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Biomedical subjects

E D Allen

Publications and source records attributed to E D Allen.

At least 19 recordsLinked to original sources

Induction of interleukin-8 release by lung epithelium with cystic fibrosis epithelial lining fluid is marginally affected by inhibitors of interleukin-1beta.

Interleukin-1beta (IL-1beta) and neutrophil elastase (NE) are present in the epithelial lining fluid (ELF) of patients with cystic fibrosis (CF). Both factors activate surrounding cells including lung epithelial cells, causing release of IL-8, a potent chemoattractant for neutrophils. Previous studies showed up-regulation of IL-8 release by lung epithelial cells as a function of NE in CF; however, few studies addressed the relationship between IL-1beta and activation of lung epithelial cells in CF lungs. Confluent layers of A549 cells, a type II-like human lung epithelial cell line, were incubated overnight with IL-1beta (0-5 ng/ml) or NE (100 nM), and supernatants were analyzed for IL-8 by enzyme-linked immunosorbent assay (ELISA). Both IL-1beta and NE led to a significant increase in IL-8: 12.8 +/- 2.8 ng/ml and 0.8 +/- 0.3 ng/ml, respectively. Next, bronchoalveolar lavage (BAL) samples were obtained from one healthy adult volunteer and six patients with CF and measured for IL-8 and IL-1beta concentrations by ELISA. Both IL-8 (range 169.00 +/- 56.57 to 1742.04 +/- 338.98 pg/ml) and IL-1beta (range 0-24.26 +/- 0.52 pg/ml) were detected in CF specimens, whereas neither was detected in the volunteer's specimen. Normal and CF BALs then were incubated overnight at a 1:10 dilution with confluent A549 cells. Analysis by ELISA of cell-free supernatants revealed increased IL-8 production from cells stimulated with CF BALs only. Similar experiments were performed with BAL supernatants that had been incubated with soluble IL-1 type II receptor, soluble IL-1 receptor antagonist, or a peptide inhibitor of NE. Addition of IL-1 inhibitors had a marginal effect on the amount of IL-8 release after incubation with CF BAL samples, whereas inhibition of NE had no effect. Our results indicate that other factors present in ELF in CF account for IL-8 release from lung epithelial cells.

Adolescent↗

Correlation between early, measurable improvement in quality of life and speed of visual rehabilitation after phacoemulsification.

PURPOSE: To assess whether improvements in measurable health-related quality-of-life (HR-QoL) functions parallel the rapid visual recovery after phacoemulsification. SETTING: The Cataract Treatment Center, Sunderland Eye Infirmary, Sunderland, England. METHODS: This study comprised 144 patients having first-eye phacoemulsification cataract extraction. They were assessed using a standard EuroQoL generic (non-disease specific) multidimensional HR-QoL instrument to evaluate preoperative and 1 month postoperative health profile measures in social, psychological, and general health aspects. RESULTS: Within 1 month of phacoemulsification, change in vision was accompanied by significant changes in HR-QoL functions such as home activities, social activities, self-care, mobility, and psychological well-being. CONCLUSION: The speed of visual rehabilitation after phacoemulsification was paralleled by improvement across HR-QoL functions, resulting in the rapid recovery of functional independence and health status.

Adult↗

Cystic fibrosis: a decade of progress.

Cystic fibrosis (CF) is an autosomal recessive, multisystem disorder which greatly reduces the lifespan of its victims, largely by gradual, infection-driven destruction of the lungs. Advances in therapy to date have improved median survival from less than 10 years to over 30 years of age. New scientific advances in the past 10 years, notably discovery of the CF gene and increasing understanding of its protein product, hold forth hope of even further therapeutic advances. This review will highlight the clinical characteristics of CF, current standard therapies and directions of ongoing research.

Journal Article↗

Role of the plasminogen activator and matrix metalloproteinase systems in epidermal growth factor- and scatter factor-stimulated invasion of carcinoma cells.

Normal as well as neoplastic cells traverse extracellular matrix barriers by mobilizing proteolytic enzymes in response to epidermal growth factor (EGF)-EGF receptor (EGFR) or hepatocyte growth factor/scatter factor (SF)-c-Met interactions. The plasminogen activator-plasminogen axis has been proposed to play a key role during cell invasion, but the normal development of plasminogen activator- as well as that of plasminogen-deficient mice supports the existence of alternate proteolytic systems that permit cells to traverse extracellular matrix barriers. To characterize the role that matrix-degrading proteinases play in EGF- or SF-stimulated invasion, a human squamous carcinoma cell line (UM-SCC-1) was triggered atop the matrices of type I collagen or human dermal explants in a three-dimensional culture system. During EGF- or SF-induced invasion, UM-SCC-1 cells expressed urokinase-type plasminogen activator (uPA) and uPA receptor as well as the matrix metalloproteinases (MMPs), membrane-type MMP-1, collagenase 1, stromelysin 1, and gelatinase B. Despite the presence of a positive correlation between uPA receptor-uPA expression and growth factor-stimulated invasion, UM-SCC-1 invasion was not affected by inhibitors directed against the plasminogen activator-plasminogen axis. In contrast, both recombinant and synthetic MMP inhibitors completely suppressed invasion by either EGF- or SF-stimulated cells without affecting either proteinase expression or cell motility across collagen-coated surfaces. These data demonstrate that MMPs, but not the plasminogen activator-plasmin system, can directly regulate the ability of either EGF- or SF-stimulated tumor cells to invade interstitial matrix barriers.

Animals↗

Contrast sensitivity after implantation of diffractive bifocal and monofocal intraocular lenses.

PURPOSE: To compare contrast sensitivity (CS) after implantation of a diffractive bifocal intraocular lens (IOL) and a monofocal IOL of similar design. SETTING: Seven European centers. METHODS: In this randomized, prospective study, CS was tested 5 months after cataract and IOL implantation surgery in 115 patients with a diffractive bifocal IOL and 106 patients with a monofocal IOL. It was also tested in a subgroup of 38 patients who had bilateral implantation of a diffractive bifocal IOL. Contrast sensitivity was tested using the Vision Contrast Test System (VCTS). RESULTS: In patients with a best corrected visual acuity (BCVA) of 1.0 or better, the CS at all spatial frequencies (1.5 to 18 cycles/degree), both at distance and near, was slightly lower in the bifocal IOL group than in the monofocal group. Mean values were within the normal range. In patients with a BCVA of less than 1.0, the CS was lower and the difference between the bifocal and monofocal groups was less. In patients with bilateral bifocal IOLs, CS was better when tested bilaterally than when testing the better eye alone. Pupil size affected the results to a small degree. Contrast sensitivity appeared to improve over time after implantation of a diffractive bifocal IOL. CONCLUSIONS: In patients with cataract and no other eye pathology, the diffractive bifocal IOL with slightly reduce the CS at all spatial frequencies. In those with reduced visual acuity after cataract surgery, CS will be reduced accordingly. In this situation, the reduction from the diffractive bifocal optic would be minor.

Aged↗

Six-week trial of nebulized flunisolide nasal spray: efficacy in young children with moderately severe asthma.

This study evaluated the clinical efficacy of nebulized flunisolide nasal solution (Nasalide) in young children with moderately severe asthma. Twenty-two asthmatic children, ages 12-72 months, completed this double-blind placebo-controlled study. After a 6-week observation period, 18 patients were paired according to asthma severity. One child from each pair was randomized to flunisolide, the other to placebo; 4 patients were independently randomized. Placebo or drug was then administered for 6 weeks. Throughout the study, symptoms, drug usage, and analog scales reflecting asthma severity and family disruption were recorded in a diary. Multiple regression analysis was used to compare the flunisolide and placebo groups in regard to the amount of improvement demonstrated from the observation to the active periods of the study. Analog scores of asthma severity and family disruption, albuterol aerosol use, and systemic corticosteroid use fell roughly 40% from baseline in the flunisolide group. This improvement was significant compared to the placebo group. We conclude that 1 ml (250 microg) of nebulized flunisolide nasal spray solution, administered three times daily, reduced the severity of asthma symptoms, and the need for both albuterol aerosol and systemic corticosteroid therapy in young children with moderately severe asthma during a 6-week trial. Longer term studies are warranted.

Administration, Intranasal↗

Detection of IL-5 and IL-1 receptor antagonist in bronchoalveolar lavage fluid in acute eosinophilic pneumonia.

BACKGROUND: Acute eosinophilic pneumonia is an idiopathic cause of respiratory failure, characterized by very high numbers of alveolar eosinophils without significant blood eosinophilia. OBJECTIVE: The purpose of this study was to determine which cytokines are associated with acute eosinophilic pneumonia. METHODS: Soluble IL-1 type II receptor and the cytokines IL-1 beta, IL-1ra, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha were measured in serum and in bronchoalveolar lavage fluid from two patients with acute eosinophilic pneumonia during both acute and convalescent phases. RESULTS: Compared with patients with adult respiratory distress syndrome, the patients with acute eosinophilic pneumonia had high bronchoalveolar lavage fluid levels of IL-5, IL-1ra, and soluble type II IL-1 receptor but not IL-1 beta, tumor necrosis factor-alpha, IL-3, or granulocyte-macrophage colony-stimulating factor. Bronchoalveolar lavage fluid levels of IL-5 and IL-1ra fell after resolution of symptoms. In the serum of patients with acute eosinophilic pneumonia, IL-5 was not detectable, and IL-1ra was initially high but fell after corticosteroid treatment. CONCLUSION: Acute eosinophilic pneumonia is characterized by locally high levels of IL-5, IL-1ra, and soluble type II IL-1 receptor in the alveolar space.

Acute Disease↗

Comparison of a diffractive bifocal and a monofocal intraocular lens.

PURPOSE: To compare a Pharmacia diffractive bifocal intraocular lens (IOL) with a monofocal lens of the same design without the diffractive grating. SETTING: Multicenter study. METHODS: This randomized, prospective study comprised 70 patients with a monofocal IOL and 79 with a diffractive bifocal IOL. Follow-up was 5 to 6 months. Near and distance visual acuities, contract sensitivity, patient satisfaction, and spectacle use were evaluated. RESULTS: All patients achieved a best corrected visual acuity of 0.5 or better; 80% in the monofocal and 71% in the bifocal group had a best corrected visual acuity of 1.0 or better. Without correction, 93% of the bifocal and 9% of the monofocal group could read J3 or better. With distance correction, 99% and 4%, respectively, could read J3 or better. Contrast sensitivity was slightly lower in the bifocal group at distance and near for all spatial frequencies. In the bifocal group, 46% never used spectacles for near tasks. Overall satisfaction was rated good by 86% of the monofocal and 85% of the bifocal group. CONCLUSIONS: The diffractive bifocal IOL performed well at distance and near. Patients who no longer require spectacles will benefit significantly from a bifocal IOL, but many with a bifocal IOL in one eye will require spectacles for the fellow eye.

Aged↗

Cost effectiveness of a single-function treatment center for cataract surgery.

PURPOSE: To compare the clinical and cost effectiveness of two models for cataract treatment: a single-function Cataract Treatment Centre (CTC) and a general ophthalmology service. SETTING: Cataract Treatment Centre and the general ophthalmology service at Sunderland Eye Infirmary, Sunderland, United Kingdom. METHODS: Two hundred patients were studied using two models of care: 100 in the CTC and 100 in the general ophthalmology service. Outcome measures were best corrected visual at 3 months postoperatively or at discharge and occurrence of surgery-related complications. All direct costs to the National Health Service were identified, measure, and assessed. RESULTS: Clinical outcomes in the two groups were similar. The average cost per patient was 496.90 pounds ($760.25) at the CTC and 566.34 pounds ($866.50) at the general ophthalmology service. The cost per patient treated as a day case in the general service group was 495.84 pounds ($758.63). Thus, treatment at the CTC was more cost effective than in the mixed service group and as cost effective as in the day case subgroup. CONCLUSIONS: Depending on local circumstances, day care must be delivered more cost effectively in a single-function center than in a general ophthalmology service. We recommend day care using local anesthesia and protocols for assessment, surgery, and follow-up.

Anesthesia↗

Acute eosinophilic pneumonia. A summary of 15 cases and review of the literature.

Idiopathic acute eosinophilic pneumonia (AEP) is an acute febrile illness that may be mistaken for an infectious pneumonia. Patients are often young and otherwise healthy. Clues to considering this disorder in a differential diagnosis include the acuity and severity of the clinical presentation and an initial chest X-ray with diffuse infiltrates, often interstitial, and the presence of Kerley B lines and/or evidence of pleural fluid. The diagnosis can be made through examination of bronchoalveolar lavage fluid in most cases, with careful exclusion of other similar eosinophilic lung disease. Although it can lead to life-threatening respiratory failure, AEP is easily treatable with corticosteroids. This disease has not been reported to recur in any patients to this point.

Acute Disease↗

Opportunities for the use of aerosolized alpha 1-antitrypsin for the treatment of cystic fibrosis.

Cystic fibrosis (CF), the most common lethal genetic disease affecting the white population, owes its morbidity and mortality primarily to the devastating effects of chronic inflammation and infection within the pulmonary airways. It has become increasingly recognized that the host's response to Pseudomonas species and Staphylococcus aureus infection plays a paramount role in CF lung destruction and eventual development of respiratory insufficiency. A massive pulmonary influx of neutrophils, and accompanying excessive levels of neutrophil elastase (NE), can be detected in the bronchoalveolar fluid of even very young children with CF. The excess of NE adversely affects the CF airways by enhancing mucus secretion, directly injuring airway tissues, exacerbating the inflammatory process by attracting more neutrophils, and derailing opsonization and elimination of bacterial pathogens, particularly Pseudomonas aeruginosa. Neutralization of excess NE by delivering supplemental alpha 1-antitrypsin to the airways via aerosolization represents an exciting new potential therapy for CF lung disease.

Aerosols↗

Functional residual capacity (FRC) measurements by plethysmography and helium dilution in normal infants.

Comparative measurements of functional residual capacity (FRC) made by plethysmography (FRCpleth) and by helium dilution (FRCHe) were obtained on 27 infants and young children without known pulmonary disease (14 males, 13 females; 4 weeks-26 months; mean age 32.2 weeks) while under chloral hydrate sedation. Clinical histories, clinical examinations, and pulmonary functions were normal for all members of the group. FRCpleth, whether measured near end expiration (EE) or near end inspiration (EI), and corrected to mean expiratory levels of at least 3 breathing cycles, was consistently and significantly greater than FRCHe. Comparative values for mean (+/- standard deviation) were FRCpleth EE, 182.0 (+/- 79.7) mL and FRCpleth El, 171.8 (+/- 77.4) mL vs. FRCHe, 154 (+/- 72.2) mL, P < 0.0001 and P < 0.005, respectively. Normalizing values by weight, FRCpleth EE was 23.8 mL/kg (+/- 5.3) vs. FRCHe, 20.2 (+/- 4.7) mL/kg, mean (+/- standard deviation). The difference between FRCpleth and FRCHe, expressed as FRCpleth - FRCHe/FRCpleth x 100, was 9% for occlusions at end inspiration and 16% for occlusions at end expiration. The following equations describe our FRC results in relation to length: In (FRCHe) = 2.74 x ln (length) - 6.53 r2 = 0.781 slope = 2.74 +/- 0.29 SE Y intercept = 6.53 +/- 1.12 SE ln (FRCPleth EI) = 2.69 x ln (length) - 6.21 r2 = 0.752 slope = 2.69 +/- 0.31 SE Y intercept = 6.21 +/- 1.29 SE The difference between FRCpleth and FRCHe was more marked when occlusions were performed at end expiration than at end inspiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

MR and CT imaging patterns in post-varicella encephalitis.

The aim of the investigation was to determine the patterns of cerebral involvement on computed tomography (CT) and magnetic resonance (MR) imaging in post-varicella encephalitis. Four children between the ages of 2 and 11 years presented over a 5-year period with a diagnosis of post-varicella encephalitis. Their imaging studies and clinical data were reviewed retrospectively. The medical histories of all four children were noncontributory except for recent bouts of chickenpox 1 week to 3 months prior to hospitalization. Three children presented with parkinsonian manifestations. Bilateral, symmetric hypodense, nonenhancing basal ganglia lesions were found on CT. These areas showed nonenhancing low signal intensity on T1-weighted images and high signal intensity on T2-weighted images on MR. One child presented with diffuse, multiple gray and white matter lesions of similar imaging characteristics; some lesions, however, did enhance. This child had no gait disturbances. Post-varicella encephalitis can produce two patterns of dramatic CT and MR findings. With an appropriate history and clinical findings, varicella as a cause of bilateral basal ganglia or diffuse cerebral lesions can be differentiated from other possible etiologies which include trauma, anoxia, metabolic disorders and demyelinating diseases.

Chickenpox↗

Prolonged parenteral nutrition for cystic fibrosis patients.

To evaluate the clinical impact of prolonged parenteral nutritional (PN) therapy on patients with advanced cystic fibrosis, we conducted a retrospective chart review of 25 cystic fibrosis patients who underwent prolonged PN (median course 295 days) at our institution between August 1988 and May 1992. The patients' survival status, change in percentage of ideal body weight, need for ongoing nutritional intervention, pulmonary function test changes, i.v. antibiotic use, and complication rates were assessed. Patients gained significant weight while receiving PN, but they lost weight when PN was discontinued. PN did not clearly improve pulmonary status. IV antibiotic therapy nearly doubled during PN. Central venous catheter sepsis rates rose from 1.29 to 3.45 per 1000 catheter days during PN therapy. In conclusion, prolonged PN promotes weight gain in cystic fibrosis patients with severe disease; however, the effect is transient and involves a significantly increased risk of sepsis.

Adolescent↗

Structural and functional changes in salivary glands during aging.

Various salivary glands in senescent humans and other animals have been examined extensively to characterize the structural and functional changes that occur during aging. Although a wide range of different structural changes, involving both the parenchymal and stromal tissues, have been described, it is unclear how any of these changes affects the function of the salivary glands. One major change in structure is the reduction in the volume of acini with a concomitant increase in the ductal volume. Despite this loss of functional acini, the salivary output and the contents seem to be unaltered, or minimally altered, due to aging. One consistent change observed in many salivary glands of aged animals is the decline in the rate of synthesis of proteins and their messenger RNA (mRNA). However, the salivary acinar cells from aged animals can synthesize secretory proteins at an elevated rate just as effectively as those from their younger counterparts in response to external stimuli, which are known to enhance the rate of protein synthesis. Thus, it appears that the salivary acinar cells, which remain structurally intact during aging, seem to retain their functional efficiency. Furthermore, these acinar cells, although reduced in number, are sufficient in quantity to carry out most of the salivary gland functions.

Aging↗

Orbital cellulitis--an unusual presentation and late complication of severe facial trauma.

We report an unusual case of orbital cellulitis in a patient with only one seeing eye and severe facial asymmetry secondary to a road traffic accident twenty two years previously. Facial trauma sustained in the road traffic accident created continuity between the right orbit and the adjacent ethmoidal cells. The abnormal communication between the ethmoidal labyrinth and the right orbit rendered this patient highly susceptible to an orbital cellulitis from an adjacent paranasal sinus infection. However, this case is unusual with regard to the length of time that elapsed before such an infection became manifest and the presence of gross distortion of anatomy masked the usual presentation and thereby caused a delay in diagnosis.

Accidents, Traffic↗