors) were assessed in a single blind test using an ELISA coated with a 5-HT4 receptor-derived peptide. Discrepancies between previous observations in our two groups could be ascribed to small differences in the set up of the assay. Of the 75 sera from mothers of children with CHB, 12 were reactive with the 5-HT4 peptide. Four sera among which three were from 35 Ro52 negative mothers without affected children as well as 2 in the 18 controls were positive. Interestingly, in 1 mother with an isolated child with CHB but who had no detectable anti-SSA/Ro52 antibodies and 1 mother with a child with a structural heart block and no detectable antibodies to any component of SSA/Ro, reactivity with the 5-HT4 receptor was noted. While 5-HT4 receptor autoantibodies do not have the predictive value of anti-Ro52 autoantibodies, the presence of these antibodies in a minor subset of mothers whose children have CHB suggests an additional risk factor which may contribute to the pathogenesis of disease.     

Pulmonary immunity to Pseudomonas aeruginosa in intestinally immunized rats roles of alveolar macrophages, tumor necrosis factor alpha, and interleukin-1 alpha.

The aims of this study were to assess the role played by alveolar macrophages, tumor necrosis factor alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) in pulmonary immunity against Pseudomonas aeruginosa in animals that have been immunized via the gut-associated lymphoid tissue. Following intra-Peyer's patch immunization and subsequent intratracheal challenge with live bacteria, significantly enhanced bacterial clearance from the lungs correlated with an increase in bronchoalveolar neutrophils, increased recruitment and phagocytic activity of alveolar macrophages, and accelerated production of TNF-alpha in the bronchoalveolar space, while levels of IL-1 alpha remained low. Administration of recombinant TNF-alpha in physiological concentrations did not affect the proliferation of P. aeruginosa in vitro, but when given intratracheally to rats at the time of infection, recombinant TNF-alpha significantly increased bacterial clearance from the lungs. In these animals, phagocytic activity of bronchoalveolar neutrophils was enhanced, while the recruitment of alveolar macrophages and neutrophils remained unchanged. In acutely infected nonimmune animals, bronchoalveolar concentrations of soluble IL-1 alpha and TNF-alpha increased until the time of death. Levels of prostaglandin E2 and thromboxane B2 were similar in each experimental group. These results indicate that infection in immune animals enhanced both recruitment and phagocytic activity of alveolar macrophages as well as induced an accelerated production of TNF-alpha. In immune challenged animals, this cytokine enhanced the phagocytic activity of neutrophils and improved bacterial clearance from the lung. Levels of soluble IL-1 alpha and TNF-alpha in nonimmune rats increased consistently following infection until the time of death, thus implicating these cytokines in the pathogenesis of acute P. aeruginosa pneumonia.     

A possible role for lysozyme in determining acute exacerbation in chronic bronchitis.

The aggregation of non-serotypable Haemophilus influenzae (NTHI) by whole saliva from patients with chronic obstructive lung disease (COLD) was investigated. Significant differences were observed between salivary aggregating activity of a control and COLD population (P < 0.001). Saliva from patients less prone to acute exacerbations had a greater capacity to aggregate bacteria compared with saliva from patients with a predilection to infection. The mechanism of saliva-mediated aggregation of NTHI was investigated and shown to be related to lysozyme content. Lysozyme activity in saliva was measured by the turbidimetric technique and results showed that patients with chronic bronchitis had increased levels of salivary lysozyme, with a subpopulation within the non-infection-prone group having greater amounts. A significant difference was observed in salivary lysozyme between controls and non-infection-prone (P < 0.005) and infection-prone (P < 0.05) patients, respectively: the non-infection-prone patients having significantly (P < 0.005) more than the infection-prone patients. There was significant correlation (r = 0.742, P < 0.001) between salivary aggregation of NTHI and lysozyme activity. Chromatographically purified human lysozyme had a similar aggregation profile to that of saliva. There was no difference in serum and saliva lactoferrin concentrations between groups, but there was a significant increase (P < 0.05) in serum lysozyme concentration in the non-infection-prone group. This study suggests that the level of salivary lysozyme derived from macrophages may play an important role in determining resistance or susceptibility to acute bronchitis.     

Activation of airway cl- secretion in human subjects by adenosine

We investigated cystic fibrosis (CF) transmembrane conductance regulator (CFTR) regulation by A2 adenosine (Ado) receptors and beta2 adrenergic receptors in CFTR-corrected CFBE41o- airway cells and human subjects. CFBE41o- cells stimulated with Ado (10 microM), isoproterenol (Iso, 10 microM), or Ado + Iso (10 microM each) elevated cyclic AMP (cAMP) above control conditions (P < 0.001), with the Iso conditions increasing cAMP approximately 10-fold above that produced by Ado alone (P < 0.001). All agonist conditions had similar effects on short circuit current at 10 and 25 microM, with no further currents produced by subsequent stimulation with forskolin (20 microM). CFTR dependence was demonstrated by glybenclamide block of agonist-stimulated currents. Nasal potential difference studies in normal (n = 50) subjects demonstrated that Ado (10 microM) and Ado + Iso (10 microM each) produced more polarization compared with Iso (10 microM Ado increase = 44%, 10 microM Ado + Iso increase = 52%, P < 0.05 for each condition compared with Iso alone). Studies completed in patients with CF (n = 10, "severe" genotypes) confirmed that Ado-stimulated polarization was CFTR-dependent. Together, these results indicate that Ado is a potent Cl- secretagogue in vivo, with relatively small effects on cAMP levels despite strong effects on CFTR-dependent short circuit current and nasal Cl- transport. These findings support growing evidence indicating a role for Ado regulation of CFTR-dependent Cl- secretion in vivo.