A comparison of the functional difficulties in staged and simultaneous open carpal tunnel decompression.

There is no agreement about whether patients with bilateral carpal tunnel syndrome should undergo staged or simultaneous open decompression. The purpose of this study was to quantify and compare the functional difficulties during the recovery from surgery for patients undergoing staged or simultaneous decompressions. Sixty-three patients had surgery; 33 had staged decompression (Group 1) and 30 simultaneous decompressions (Group 2). Functional difficulties were recorded using the Levine and Quick-DASH scores along with a visual analogue score for pain. There were no complications in either group. There was no significant difference in terms of pain or satisfaction. Functional difficulties were greater in the simultaneous group; however, there was no difference in completing simple tasks. Patients reported high satisfaction with either management approach. However, significantly fewer would consider undergoing simultaneous decompression again.

Characterization of an axonemal dynein heavy chain expressed early in airway epithelial ciliogenesis.

The most conspicuous evidence of airway epithelial maturation and vitality is the presence of motile cilia. In an effort to generate genetic and antigenic markers of airway maturation, injury, and repair, we characterized airway epithelial expression of a gene identified by two human expressed sequence tags that encoded peptides with sequence similarity to an invertebrate ciliary dynein heavy chain (DHC). Molecular analyses showed that the gene has a very large RNA transcript that encodes a very high molecular weight polypeptide with biochemical properties that are characteristic of a dynein heavy chain. Expression of the gene transcript correlated with the presence of ciliated cells in tissues, and immunohistochemical localization of the gene product confirmed its presence in the cilia of mature airway epithelium. In epithelium undergoing ciliogenesis ex vivo, expression of the gene transcript preceded ciliation of the epithelium and the gene product was present in the cytoplasm and at the apical border of nonciliated cells. These data suggested that the gene encodes an axonemal DHC that is expressed early during ciliogenesis, before the appearance of cilia.

Computer-assisted analysis of radial symmetry in human airway epithelial cilia: assessment of congenital ciliary defects in primary ciliary dyskinesia.

The ultrastructural analysis of cilia and diagnosis of primary ciliary dyskinesia (PCD) in biopsies of airway epithelium is sometimes confounded by poor sampling, inconsistencies in tissue quality and processing, and other technical problems. Although clinical findings may lead to a presumptive diagnosis, ultrastructural analysis of ciliary axonemes is the standard for confirmation of PCD. The ultrastructural features of the cilium when viewed in cross section by transmission electron microscopy confer a radial symmetry to the axoneme. Current digital image processing techniques can be applied to such images to reinforce signal, diminish noise, and confirm consistency of position of axonemal structures, a process that can augment ultrastructural analysis for PCD. In this study, computer-assisted digital image processing was used to evaluate cross sections of cilia in airway epithelial biopsies from patients previously diagnosed with PCD as well as in control subjects with normal cilia. These studies supported the original diagnoses and provided some new insights into axonemal organization in PCD. This technique is simple and may be useful in providing a supporting means for confirming or ruling out a diagnosis of PCD in cases that appear equivocal.

An autoradiographic assessment of epithelial cell proliferation and post-natal maturation of the tracheal epithelium in infant ferrets.

The tracheal epithelium of infant ferrets undergoes rapid postnatal maturation over the first month of life to achieve the pseudostratified columnar configuration characteristic of the large airways of other mammals. We have used in vivo pulsing with tritiated thymidine ((3)HT) to elicit autoradiographic labeling of cells synthesizing nucleic acids in order to characterize more fully the contribution to development of different cell types comprising the nascent epithelial layer during this period of rapid growth. These studies indicate that two distinct populations of epithelial cells possess proliferative potential and contribute to the establishment of the mature adult epithelial layer. These investigations further confirm the mitotic potential of basal cells during a period of rapid postnatal growth and development of the tracheal epithelial layer. These studies also document the contribution to early airway development by non-ciliated cells, which predominate on the luminal border of the ferret trachea at birth. The temporal and histologic patterns of airway epithelial maturation during post-natal life in the ferret as contained in this study exhibit similarities to those which occur with recovery from injury by infection and irritant exposure in mature airways. Thus, the characterization of epithelial cell compartments having proliferative potential may provide insights into the mechanisms whereby normal airway epithelial organization is established and maintained during development as well as the possible recapitulation of these mechanisms during times of epithelial regeneration following injury.

Connexin 26 expression in human and ferret airways and lung during development.

Coordinated microscopic and molecular biological studies were used to document gap junction expression during postnatal development in ferret tracheal epithelium and lung and in fetal and adult human airway and lung. Expression of connexin 26 (Cx26) in the ferret airways was limited to the epithelial layer and was observed only during the newborn interval. In contrast, we found Cx26 expressed in the alveolar epithelium of the ferret lung by in situ hybridization, Northern blotting, RT-PCR amplification, and immunocytochemical labeling at all ages examined. This finding was further confirmed by documentation of gap junctional plaques upon ultrastructural examination of freeze-fracture replicas of adult ferret lung tissue. Parallel studies of developing human fetal lung and airway suggested connexin expression in the airways only in the first trimester but, as in the ferret, persistent expression was observed in both fetal and adult lung. These studies suggest that the transient expression of Cx26 is a reliable early indicator of airway epithelial development and differentiation in the airways. In contrast, Cx26 expression persists throughout life in the lung, suggesting that gap junctions serve more perennial intercellular communication functions in the peripheral lung.

Variability in distribution and populations of gap junctions in ferret trachea during postnatal development.

Immunocytochemical probes have been used to characterize gap junction distribution in the postnatal ferret trachea by epifluorescence and by laser scanning confocal and electron microscopy. A battery of antibodies directed against fragments of different connexins localized beta 1- and beta 2-gap junction antigens (connexins 32 and 26, respectively) at the intercellular borders of the superficial epithelium while alpha 1-gap junction antigen (connexin 43) was localized to the loose connective tissues. Gap junction labeling in the superficial epithelium declined in the first weeks of life but persisted in the developing submucosal glands to the weanling stage. Localization of the alpha- and beta-antigens was specific for connective tissues and epithelial layers, respectively. These observations suggest that communication competence is an important component of early development in the mammalian airways.

Microtubular discontinuities as acquired ciliary defects in airway epithelium of patients with chronic respiratory diseases.

A critical relationship exists between ordered ciliary ultrastructure and optimal mucociliary clearance in the respiratory airways. Structurally defective cilia derived from heritable syndromes or from epithelial cell injury may promote or exacerbate chronic disease processes. A lesion of airway epithelial cilia characterized by microtubular discontinuities and previously associated with primary ciliary dyskinesia (PCD) has been documented in other forms of chronic airways diseases, including cystic fibrosis (CF). Nasal cilia obtained by curettage of the inferior nasal turbinate from 89 patients without CF but exhibiting symptoms favoring PCD were evaluated by transmission electron microscopy. Of the 89 patients in the study group, 19 (21.4%) were diagnosed with PCD. Among the PCD patients, 16 (84.2%) exhibited microtubular discontinuities. Nine patients from this group without ultrastructural evidence of PCD also exhibited these defects, however. Furthermore, seven of eight nasal biopsy specimens from patients with CF in a separate disease control group exhibited microtubular discontinuities. Microtubular discontinuities were quantitatively negligible among control groups of healthy human subjects and individuals experimentally and naturally subjected to acute airway injury. These data provide evidence that ciliary microtubular discontinuities represent acquired ciliary defects reflective of chronic airway disease injury and are not components of a primary structural abnormality in PCD.

Effect of nitrogen dioxide on human nasal epithelium.

The nasal epithelium of young adult white men in good health was evaluated by electron microscopy in a condition blind fashion relative to exposures of 2 ppm nitrogen dioxide (NO2) or clean air for 4 h. The exposure protocol involved two separate exposures of the same individuals to NO2 or clean air approximately 3 wk apart. We found qualitative and quantitative evidence that luminal border membranes of ciliated cells were ultrastructurally altered in six of seven samples of nasal epithelium obtained following NO2 exposures, although subsequent morphometric statistical analyses were not significant. This alteration was characterized by cilia containing excess matrix in which individual or, more commonly, multiple ciliary axonemes were embedded, and by vesiculations of luminal border ciliary membranes, a pattern less common in clean air-exposed control specimens. Although these patterns were not widespread, their morphology was consistent with findings of previous animal studies involving acute and chronic exposure to NO2. Our findings suggest that adverse effects on mucociliary function in normal humans due to acute exposure to low levels of NO2 are most likely minimal. However, in view of other reports of NO2 exposure in laboratory animals documenting ciliary injury, our observations support a view that similar patterns might appear more prominently with higher NO2 levels and/or more extended exposure intervals.

Nitrogen dioxide exposure and urinary excretion of hydroxyproline and desmosine.

The relationship between average and peak personal exposure to nitrogen dioxide and urinary excretion of hydroxyproline and desmosine was investigated in a population of preschool children and their mothers. Weekly average personal nitrogen dioxide exposures for subjects who resided in homes with one or more potential nitrogen dioxide source (e.g., a kerosene space heater, gas stove, or tobacco smoke) ranged between 16.3 and 50.6 ppb (30.6 and 95.1 micrograms/m3) for children and between 16.9 and 44.1 ppb (12.8 and 82.9 micrograms/m3) for mothers. In these individuals, the hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were unrelated to personal nitrogen dioxide exposure--even though continuous monitoring documented home nitrogen dioxide concentration peaks of 100-475 ppb lasting up to 100 h in duration. Significantly higher hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were observed in children, compared with mothers (p < .001 and .003, respectively).

Otitis media in early childhood and later language.

The relationship between early otitis media with effusion (OME) experience and later language development was examined in a prospective cohort study of 30 children from middle-class families and 33 children from low-income families. Ear status was monitored using otoscopy and tympanometry during wellness and illness periods between birth and 3 years of age. Language was assessed using standardized tests and a language sample between 4 1/2 and 6 years. Findings suggested no reliable relationship between early OME experience and later language development.

Ultrastructure of airway epithelial cell membranes among patients with cystic fibrosis.

Alterations in transepithelial ion fluxes are a primary pathophysiologic feature in cystic fibrosis (CF). Chronic respiratory infections and host responses are secondary aggravating pulmonary complications of this disease. In the present study, the application of the freeze-fracture technique to samples of nasal and tracheal epithelium from patients with CF has provided a perspective of large areas of cell membrane for the evaluation of possible structural correlates to the pathophysiology of this disease. A variety of aberrant configurations in stranding pattern and disorganization of the epithelial tight junctional complexes in CF airway epithelium are described. Additionally, examination of ciliary membranes revealed the presence of compound cilia and dysmorphology of ciliary necklace configuration. These features are thought to represent acquired structural lesions possibly derived from chronic infection and/or host responses which may further exacerbate abnormal ion transport properties and decrements of ciliary function that appear to be associated with the airway epithelium of individuals with CF.

Dynamics of intercellular communication and differentiation in a rapidly developing mammalian airway epithelium.

A considerable body of data suggests that gap junctions represent channels that facilitate intercellular communication, thereby modulating growth and development. However, direct quantitative evidence supporting such a structure/function relationship is limited. This study has identified a new model in the rapidly developing tracheal epithelium of infant ferrets wherein gap junction prevalence and intercellular transfer of a fluorescent, low molecular weight dye, epithelial cell incorporation of tritiated thymidine, and progressive ciliation of the epithelium have been characterized. This developmental pattern provides favorable conditions for the study of relationships between gap junctions, intercellular translocation of chemical signals, and cell growth and differentiation in a mammalian airway epithelium with a minimum of experimental intervention.

Nucleotide sequence of the MgPa (mgp) operon of Mycoplasma genitalium and comparison to the P1 (mpp) operon of Mycoplasma pneumoniae.

The attachment of Mycoplasma genitalium and Mycoplasma pneumoniae to ciliated epithelium involves two surface proteins designated MgPa and P1, respectively. We have previously cloned and sequenced the P1 (mpp) operon of M. pneumoniae, and report here the use of P1-derived probes to clone and sequence a 10.4-kb region of M. genitalium DNA that, by analogy to the P1 operon, contains the MgPa (mgp) operon. The deduced amino acid sequences of the 29-kDa (ORF-1), MgPa (160-kDa) and 114-kDa (ORF-3) proteins of the MgPa operon show extensive homologies with those of the 28-kDa, P1 (170-kDa) and 130-kDa proteins, respectively, encoded by the P1 operon. The common features and homology of these operons are consistent with previous observations that the MgPa and P1 proteins share cross-reactive epitopes, as well as similar biological function. The gene order of the MgPa operon is ORF-1, MgPa, ORF-3, with intervening regions of 6 and 1 nt, respectively. A consensus ribosome-binding site (RBS) sequence is found before ORF-1 and a sequence indicative of a transcription terminator is located beyond ORF-3; the absence of such sequences adjacent to the MgPa gene suggests that the operon is transcribed as a polycistronic message. The RBS sequence is followed by sequences of dyad symmetry that have the potential to form two alternative stem-and-loop structures, which could be involved in controlling initiation of translation.

Otitis media in early childhood and cognitive, academic, and classroom performance of the school-aged child.

The relationship between the occurrence of otitis media during the first 3 years of life and cognitive, academic, and classroom performance during the third year of elementary school was evaluated in 44 socioeconomically disadvantaged children. The children attended a research day-care program where their otitis media experience and psychoeducational development were documented prospectively from birth. No significant relationship was found between otitis media in early childhood and performance on tests of verbal intelligence or academic achievement in the third year of school. The number of days of otitis media before 3 years of age was significantly correlated with teachers' ratings of children's attentional behavior in the classroom, however. Children with more early otitis media tended to be rated as less task oriented and less able to work independently than children with less otitis media. This was an exploratory study of a small number of children. Further study of the potential association is needed.

Development, organization, and function of tight junctional complexes in the tracheal epithelium of infant ferrets.

The surface epithelium of newborn ferret airways matures rapidly in the first month of life. Prominent developmental features include a transition from predominantly non-ciliated to ciliated cells, quantitative and qualitative changes in secretion of macromolecules, and a transition from secretory to absorptive patterns of ion transport. Freeze-fracture replicas of ferret tracheal epithelium from 0 to 28 days of age exhibited progressive developmental patterns in tight junctional structure from beaded, unclosed patterns in newborns to more closed patterns at 28 days. Strand number increased while the depth of tight junctional structures and the proportion of strands exhibiting discontinuity decreased postnatally. Total transepithelial conductance, paracellular conductance, and cell size decreased over the first month. Our data suggest that changes in physiological parameters that reflect epithelial tight junction permeability can be attributed, at least in part, to maturation of this intercellular junction during the postnatal period.

Ciliary defects: cell biology and clinical perspectives.

Considerable progress has been made in achieving a perspective of the pathophysiology of ciliary defects in human disease in the interval between Siewert's and Kartagener's early descriptions of KS. Not only have we achieved a better understanding of some of the mechanisms involved in the pathogenesis of congenital ciliary syndromes, but also we have come to appreciate a new spectrum of ciliary defects, those of acquired etiology. The advent of modern electron microscopy has been a significant element to this progress and its importance is reflected by the numerous studies of ciliary defects that have come in the wake of the pioneering ultrastructural investigations of Afzelius and colleagues. However, each discovery appears to generate additional questions. This is indicative of the importance of the subject to both basic and clinical science and of the vitality of the investigators in this field as a comprehensive understanding of ciliary diseases is sought.