Evaluation of neonatal subglottic stenosis: a 3-year prospective study

Subglottic stenosis is the most common cause of chronic airway obstruction. It results in prolonged tracheal cannulation of infants and children. Following the widespread adoption over the past 20 years of prolonged intubation for respiratory support in neonates, the incidence of acquired subglottic stenosis increased dramatically. On January 1, 1987, we began a 3-year prospective study to delineate potential etiologic factors involved in the development of subglottic stenosis in neonates. The present study analyzes data from 289 infants. Relationships between birth weight, gestational age, endotracheal tube size, duration of intubation and ventilation, number and difficulty of intubations, and the subsequent need for medical and surgical therapy are discussed. Whole organ larynges from autopsy specimens provide histological correlation.     

Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells

PURPOSE: The presence of antigen-presenting cells (APCs) such as Langerhans cells (LCs), an epithelial form of dendritic cells (DCs), in corneal tissue is critical for generation of immune responses, including graft rejection and herpetic keratitis. The purpose of this study was to characterize the distribution and major histocompatibility complex (MHC) antigen expression of corneal LCs. METHODS: Normal and inflamed corneas were excised from BALB/c mice, and immunofluorescence staining for CD11c, CD11b, CD45, CD80 (B7.1), CD86 (B7.2), CD3, and MHC class II (Ia) was performed by confocal microscopy on wholemount corneal epithelium. RESULTS: CD11c(+) MHC class II-positive LCs were found in the limbus and corneal periphery, but not in the center of the normal cornea. These cells were CD45 positive, exhibiting bone marrow derivation, and CD3 and CD11b negative, confirming a DC lineage. Additionally, these cells were CD80 and CD86 negative, reflecting an immature phenotype. In the central and paracentral areas, however, significant numbers of CD11c(+) LCs were detected that expressed no MHC class II. It is important to note that although the density of the LCs declined from the limbus toward the center of the cornea, they were always present. In the inflamed cornea, the expression of MHC class II and costimulatory molecules CD80 and CD86 was significantly enhanced, and present in all parts of the cornea, in contrast to the normal cornea. CONCLUSIONS: The present study demonstrates for the first time the phenotype and distribution of MHC class II-negative LCs in the murine corneal epithelium. In the inflamed cornea, the LCs become activated as reflected by expression of B7 costimulatory markers. These changes in activation markers may provide additional information for devising novel immunomodulatory strategies.     

Calcium channel blocking activity of thioridazine,clomipramine and fluoxetine in isolated rat vas deferens: a relative potency measurement study

PURPOSE: We evaluated the calcium channel blocking activity of thioridazine, clomipramine and fluoxetine in isolated rat vas deferens and determined their relative order of potency. MATERIALS AND METHODS: Cumulative control concentration-response curves to calcium chloride were obtained in isolated rat vas deferens incubated in depolarizing calcium-free Krebs-Henseleit solution. Tissues were washed to baseline length and equilibrated with a given concentration of test drugs. After a 30-minute period a calcium concentration-response curve was repeated. The resulting rightward displacement of the concentration-response curve to calcium provided a dose ratio. The dose ratio was used in the Schild equation and the antagonism of calcium induced contractions was quantified by Schild analysis. RESULTS: The calcium channel blocking activity of thioridazine, clomipramine and fluoxetine was compared with nifedipine. All 4 drugs produced parallel rightward displacement of concentration-response curves to calcium. The potency of this effect was quantified by Schild analysis showing pA estimates, namely nifedipine 7, thioridazine 6.2, clomipramine 5.65 and fluoxetine 5. CONCLUSIONS: A characteristic profile of calcium channel blocking activity on the vas deferens was obtained for all test drugs. The relative order of potency was determined as thioridazine greater than clomipramine greater than fluoxetine. Differences in the potency of calcium entry blockade at peripheral end organs may contribute to differential effects of these drugs on delaying ejaculatory latency in patients with premature ejaculation.     

A forearm exercise screening test for mitochondrial myopathy

BACKGROUND: The authors hypothesized that impaired oxygen extraction in mitochondrial myopathy (MM) results in a high oxygen saturation in venous effluent blood from working muscle and that this phenomenon can be used as a diagnostic tool for MM. METHODS: Twelve patients with MM, 10 patients with muscular dystrophy, and 12 healthy subjects were studied. All subjects performed intermittent static handgrip exercise (1/2 Hz) at 40% of maximal voluntary contraction (MVC) for 3 minutes. Cubital venous oxygen saturation and brachial artery flow were measured in the exercised arm. RESULTS: Exercise-induced venous oxygen desaturation was smaller in patients with MM (Delta - 7 +/- 5%) than in subjects with muscular dystrophy (Delta - 38 +/- 2%; p = 0.00001) and healthy subjects (Delta - 43 +/- 2%; p = 0.0000002). MVC and exercise blood flow were similar in patients with MM (18 +/- 3 kg; 436 +/- 65 mL/min) and patients with muscular dystrophy (15 +/- 3 kg; 460 +/- 85 mL/min), but were higher in healthy subjects (32 +/- 4 kg; 630 +/- 58 mL/min; p < 0.03). In seven patients with MM and seven patients with McArdle disease, studied with a slightly different protocol, exercise-induced oxygen desaturation was also impaired in MM (Delta - +/- 5%) compared with McArdle disease (Delta - 26 +/- 3%; p = 0.007). CONCLUSION: Oxygen desaturation in venous blood from exercising muscle is markedly lower in patients with mitochondrial myopathy than in subjects with other muscle diseases and healthy subjects, suggesting that a forearm exercise test can be a diagnostic screening tool for mitochondrial myopathy.     

Achlorhydria, parietal cell hyperplasia, and multiple gastric carcinoids: a new disorder

We describe a 54-year-old woman who had multiple gastric carcinoid tumors arising in the setting of marked hypergastrinemia associated with a lack of acid production by hypertrophic parietal cells. The serum gastrin level was 1,400 pg/mL, and investigation revealed no evidence for either of the recognized causes for hypergastrinemia-associated carcinoids, autoimmune gastritis, and Zollinger-Ellision syndrome. Partial gastrectomy was performed. Pathologic examination showed multiple intramucosal and invasive carcinoid tumors of the body and fundus in a background of marked ECL cell hyperplasia. There were no gastric or duodenal ulcerations. One perigastric lymph node was metastatically involved. The oxyntic mucosa showed marked hyperplasia and hypertrophy of the parietal cells. Some of these cells were vacuolated, and many displayed protrusions of apical cytoplasm into dilated oxyntic glands filled with inspissated eosinophilic material. Similar findings have occurred in 1 other patient, strongly indicating that the clinicopathologic alterations in the 2 cases are not random but, on the contrary, represent a very rare disorder of gastric carcinoids associated with an intrinsic acid secretion abnormality of the parietal cells.     

Separate cavity margin sampling at the time of initial breast lumpectomy significantly reduces the need for reexcisions

In breast conservation therapy, the margin status of the specimen predicts local recurrence and determines the need for reexcision. Many surgeons now take, at the time of lumpectomy, multiple separate "cavity margins" (CM) (the entire wall of the residual cavity) as final margins that supersede the oriented lumpectomy margins (LMs). We studied the efficacy of this method in 126 patients (23 with ductal carcinoma in situ [DCIS] only and 103 with invasive carcinoma with or without DCIS) who had an oriented lumpectomy specimen and also had four to six additional CMs. The tumors were evaluated for the following: size, grade, LM status (distance of tumor from margin and, if involved, extent of involvement), vascular invasion, lymph node status, and presence or absence of extensive intraductal component. The additional CM specimens were evaluated for residual carcinoma (if any) and its distance from the inked true margins, and the results were correlated with the corresponding LMs. Only approximately 50% of patients (52 of 103) with histologically positive LMs (defined as carcinoma within 2 mm of the inked surface) had residual carcinoma in their CMs. Additional CM sampling rendered the overall final margin status histologically negative in 61 of 103 (59%) cases with histologically positive LMs, therefore significantly reducing the need for reexcision. Younger patient age, higher number of positive LMs, high tumor grade, and the presence of extensive intraductal component were predictive of residual carcinoma in CM specimens, whereas the distance of carcinoma from the inked surface and the extent of tumor involvement of histologically positive LMs were not. Because CM specimens taken from patients with histologically positive LMs usually lack tumor, we suspect that many positive LMs are likely false positives. Possible factors accounting for false-positive LMs include seepage of ink into crevices of the specimen promoted by excessive inking, tumor friability promoting displacement of tumor into ink, manipulation of specimens for radiographs, and retraction artifact.