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Biomedical subjects

J L Carson

Publications and source records attributed to J L Carson.

At least 91 records · Page 5Linked to original sources

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.

Adolescent↗

The epidemiology of the acute flank pain syndrome from suprofen.

Suprofen, a new nonsteroidal anti-inflammatory drug, was marketed in early 1986 as an analgesic agent. Until physicians began reporting an unusual acute flank pain syndrome to the spontaneous reporting system, 700,000 persons used the drug in the United States. Through August 1986, a total of 163 cases of this syndrome were reported. To elucidate the epidemiology of the syndrome, a case-control study was performed, comparing 62 of the case patients who had been reported to the spontaneous reporting system to 185 suprofen-exposed control subjects who did not have the syndrome. Case patients were more likely to be men (odds ratio, 3.8; 95% confidence interval, 1.2-12.1), suffer from hay fever and asthma (odds ratio, 3.4; 95% confidence interval, 1.0-11.9); to participate in regular exercise (odds ratio, 5.9; 95% confidence interval, 1.1-30.7), especially in the use of Nautilus equipment (p = 0.02); and to use alcohol (odds ratio, 4.4; 95% confidence interval, 1.1-17.5). Possible risk factors included young age, concurrent use of other analgesic agents (especially ibuprofen), preexisting renal disease, a history of kidney stones, a history of gout, a recent increase in activity, a recent increase in sun exposure, and residence in the Sunbelt. These were findings that were suggestive but did not reach conventional statistical significance. These findings are consistent with the postulated mechanism for this unusual syndrome: acute diffuse crystallization of uric acid in renal tubules.

Acute Kidney Injury↗

Pseudomonas pellicle in disinfectant testing: electron microscopy, pellicle removal, and effect on test results.

Pseudomonas aeruginosa ATCC 15442 is a required organism in the Association of Official Analytical Chemists use-dilution method for disinfectant efficacy testing. When grown in a liquid medium, P. aeruginosa produces a dense mat or pellicle at the broth/air interface. The purpose of this investigation was to examine the pellicle by scanning electron microscopy, to evaluate three pellicle removal methods, and to determine the effect of pellicle fragments on disinfectant efficacy test results. The efficacies of three methods of pellicle removal (decanting, vacuum suction, and filtration) were assessed by quantifying cell numbers on penicylinders. The Association of Official Analytical Chemists use-dilution method was used to determine whether pellicle fragments in the tubes used to inoculate penicylinders affected test results. Scanning electron micrographs showed the pellicle to be a dense mass of intact, interlacing cells at least 10 microns thick. No significant differences in pellicle removal methods were observed, and the presence of pellicle fragments usually increased the number of positive tubes in the use-dilution method significantly.

Disinfectants↗

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.

Animals↗

Severity of anaemia and operative mortality and morbidity.

In a case-control study of 125 surgical patients who declined blood transfusions for religious reasons operative mortality was inversely related to the preoperative haemoglobin level, rising from 7.1% for patients with levels above 10 g/dl to 61.5% for those with levels below 6 g/dl. Mortality rates were also related to blood loss during surgery, rising from 8% for patients who lost less than 500 ml to 42.9% for those who lost more than 2000 ml. Both preoperative haemoglobin level and operative blood loss should be considered in assessing the need for preoperative transfusion. In our study no patient with a haemoglobin level above 8 g/dl and operative blood loss below 500 ml died.

Analysis of Variance↗

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.

Animals↗

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.

Adult↗

A case study: nonsteroidal antiinflammatory drugs and gastrointestinal bleeding.

This paper describes a postmarketing drug surveillance study which examined the association of upper gastrointestinal (GI) bleeding and exposure to nonsteroidal antiinflammatory drugs (NSAID). The rate of upper GI bleeding was compared in 47,136 patients exposed to a NSAID and 44,634 unexposed patients. The risk of bleeding was 1.5 times higher in patients exposed to a NSAID (95% confidence interval, 1.2-2.0). Dose (p less than 0.01) and duration (p less than 0.001) response relationships were identified. The rate of upper GI bleeding was then compared among 88,044 patients exposed to only one NSAID. Sulindac was associated with the highest rate of upper GI bleeding. Control for multiple potential confounding variables did not change the results. These results suggest that NSAID are associated with upper GI bleeding, and that sulindac may lead to upper GI bleeding more frequently than other NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗

The effect of indication on the risk of hypersensitivity reactions associated with tolmetin sodium vs other nonsteroidal antiinflammatory drugs.

A retrospective cohort study using 1980-1984 Medicaid billing data from 3 US states was performed to assess the relative risk of hypersensitivity reactions from different nonsteroidal antiinflammatory drugs (NSAID). Comparing tolmetin sodium to other NSAID, pooling the data across the 3 US states using the Mantel-Haenszel procedure, gave an overall relative risk (95% confidence interval) of 1.1 (0.8-1.4). After adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.9 (0.6-1.2) was observed. These data do not confirm previous suggestions that use of tolmetin is associated with a higher risk of hypersensitivity reactions than use of other NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗

The effect of indication on hypersensitivity reactions associated with zomepirac sodium and other nonsteroidal antiinflammatory drugs.

A large, computerized database derived from Medicaid claims was used to evaluate the risk of allergy and/or anaphylaxis associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) as a class and the risk associated with the use of zomepirac relative to other NSAIDs. We compared 51,797 patients exposed to NSAIDs with 35,634 age- and sex-matched patients who had not been exposed. As a class, NSAIDs were associated with an adjusted relative risk (95% confidence interval) of hypersensitivity reactions of 2.0 (1.3-2.9). The increased risk was accentuated in those with a diagnosis compatible with acute pain (3.6 [2.2-5.9]) and absent in those without such a diagnosis (1.1 [0.6-1.9]). Comparison of those exposed to zomepirac with those exposed to other NSAIDs resulted in an age-adjusted relative risk of 2.0 (1.1-4.7). Stratification by the probable indication for NSAID use again suggested that the risk may be explained by the use of the NSAIDs for different indications. We concluded that NSAIDs are associated with an increased risk of allergy and/or anaphylaxis, and the use of zomepirac appears to be associated with an increased risk compared with the use of other NSAIDs. However, that increased risk may be a function of the primary indication for the drug or, more likely, the regimen associated with that indication, rather than an intrinsic property of the drug.

Adult↗

The appearance of compound cilia in the nasal mucosa of normal human subjects following acute, in vivo exposure to sulfur dioxide.

Electron microscopic examination of ultrathin sections of ciliated nasal epithelium obtained from seven normal, healthy human volunteers indicated increases in the prevalence of compound cilia following controlled, acute exposure to 0.75 ppm sulfur dioxide (SO2). Morphometric analyses of the specimens confirmed a statistically significant association between SO2 exposure and compounding of nasal epithelial cilia in four of the seven subjects. Concomitant freeze-fracture replicas prepared from these samples also revealed the occurrence of compound cilia with accompanying evidence of abnormal ciliary membrane ultrastructure in the nasal epithelium. These studies indicate that SO2 may be implicated as a causative agent in ciliary compounding in the upper respiratory tract and that compound cilia represent a form of acquired ciliary defect which may serve as a readily quantifiable marker of epithelial injury.

Cilia↗

Features of developing ferret tracheal epithelium: ultrastructural observations of in vivo and in vitro differentiation of ciliated cells.

Ultrastructural features of the developing, surface epithelium of ferrets from birth to 28 days of age were characterized. Progressive ciliogenesis in vivo was observed, beginning with cells covering the membranous portion of the trachea. Emerging cilia appeared in ultrathin sections and by scanning electron microscopy at sites correlating with accumulation of integral membrane particles seen in freeze-fracture preparations. Two patterns of ciliogenesis were observed: (1) the random emergence of cilia over the apical cell surface, and (2) initial emergence of cilia at the peripheral boundary of the luminal border of individual cells. Novel, ringlike structures were observed on the surfaces of nonciliated cells at all ages studied. Active ciliogenesis as well as the appearance of ring structures also were documented in the superficial epithelium from 1- to 5-day-old animals maintained in vitro for up to 4 days.

Aging↗

The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding.

To evaluate the risk of developing upper gastrointestinal (UGI) bleeding from nonsteroidal anti-inflammatory drugs (NSAIDs), a retrospective (historical) cohort study was performed, using a computerized data base including 1980 billing data from all Medicaid patients in the states of Michigan and Minnesota. Comparing 47,136 exposed patients to 44,634 unexposed patients, the unadjusted relative risk for developing UGI bleeding 30 days after exposure to a NSAID was 1.5 (95% confidence interval 1.2 to 2.0). Univariate analyses demonstrated associations between UGI bleeding and age, sex, state, alcohol-related diagnoses, preexisting abdominal conditions, and use of anticoagulants. This association between NSAIDs and UGI bleeding was unchanged after adjusting for these potential confounding variables using logistic regression. A linear dose-response relationship and a quadratic duration-response relationship were demonstrated. Non-steroidal anti-inflammatory drugs are associated with UGI bleeding, although the magnitude of the increased risk is reassuringly small.

Anti-Inflammatory Agents, Non-Steroidal↗

Upper gastrointestinal tract bleeding from oral potassium chloride. Comparative risk from microencapsulated vs wax-matrix formulations.

A retrospective cohort study was performed to assess the relative risk of upper gastrointestinal (UGI) tract bleeding from two formulations of potassium chloride. Relevant information was obtained from 1980 through 1984 Medicaid billing data from the states of Michigan, Minnesota, Florida, and Ohio. After patients with a history of UGI tract bleeding prior to their first prescription for either of the two potassium chloride preparations under study were excluded, data were analyzed for 28,790 patients (143,512 patient-months) dispensed a microencapsulated formulation exclusively and 76,118 patients (560,341 patient-months) dispensed a wax-matrix formulation exclusively. The risk of UGI tract bleeding within 30 days after each prescription for the drug of interest was examined. After sampling from the undiseased study subjects and adjusting for multiple potential confounding variables using logistic regression, an odds ratio (95% confidence interval) of 0.67 (0.52 to 0.85) was observed.

Administration, Oral↗