Bronchiolitis: update 2001

In this review, reports from last year on the following topics are summarized: (1) reviews of bronchiolitis in infants; respiratory syncytial virus (RSV)-associated illness, including possible viral mechanisms of alteration of airway function and results of an epidemiologic study of bronchiolitis-associated mortality. Studies evaluating (2) the use of serum eosinophilic cationic protein as a marker for development of subsequent persistent wheezing infants; (3) parental bronchial responsiveness as an indicator of genetic susceptibility to acute bronchiolitis; (4) prophylactic use of monoclonal antibody (Palivizumab) to control an outbreak of RSV in a hospital nursery; (5) a controlled clinical trial of ribaviron in acutely ill children; (6) reports of new associations with bronchiolitis obliterans organizing pneumonia (BOOP); (7) case reports of use of methotrexate as an alternate to corticosteroids in treatment of BOOP; (8) a newly described entity, eosinophilic bronchiolitis.     

Characteristics of atherosclerotic plaque distribution in coronary artery bifurcations: an intravascular ultrasound analysis

OBJECTIVE: Vessel bifurcations are prone to atherosclerotic plaque accumulation. Using volumetric intravascular ultrasound analysis, we investigated atheroma distribution at human coronary bifurcations in vivo. METHODS: We analyzed plaque distribution in 49 left anterior descending coronary artery-diagonal and 20 left circumflex coronary artery-obtuse marginal bifurcations with <50% angiographic stenosis. Cross-sections were analyzed at 1 mm intervals in segments 5 mm proximal and distal from the bifurcation. Planimetry of the lumen and external elastic membrane (EEM) was performed and plaque thickness measured at four different points relative to the branch: 0 degrees, 90 degrees, 180 degrees and 270 degrees. EEM, lumen and plaque volume and percentage plaque burden (plaque volume/EEM volume) were calculated in the proximal and distal segments. The side-branch take-off angle was analyzed in the cross-sectional images. RESULTS: Volumetric analysis showed that EEM, lumen and plaque were larger (P<0.001) in proximal segments than distal segments, whereas percent plaque burden was similar in these segments. Plaque accumulated on the opposite wall to the flow divider. Plaque distribution tended to be more eccentric in distal segments (P=0.05) compared to proximal segments. In 26 of 69 lesions, an asymmetric side-branch take-off was found and was associated with asymmetric plaque distribution compared to those lesions that had a symmetric side-branch take-off (P<0.01). CONCLUSION: We found characteristic patterns of plaque distribution at coronary bifurcations. Proximal segments demonstrated larger plaque volume than distal segments, despite similar percentages of plaque burden. Plaque volume accumulated opposite to the flow divider, especially in distal segments. The side-branch take-off angle in the cross-sectional plane influenced the plaque distribution in bifurcation lesions.     

Nonuniformity of the transmural distribution of coronary blood flow during the cardiac cycle. In vivo documentation by contrast echocardiography

This study was performed to examine the transmural (endocardial vs. epicardial) heterogeneity of myocardial blood flow during the cardiac cycle (systole vs. diastole). Twenty-four contrast echocardiographic injections were performed in seven open-chest anesthetized dogs either into left anterior descending or circumflex coronary artery or into the aortic root. Two-dimensional echocardiography in short-axis view was performed and was digitized off-line into a 256 x 256 pixel matrix with 256 gray levels/pixel. All end-diastolic and end-systolic frames before and to peak contrast were analyzed. A region of interest corresponding to the most intensely opacified myocardial segment was traced, the mean videodensity measured, and the frame of initial contrast appearance detected. The region of interest was divided into three equal parallel layers corresponding to the endocardial, midcardial, and epicardial myocardium. When the echocardiographic contrast effect initially appeared in diastole, the increment in videodensity was greater for the endocardium (131 +/- 48%) than for the epicardium (71 +/- 37% of the increment in videodensity of the entire wall) (p less than 0.05). This inhomogeneity subsequently disappeared in the following end-systolic frame. When the initial echocardiographic contrast effect appeared in systole, intensity was higher in epicardium (136 +/- 83%) than in endocardium (60 +/- 60%) (p less than 0.05). However, in the following diastole, intensity was not significantly different for the two layers. Thus, myocardial contrast echocardiography demonstrates that coronary blood flow is primarily subendocardial in distribution during diastole and subepicardial during systole.     

Activator of G protein signaling 3 null mice: I. Unexpected alterations in metabolic and cardiovascular function

Activator of G protein signaling (AGS)-3 plays functional roles in cell division, synaptic plasticity, addictive behavior, and neuronal development. As part of a broad effort to define the extent of functional diversity of AGS3-regulated-events in vivo, we generated AGS3 null mice. Surprisingly, AGS3 null adult mice exhibited unexpected alterations in cardiovascular and metabolic functions without any obvious changes in motor skills, basic behavioral traits, and brain morphology. AGS3 null mice exhibited a lean phenotype, reduced fat mass, and increased nocturnal energy expenditure. AGS3 null mice also exhibited altered blood pressure control mechanisms. These studies expand the functional repertoire for AGS3 and other G protein regulatory proteins providing unexpected mechanisms by which G protein systems may be targeted to influence obesity and cardiovascular function.     

Gastropexy and “Fundoplication” in surgical treatment of hiatal hernia

Summary The rationale and indications for gastropexy plus fundoplication in the surgical treatment of esophageal hiatal hernia are discussed. This intervention—considerably simpler than any method used hitherto—also appears to produce satisfactory long-term results.Wrapping the fundus around the distal portion of the esophagus.This paper was submitted as part of the special European issue edited by Ernst Hafter (Am. J. Dig. Dis., Vol.6, No. 7, 1961).     

Immunostimulatory effects of different antilymphocyte globulin preparations: a possible clue to their clinical effect

Antilymphocyte globulin (ALG) and antithymocyte globulin (ATG) have an established role in the treatment of severe aplastic anaemia. The response rate ranges from 40% to 80%. Its mode of action is believed to be complement dependent lysis of immunocompetent cells which inhibit haemopoietic maturation. This might not be the sole mechanism. We have tested four different preparations of ALG/ATG for their mitogenic effect on normal peripheral blood cells and on enriched T-cells in vitro by 3H-thymidine incorporation. We found marked differences between the four preparations. One was strongly mitogenic and able to induce profound release of haemopoietic growth factors. This mitogenic effect could be detected in the serum of patients during ALG treatment. Clinical response rates of this preparation are about 80%. Three other preparations were of lower or no stimulatory effect. Clinical response rates with these preparations vary between 40% and 60%. From our results, we postulate that the beneficial effect of ALG could be partially due to its ability to stimulate release of haemopoietic growth factors. The mitogenicity of different ALG/ATG preparations should be tested as an in vitro parameter of clinical efficacy.     

Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis

Eosinophils are effector cells that play an important role in the damage induced by the allergic process by releasing inflammatory mediators and proteolytic factors after activation. Stem cell factor (SCF) is a primary cytokine involved in hematopoiesis and mast cell differentiation, proliferation, and activation. Studies have also indicated that SCF is directly involved in pathogenesis of allergic airway inflammation. In the present study, we examined the ability of SCF to activate murine eosinophils for increased mediator release and up-regulation of chemokines. Initial data demonstrated that eosinophils have significant levels of surface c-kit protein, SCF receptor. SCF-activated eosinophils degranulate and release eosinophil peroxidase and leukotriene C(4) in a dose-dependent manner. In addition, SCF was further shown to induce the release of CC chemokines, RANTES, macrophage-derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and C10 from eosinophils. To identify the extent of SCF-induced activation of eosinophils, we also performed gene array analysis using an array containing 1153 genes related to inflammation, including cytokines and their receptors, growth factors, structural and cytoskeletal genes, signal transduction genes as well as several other classes related to immune/inflammatory responses. The gene analysis indicated that more than 150 genes were significantly up-regulated in eosinophils after SCF stimulation. The gene array results were verified using a quantitative real-time polymerase chain reaction analysis to identify the expression of several chemokine and chemokine receptor genes. Altogether, these studies indicate that SCF is a potent eosinophil degranulator and activator that may play a number of roles during an inflammatory/immune response.     

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient’s immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51 ± 6% for group A and 61 ± 7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.