Controversies in the management of children with bronchiolitis

In this review, we present and summarize data from recently conducted research regarding controversial aspects of the management of children with bronchiolitis. These data suggest that chronic medical history, gestational age at birth, postnatal age, and physiological variables can identify those children at higher risk for a more severe course of bronchiolitis. Large prospective studies also suggest that the likelihood of significant bacterial illness in febrile infants with bronchiolitis may be lower than in children without bronchiolitis. Nevertheless, urinary tract infections remain relatively common in young febrile children with bronchiolitis. Lastly and unfortunately, the data note a relative lack of effective therapies for children with bronchiolitis, although certain therapies such as systemic corticosteroids show potential efficacy and are in need of further study. The remaining uncertainty surrounding many issues pertaining to bronchiolitis highlight the need for more research aimed to: (1) develop prognostic models to identify patients at risk for a more severe clinical course, (2) develop generalizable diagnostic models to identify febrile infants with bronchiolitis at high and very low risk of significant bacterial illness, and (3) evaluate the effectiveness of promising therapies.     

Disseminated tuberculosis presenting as multiple hepatosplenic microabscesses and pancytopenia in a teenage boy.

Disseminated tuberculosis usually occurs in immunocompromised hosts. Involvement of bone marrow, liver, and spleen is infrequent. A previously healthy 15-year-old boy presented with body weight loss, prolonged fever, neck lymphadenopathy, pancytopenia, and hepatosplenic microabscesses within the recent month and was transferred to our hospital. Bone marrow studies showed hypocellular marrow. Based on his clinical manifestations, hemophagocytic syndrome was initially suspected. Pancytopenia resolved after administration of intravenous immunoglobulin but caseous necrosis and/or positive acid-fast stain were subsequently demonstrated in the lymph node biopsy and sputum. Cultures from these 2 specimens grew Mycobacterium tuberculosis. Fever continued in a low-grade pattern even under antituberculous therapy with rifampin, isoniazid, pyrazinamide and ethambutol. Five months after admission, fever subsided after splenectomy and liver wedge resection. Microscopic examinations of both the liver and spleen showed mycobacteria-related granulomatous inflammation and caseating necrosis. This report suggests that tuberculosis infection should be considered in the differential diagnosis in patients with prolonged fever, pancytopenia and hepatosplenic abscesses.     

Six-month nocturnal nasal positive pressure ventilation improves respiratory muscle capacity and exercise endurance in patients with chronic hypercapnic respiratory failure.

BACKGROUND/PURPOSE: This study was designed to investigate the effects of 6 months of nocturnal nasal positive pressure ventilation (NNPPV) on respiratory muscle function and exercise capacity in patients with chronic respiratory failure. METHODS: A prospective, randomized, controlled design was used. Twenty-nine patients with chronic respiratory failure were enrolled and allocated to either the NNPPV (n = 14) or control group (n = 15). Patients in the NNPPV group received bi-level positive pressure ventilation via nasal mask for 6 consecutive months. Arterial blood gas, respiratory muscle assessment and 6-minute walk test (6MWT) were performed before and after the 6-month NNPPV intervention. Respiratory muscle function was assessed using the variables of maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and maximum voluntary ventilation (MVV). RESULTS: Subjects in the NNPPV group showed a significant improvement in blood gas exchange and increased 6-minute walk distance (6MWD) compared to baseline and the control group. The 6MWD was significantly increased from 257.1 +/- 114.1 to 345.2 +/- 109.9 m (34.3%) in the NNPPV group. NNPPV also significantly improved MVV and Pimax relative to baseline. MVV was significantly increased from 19.2 +/- 6.5 to 22.3 +/- 7.1 L/min (16.1%) in the NNPPV group (p < 0.05). Furthermore, there was a significant correlation between the magnitude of MVV improvement and 6MWD change. CONCLUSION: The 6-month NNPPV treatment significantly decreased the partial pressure of carbon dioxide and improved daytime respiratory muscle function, thus contributing to exercise-capacity increase in patients with chronic respiratory failure.     

Dome-shaped high tibial osteotomy: a long-term follow-up study.

BACKGROUND: High tibial osteotomy (HTO) is a well-established treatment for unicompartmental gonarthrosis of the knee, but its durability and complications remain controversial. We previously introduced a novel dome-shaped HTO, and the long-term follow-up results using this technique are analyzed in this study. METHODS: We treated 25 varus knees in 22 patients with medial gonarthrosis, using a specially designed calibrated cutting jig along with rigid external fixation and early joint motion postoperatively. A total of 16 patients (19 knees) completed the study protocol and were followed up for 13-16 years (mean, 15 years). RESULTS: The surgery attempted to obtain 8 degrees valgus; the actual postoperative alignment averaged 12.4 degrees valgus, which decreased significantly to 7.8 degrees valgus after 5 years. The outcome as assessed by the Hospital for Special Surgery knee score was excellent or good in 18 knees at 5 years postoperatively, and in 13 knees at the final follow-up, showing a significant deterioration with time. Loss of correction with time was not correlated with the postoperative alignment achieved: at 5 years, loss greater than 2 degrees was found in 12 knees, but their mean corrected angle (11.8 degrees valgus) was not significantly different from that of the others (13.3 degrees valgus). Nor was the loss of correction correlated with the knee scores. The mean amount of joint motion after surgery did not change significantly with time: 124 degrees preoperatively and 114 degrees at the final follow-up. The patellar position also did not change from preoperative values during postoperative follow-up: mean Insall-Salvati index was 0.88 before and 0.90 5 years after surgery, neither showing patella baja. CONCLUSION: Dome-shaped HTO is a durable time-buying procedure for patients with unicompartmental medial gonarthrosis, and can avoid subsequent development of patella baja that may complicate further prosthetic arthroplasty.     

The HOPA Gene Dodecamer Duplication Is Not a Significant Etiological Factor in Autism

A recent study has suggested that a dodecamer duplication in the HOPA gene in Xq13 may occur in a significant portion of male patients with autism. We have determined the incidence of this duplication in 202 patients from the South Carolina Autism Study. The incidence of the duplication was not significantly different between patients and controls. Three of the female patients inherited the duplication from nonautistic fathers. In addition, there was no systematic skewing of X inactivation in the female patients with the duplication, or in nonautistic mothers and sisters with the duplication. These findings suggest that the dodecamer duplication in the HOPA gene does not play a significant role in the etiology of autism.     

Bi-directional interactions between visual areas in the awake behaving cat

The study of the cooperativity among cortical areas is essential to our understanding of brain functioning. Here we investigated the relative contributions of top-down and bottom-up directed interactions between area 17 and area 7 of the cat visual system. Bipolar local field potentials were recorded while the animals performed a go/no-go task or were in a quiet resting state. The data were analyzed by applying measures of interaction based on the Wiener-Granger causality concept. We found that during the visual task top-down directed interactions were of a similar magnitude as the bottom-up component. Second, interareal couplings tended to increase in conditions requiring a discriminative effort. Third, during behaviors not dominated by visual processing non-directed interactions increased.     

Chemoreflexes: an experimental study

HYPOTHESIS: Transmyocardial laser revascularization (TMLR) will not denervate the heart, because it does not destroy all of the afferents. This study was designed to determine if stimulation of cardiac sympathetic and vagal afferents from an area of the left ventricle treated with TMLR could evoke reflex effects, and thus whether TMLR would denervate the heart. METHODS: The effect of TMLR on reflexes evoked by chemically stimulating cardiac afferents was examined in 9 dogs. Bradykinin and capsaicin were applied topically or injected into the left anterior descending coronary artery before and after TMLR and after bilateral vagotomy and sympathectomy. Aortic (AoP) and left ventricular pressures (LVP) and electrocardiography were monitored. The first derivatives of LVP (dP/dt) were calculated. RESULTS: Topical bradykinin elicited variable hemodynamic responses. Topical capsaicin evoked pressor responses, increasing mean (+/- SEM) AoP (105+/-9 to 115+/-9 mm Hg; P<.001) and positive dP/dt (+dP/dt) (1032+/-81 to 1159+/-10 mm Hg/s; P<.01) before TMLR. Intracoronary capsaicin evoked a depressor response before TMLR. Pressor responses remained intact after TMLR with increases in mean AoP and +dP/dt (115+/-6 to 128+/-5 mm Hg and 1039+/-98 to 1136+/-100 mm Hg/s, respectively; P<.01). Depressor responses also remained intact after TMLR (91+/-10 vs 101+/-11 mm Hg [P<.02], and 865+/-104 vs 931+/-104 mm Hg/s [P<.05], respectively). Hemodynamic responses were diminished after bilateral vagotomy and abolished after bilateral sympathectomy. CONCLUSION: Since activation of cardiac afferent nerves and reflex responses remained intact after TMLR, but changed after vagotomy or sympathectomy, TMLR does not denervate the heart sufficiently to be the cause of improved angina after TMLR.     

Rhodostomin inhibits thrombin-enhanced adhesion of ROS 17/2.8 cells through the blockade of alphavbeta3 integrin.

Osteosarcoma is a very malignant bone tumor which has a high metastatic potential and usually lead to poor prognosis. The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated the effect of thrombin on the adhesion activity of the osteosarcoma cell line, ROS 17/2.8. Incubation with the low concentrations of thrombin (0.01-5 U/ml, 5 min to 24 h) elevated the adhesion activity of ROS 17/2.8 to both human umbilical vein endothelial cells (HUVEC) and extracellular matrix, with the peak effect at the concentration of 0.5 U/ml for 30 min at 37 degrees C. The ROS 17/2.8 cells responded to thrombin by a peak effect of increased adhesion to HUVEC (5.5 folds vs. control) and fibronectin (4.8 folds) after thrombin pretreatment (0.5 U/ml, 30 min, 37 degrees C). Pretreatment with monoclonal antibodies against beta3 integrins, including anti-alphavbeta3, 10E5 and 7E3, effectively antagonized the thrombin-enhanced cell adhesion activity, whereas anti-alpha3beta1 and anti-alpha5beta1 did not antagonize the enhanced cell adhesion. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, and synthetic peptide RGDS also blocked the thrombin-enhanced ROS 17/2.8 cell adhesion. This study demonstrated that thrombin enhanced the cell adhesion of ROS 17/2.8 cells to HUVEC or ECM through an upregulation of beta3 integrins, and rhodostomin was a strong inhibitor on thrombin-enhanced cell adhesion, either to HUVEC or fibronectin substratum.     

Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

BACKGROUND: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). METHODS: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. RESULTS: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). CONCLUSION: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.