Next Congress brings challenges.
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Biomedical subjects
Publications and source records attributed to M J Rock.
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This report describes a 7 year old girl who presented with scoliosis and a small right hemithorax. Findings on spine roentgenographs were pleural thickening on the right and parenchymal densities. Computed tomography of the chest and abdomen revealed multiple pulmonary nodules and two hypervascular lesions within the liver. The diagnosis established by lung biopsy was intravascular bronchioloalveolar tumor (epithelioid hemangioendothelioma of the lung). This is the youngest reported case of this rare tumor.
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Alveolar macrophages (AMs) and mast cells reside in the airway, and both have been demonstrated to contribute independently to allergic inflammatory responses through the generation of respiratory-burst metabolites and the release of biologically active mediators, respectively. Since mast cell granules (MCGs) contain mediators that could potentially interact with the AM respiratory burst, we investigated the effects of isolated MCGs on this important inflammatory pathway of the AM. MCGs and AMs were obtained by peritoneal and tracheoalveolar lavage, respectively, of Sprague-Dawley rats. First, the overall respiratory-burst activity was measured by luminal-enhanced chemiluminescence (CL), and second, the individual oxygen species contributing to CL (superoxide anion [O2-], hydrogen peroxide [H2O2], and hypochlorous acid) were measured. MCGs alone enhanced AM CL responses to an equivalent degree compared to zymosan-stimulated AMs. However, AMs preincubated with MCGs followed by zymosan stimulation significantly and synergistically enhanced the CL responses. This enhanced CL was not due to an increased production of O2-, H2O2, or hypochlorous acid; in fact, there were decreased measured amounts of O2- and H2O2 from zymosan-stimulated AMs in the presence of MCGs, most likely caused by the content of granules of superoxide dismutase and peroxidase, respectively. The lipoxygenase inhibitor, nordihydroguaiaretic acid, completely abolished the enhanced CL of AM preincubated with MCGs and subsequently stimulated by zymosan, but O2- production was not affected by nordihydroguaiaretic acid. Taken together, these results suggest that derivatives of arachidonic acid metabolism, most likely those of the lipoxygenase pathway, are responsible for the enhanced AM CL response observed in the presence of MCGs. Thus, mast cell-macrophage interactions may be important within the airway in enhancing the generation of mediators that contribute to tissue inflammation and bronchospasm.
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Detection of elevated levels of immunoreactive trypsinogen (IRT) in dried neonatal blood spots has been used as a screening test for cystic fibrosis. In other cystic fibrosis newborn-screening studies, a sweat chloride test is generally performed only if an infant has a persistent IRT level above a selected cutoff value on both the initial and subsequent specimens. Neither the timing of the second specimen nor the value of the cutoff point for the second specimen has been comprehensively evaluated. In this randomized, controlled study, 145,024 infants were screened in the neonatal period for cystic fibrosis using the 99.8 percentile (180 ng/mL) as the neonatal cutoff point. A total of 129 infants had elevated neonatal IRT levels and had negative results on sweat tests (false-positive by IRT screening). A total of 54 children with cystic fibrosis were identified in the screened and comparison groups. Excluding patients with meconium ileus, 4 infants with cystic fibrosis had neonatal IRT values less than 180 ng/mL, and an additional 9 infants with cystic fibrosis had values decline to less than 180 ng/mL within the first 2 1/2 months of age. The IRT values of infants with and without cystic fibrosis overlapped considerably beyond 30 days of age. These findings suggest that further refinement of cystic fibrosis screening methodology will be necessary to achieve an acceptable sensitivity and specificity.
Blood immunoreactive trypsinogen (IRT) is elevated in newborns with cystic fibrosis (CF) and has been used as a neonatal screening test. However, not only is the benefit of early diagnosis unknown, but also the sensitivity, specificity, and time related decline of IRT values have yet to be comprehensively evaluated. This report describes the characteristics of infants with a false-positive IRT in our experience with CF screening of 87,000 infants. The IRT value was elevated in 92 newborns; 13 had a confirmed diagnosis of CF by quantitative pilocarpine iontophoresis sweat testing, and 79 infants did not have CF and were therefore classified as false positives by IRT screening. In order to test the hypothesis that perinatal stress factors are associated with high neonatal IRT values, we evaluated Apgar scores at 1 and 5 minutes. We found that the scores of false-positive infants were significantly lower (P = 0.0004 and P = 0.0102 at 1 and 5 minutes, respectively), compared with infants in the general population. While perinatal asphyxia as reflected by low Apgar scores is an associated factor accounting for an elevated IRT value, the majority of non-CF newborns with an elevated IRT have normal Apgar scores.
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The effect of aerosolized ketamine hydrochloride was investigated by measuring airway resistance with a two-compartment plethysmograph in guinea pigs challenged with histamine. In the first phase of the study, treatment with ketamine prior to histamine challenge did not protect against elevation of airway resistance. In the second phase of the study, ketamine inhalation after histamine challenge did not significantly diminish airway resistance. Aerosolized ketamine is not recommended for use in human subjects with asthma.
Bronchomalacia has not previously been described in association with Larsen syndrome. In this article, three children with Larsen syndrome are reported. All three patients have tracheomalacia, and one of them has diffuse bronchomalacia diagnosed at flexible fiberoptic bronchoscopy. The patients' symptoms of airway obstruction include stridor, cyanosis, apnea, and recurrent pneumonias. Recognition of these abnormalities may allow the institution of supportive therapy.
We treated two pediatric patients suffering respiratory failure associated with status asthmaticus. Neither patient responded to maximal bronchodilatory therapy and mechanical ventilation; however, continuous infusion of ketamine (1.0 to 2.5 mg/kg X h) immediately improved airway obstruction. Ketamine appears to increase catecholamine levels and directly relax bronchial smooth muscle. Except for increased secretions during the infusion, our patients showed no immediate or long-term sequelae from ketamine therapy. However, ketamine should only be used for asthmatics whose respiratory failure does not respond to conventional management and mechanical ventilation.
Asthma is one of the most common chronic medical conditions affecting children. The usual presenting symptoms of asthma include wheezing, shortness of breath, and dyspnea on exertion. Occasionally, children who present with one of these respiratory complaints have a less common disorder. Mediastinal fibrosis is a rare and incurable condition in which an excessive fibrotic reaction in the mediastinum causes progressive cardiopulmonary compromise. The presentation is variable: many patients present with respiratory symptoms such as cough, wheezing, dyspnea, and/or hemoptysis, while others are asymptomatic and present with a mediastinal mass discovered incidentally on a radiograph. With such a broad array of presenting complaints, and a clinical course characterized by slow progression of symptoms, the early stages of mediastinal fibrosis can mimic other diseases such as asthma, chronic bronchitis, or the superior vena cava syndrome. In this report we describe two patients with mediastinal fibrosis who were initially thought to have asthma.