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Biomedical subjects

K R Young

Publications and source records attributed to K R Young.

At least 19 recordsLinked to original sources
PubMed2001

A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis.

Immunologic reactivity to lipid-DNA conjugates has traditionally been viewed as less of an issue than with viral vectors. We performed a dose escalation safety trial of aerosolized cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the lower airways of eight adult cystic fibrosis patients, and monitored expression by RT-PCR. The cDNA was complexed to a cationic lipid amphiphile (GL-67) consisting of a cholesterol anchor linked to a spermine head group. CFTR transgene was detected in three patients at 2-7 days after gene administration. Four of the eight patients developed a pronounced clinical syndrome of fever (maximum of 103.3EF), myalgias, and arthralgia beginning within 6 hr of gene administration. Serum IL-6 but not levels of IL-8, IL-1, TNF-alpha, or IFN-gamma became elevated within 1-3 hr of gene administration. No antibodies to the cationic liposome or plasmid DNA were detected. We found that plasmid DNA by itself elicited minimal proliferation of peripheral blood mononuclear cells taken from study patients, but led to brisk immune cell proliferation when complexed to a cationic lipid. Lipid and DNA were synergistic in causing this response. Cellular proliferation was also seen with eukaryotic DNA, suggesting that at least part of the immunologic response to lipid-DNA conjugates is independent of unmethylated (E. coli-derived) CpG sequences that have previously been associated with innate inflammatory changes in the lung.

Administration, Inhalation↗
PubMed2001

Management of congenital abnormalities of the donor lung.

Congenital abnormalities were encountered in three donor lungs. A donor tracheal bronchus was incorporated into the right bronchial anastomosis. Anomalous pulmonary venous return of the right upper lobe to the superior vena cava and the left upper lobe to the innominate vein were managed by bridging the anomalous veins to the left atrial cuff with autologous pericardium and donor iliac vein, respectively.

Bronchi↗
PubMed2001

Association of reactive nitrogen species metabolites, myeloperoxidase, and airway inflammation in lung transplants.

BACKGROUND: We have previously reported that patients who had single or double lung transplants had higher concentrations than controls of nitrite and nitrate, which are metabolites of reactive nitrogen species (RNS), in bronchoalveolar lavage fluid (BALF) and serum. METHODS: This study investigates implications of RNS metabolites as markers of airway inflammation in a distinct group of lung transplant patients (n = 40). All patients underwent spirometry, routine surveillance transbronchial lung biopsies, and bronchoalveolar lavage as required by clinical protocol. Four normal controls also had bronchoscopy for measurement of BALF nitrite (NO2-) and nitrate (NO3-). BALF NO2- and NO3-, myeloperoxidase (MPO), protein, and urea were assayed. Total nitrite (NO2- plus enzymatically reduced NO3-) and urea were measured in serum. RESULTS: BALF RNS metabolites were mainly NO3-. Forced expiratory volume in 1 s (FEV1) obtained near bronchoscopy was compared with best postoperative FEV1. Total nitrite in transplant patients' BALF and serum were 3.8 +/- 0.2 and 49 +/- 5 microM, respectively. Total nitrite in controls' BALF and serum were 2.2 +/- 0.7 and 19 +/- 2 microM, respectively (P < 0.05 compared with transplant values). Serum total nitrite correlated (Pearson product moment) with percentage of neutrophils in BALF (R = 0.650, P < 0.0001), MPO (R = 0.431, P = 0.0055), change in FEV1 from baseline (deltaFEV1) (R = -0348, P = 0.0298), and days after transplantation (R = 0.345, P = 0.0294). None of the associated variables, airway inflanmmation (quantified as a score, "B"), deltaFEV1, serum, or BALF total nitrite, were explained by infection. Univariate analysis of airway inflammation in patients showed that it was associated with BALF neutrophils, deltaFEV1, and serum total nitrite. CONCLUSIONS: Serum nitrite appears to reflect the degree of airway inflammation in this lung-transplant study group.

Adult↗
PubMed2000

The utility of open lung biopsy following lung transplantation.

BACKGROUND: Most pulmonary complications associated with lung transplantation have non-specific clinical characteristics. Furthermore, common diagnostic modalities, including bronchoscopy with transbronchial biopsy (TBB), often do not render a definitive diagnosis. In this study, we reviewed our experience with open lung biopsy (OLB) following lung transplantation, specifically regarding its ability to safely provide clinically relevant information that affects therapeutic decisions. METHODS: From October 1989 to March 2000, 202 patients underwent lung transplantation at our institution. We reviewed the clinical course of the 42 patients who received 48 OLBs. Of these patients, we determined the pre-operative clinical condition, preceding TBB histologic information, OLB histology, treatment changes, and procedural complications as a result of the OLB. RESULTS: A new, clinically unsuspected diagnosis was made in 14 biopsies (29% of all OLB), and all of these resulted in therapy changes. Thirty-two biopsies (67% of all OLB) confirmed our clinical suspicions, and new therapy was initiated in 30 of these patients. Two patients (4% of all OLB) had non-diagnostic OLB. Four biopsies (8% of all OLB), including the 2 non-diagnostic OLBs, did not result in any therapy changes or initiation of new therapy. Complications occurred in 3 patients, all of whom had an air leak for >7 days. CONCLUSION: Open lung biopsy in lung transplant patients renders a new, unsuspected diagnosis in nearly one third of patients and leads to specific, directed therapy in the vast majority of patients. Open-lung biopsy can be performed safely and should be considered when diagnosis is uncertain in clinically deteriorating patients.

Biopsy↗
PubMed1999

Recurrence of bronchioloalveolar carcinoma in transplanted lungs.

BACKGROUND: Bronchioloalveolar carcinoma is a distinctive subtype of typical adenocarcinoma of the lung that tends to metastasize widely throughout the lungs but less commonly elsewhere. Because conventional therapies for intrapulmonary metastatic bronchioloalveolar carcinoma are generally ineffective, we treated seven patients who had intrapulmonary metastatic bronchioloalveolar carcinoma with lung transplantation. METHODS: Seven patients with biopsy-proved bronchioloalveolar carcinoma and no evidence of extrapulmonary disease received transplants of either one or two cadaveric lungs. At transplantation, all native lung tissue was removed and replaced with a donor lung or lungs. The patients received the usual post-transplantation care given at the institution. RESULTS: Four of the seven patients had recurrent bronchioloalveolar carcinoma within the donor lungs; the recurrences appeared from 10 to 48 months after transplantation. All recurrences were limited to the donor lungs. Histologic and molecular analyses showed that the recurrent tumors in three patients originated from the recipients of the transplants. CONCLUSIONS: Lung transplantation for bronchioloalveolar carcinoma is technically feasible, but recurrence of the original tumor within the donor lungs up to four years after transplantation was common.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1998

Pulmonary manifestations of Goodpasture's syndrome. Antiglomerular basement membrane disease and related disorders.

Goodpasture's syndrome, or antiglomerular basement membrane disease, is a disorder in which lungs and kidneys are affected by the binding of anti-GBM antibodies, leading to pulmonary hemorrhage and glomerulonephritis with rapidly progressive renal insufficiency. Recent advances in the understanding of disease pathogenesis and diagnosis and treatment have significantly improved our ability to recognize the syndrome, distinguish it from other similar disorders, and offer successful treatment. This article focuses on the pathogenetic features, clinical manifestations, diagnostic strategies, and therapeutic principles of anti-GBM disease.

Anti-Glomerular Basement Membrane Disease↗
PubMed1998

Can chest CT decrease the use of preoperative bronchoscopy in the evaluation of suspected bronchogenic carcinoma?

BACKGROUND: Fiberoptic bronchoscopy (FOB) is frequently used to diagnose and stage bronchogenic carcinoma (BC). However, the value of FOB in diagnosis/staging BC presenting as a pulmonary nodule or mass (PNM) is controversial. Since chest CT is usually obtained in these patients, it may be used in patient selection for preoperative FOB. OBJECTIVE: Evaluation of the role of chest CT in determining the predictive value of FOB in diagnosing/staging a PNM, by comparing the results of CT and bronchoscopy. DESIGN: Retrospective review of chest CTs and medical records. PATIENTS: Consecutive patients with BC between 1992 and 1994 who had diagnostic FOB and CT in our institution, but without radiographic evidence of (1) pulmonary atelectasis, (2) endobronchial tumor or narrowing of the central airways, and (3) the PNM abutting the central airways. RESULTS: Sixty-four patients met the selection criteria. The size of the PNM ranged from 1.5 to 10 cm; the size was < or = 4 cm in 62 patients. FOB provided a diagnosis in 22 patients. Bronchoscopy detected endobronchial lesions in 11 patients (17%); 3 had lesions in more than one lobe. In three patients, the PNM was <3 cm. The radiographically undetected endobronchial tumor increased the tumor stage in only two patients. The "CT bronchus" sign had a positive and negative predictive value of 75% and 68%, respectively. CONCLUSIONS: (1) In this study, CT failed to detect endobronchial tumor in 11 of 64 patients (17%). Because of the implications of a new staging system, more studies are necessary before abandoning staging FOB. (2) The CT bronchus sign has a very high positive and negative predictive value in the use of diagnostic FOB and should be used to guide the method of biopsy of a PNM.

Bronchoscopes↗
PubMed1995

Determining the collateral effects of peer tutor training on a student with severe disabilities.

In one experiment and two case studies, we evaluated the impact of training peer tutors without disabilities to provide effective instructional procedures with a student with severe disabilities who exhibited aberrant behaviors in the classroom. Peer tutors received training on how to provide appropriate commands and specific praise statements, as well as to decrease negative statements. In the experiment, two peer tutors were taught these skills in a multiple baseline design. Two case studies further clarified the impact of the peer tutor training. In Case Study 1, one peer tutor received training on the three skills concurrently and data were assessed in an AB design. In Case Study 2, one peer tutor was trained prior to working with the student to determine if a peer tutor who had no prior history with the student could work effectively with minimal disruptions from the onset. Data were also measured on the student's aberrant behaviors and his compliance before, during, and after training the peer tutors. Results indicated that the peer tutors learned to provide appropriate commands and specific praise and to reduce negative statements. More important, as a collateral effect of the training program, the student's aberrant behaviors decreased and his compliance to requests improved.

Behavior Therapy↗
PubMed1994

Restenosis following subclavian artery angioplasty for treatment of coronary-subclavian steal syndrome: definitive treatment with Palmaz-stent placement.

We report a case of progressive angina pectoris 4 years post coronary bypass surgery, in which the left internal mammary artery (LIMA) was grafted to the native left anterior descending coronary artery. The coronary-subclavian steal phenomenon was proven angiographically with retrograde reflux through the LIMA graft into the distal subclavian vessel, downstream from a critical stenosis at the origin of the subclavian artery. After initially successful angioplasty of the ostial subclavian lesion, restenosis and return of angina prompted repeat dilatation and placement of a Palmaz 154-M stent. Follow-up catheterization has demonstrated persistent patency at the stented site and absence of coronary steal.

Angina Pectoris↗
PubMed1994

An evaluative study of a community health service development.

This paper describes a research study designed to evaluate a community health service development in one health authority in rural England. The study compared two types of primary care teams working towards the same objectives. Surveys of patients and staff in the health authority were conducted about a range of issues, defined by the original aims of the scheme. Measures were made of care received by people over 75 years of age, consumer satisfaction, staff experiences of the multi-disciplinary team, job satisfaction and liaison with social services personnel. Few differences existed between the two forms of care on all of these measures. This paper contains a discussion of the findings alongside an examination of the implications for future health service developments, particularly flagship enterprises such as nursing development units. The importance of well established baseline measurements is emphasized by both the research findings and the discussion.

Aged↗
PubMed1994

Treatment regimen and side effects of treatment measures.

The severity of asthma can be judged by many features, including the need for medication and associated side effects. Since asthma has both acute and chronic characteristics, therapeutic regimens should be valuable as an instrument to define disease severity and the consequence of intervention. However, because of the variability of asthma severity within each patient, medication quantitation as an index of asthma severity is not without difficulty and limitation. Furthermore, the philosophy of asthma therapy has undergone changes over the past decade. Previously, anti-inflammatory therapy was reserved for only the most severely ill patients. Now, inflammation is recognized as a critical component of asthma, and all patients with active asthma (other than mild symptoms) are recommended to use anti-inflammatory therapy. Although there is little published experience with treatment regimens as an index of disease severity, those that have been used have found validity and reproducibility with this approach. In this paper, a scoring approach to medication use is recommended. Medication is classified into bronchodilator (beta-agonists, theophylline, and anticholinergic) or anti-inflammatory (corticosteroid and cromolyn sodium). Medication scores are given on either a per-use or a new-dosage basis. Furthermore, the eight medications are stratified according to potency (i.e., inhaled corticosteroid < oral corticosteroid < parenteral corticosteroid). From this approach, the severity of an individual patient's asthma can be quantitated, and this value can serve as one instrument to assess disease severity.

Algorithms↗
PubMed1992

Transforming growth factor beta within fibrotic scleroderma lungs.

PURPOSE, PATIENTS, AND METHODS: Since transforming growth factor beta (TGF beta) has been implicated as an important mediator of pulmonary fibrosis, we measured TGF beta protein and gene expression in alveolar epithelial lining fluid (ELF) of fibrotic scleroderma lungs sampled by bronchoalveolar lavage (BAL). TGF beta protein was qualitatively examined by Western blot analysis, and quantitatively by radioreceptor assays. Gene expression was evaluated in BAL mononuclear cells by Northern blot analysis with quantification of relative gene expression by densitometric analysis of the autoradiograms. RESULTS: Normal and scleroderma subjects had a 24-kd protein that comigrated with defined human TGF beta 1 and immunoreacted with anti-TGF beta antibody. The normal population had a significantly higher average TGF beta concentration (705 pM) compared with the scleroderma subjects (177 pM). The TGF beta 1 gene was expressed in amounts that did not significantly differ between the scleroderma and normal groups. On an individual subject basis, the TGF beta concentration variability did not correlate with variations in BAL cellularity or TGF beta 1 gene expression within the recovered mononuclear cells. CONCLUSIONS: It is concluded that both normal and fibrotic lungs have TGF beta 1 present at the alveolar epithelial surface. However, in the fibrotic scleroderma lungs, TGF beta protein content and gene expression were not increased at the alveolar epithelial surface. The simultaneous analysis of TGF beta protein content, gene expression, and cellular constituents within individual ELF specimens showed that the cellular components of the ELF do not appear to be major determinants of TGF beta protein concentration at the alveolar epithelial surface.

Adult↗
PubMed1992

Generalized effects of a peer-delivered first aid program for students with moderate intellectual disabilities.

Peers with mild intellectual disabilities taught first aid skills to 4 students with moderate intellectual disabilities. A multiple probe design across participants was used to examine the effects of the peer teaching program during an acquisition and a partial sequential withdrawal phase. Generalization assessments were conducted in the participants' homes using novel, randomized simulated injuries. Results suggested that the peer teaching program resulted in acquisition of first aid skills, and the participants' skills generalized to the home, to novel simulated-injury locations, and to new trainers. Additionally, a more detailed analysis of the generalized responding suggested that when given a choice among first aid materials, participants treated burns using large adhesive bandages rather than the materials used in training. Participants also successfully treated injuries when novel instructional cues were used. The findings are discussed with respect to training issues, generalization and maintenance of the acquired skills, and the use of peer tutors with disabilities.

Child↗
PubMed1991

Complement subcomponent C1q stimulates Ig production by human B lymphocytes.

The regulation of Ig production by human B lymphocytes is a complex process involving interactions among B cells, APC, T lymphocytes and soluble factors including activation, growth, and differentiation factors. Components of the complement system, including C3a, C3b, C3d, and C5a, have been shown to influence various stages in this process. In this study, we demonstrate that the C1q subcomponent of complement binds to both small resting and large activated B cells and stimulates immunoglobulin production by Staphylococcus aureus Cowan-activated tonsillar B lymphocytes. This effect is present whether C1q is added to the B cells either at the beginning or near the end of a 7-day culture period and is not associated with enhancement of proliferation. The C1q stimulation of Ig production is, however, associated with increased steady state levels of mRNA for the mu Ig H chain. Furthermore, C1q stimulated IgM production by the human B cell line SKW 6.4, which is capable of secreting IgM in response to B cell differentiation factors (BCDF). SLE is a disorder frequently associated with polyclonal activation of B lymphocytes. We studied the effect of C1q on B cells from two patients with this disorder and one with an SLE-like illness, all selected for the predominance of either IgM or IgG in serum. Spontaneous or BCDF-stimulated Ig secretion was of the isotype predominant in vivo, whereas C1q selectively stimulated B cells to produce the other isotype (IgG vs IgM). Thus, C1q interacts with B lymphocytes in a manner distinct from that of BCDF found in mixed lymphocyte supernatants. C1q may be an important factor influencing the production of Ig by B lymphocytes in normal individuals and in patients with abnormalities of B cell activity.

B-Lymphocytes↗
PubMed1991

Intracellular signaling events associated with the induction of proliferation of normal human B lymphocytes by two different antigenically related human B cell growth factors (high molecular weight B cell growth factor (HMW-BCGF) and the complement factor Bb).

High molecular weight B cell growth factor (HMW-BCGF) and the complement component, Factor B, are antigenically related. HMW-BCGF and the physiologic Factor B activation fragment Bb, are both mitogenic for B lymphocytes and compete for binding to the B cell plasma membrane (Peters, M., Ambrus, J. L., Jr., Fauci, A., and Brown, E. (1988) J. Exp. Med. 168, 1225-1235). To understand which second messengers that occur after ligand-receptor interaction are associated with mitogenesis, we have examined the early signaling events after stimulation of activated B cells with these related growth factors. HMW-BCGF but not Bb increased [cAMP]i with a maximum between 45 and 60 min after stimulation. The increase in [cAMP]i was inhibited by indomethacin, suggesting that prostaglandin synthesis is involved in this response. Increase in [cAMP]i induced by HMW-BCGF, cholera toxin, or dibutyryl cAMP was associated with increased expression of the HMW-BCGF receptor, but there was no increase in proliferation of activated B cells when they were stimulated with cAMP agonists other than HMW-BCGF. These data suggest that cAMP is associated with regulation of receptor expression but is neither necessary nor sufficient for induction of proliferation. Both HMW-BCGF and Bb increased cellular levels of diacylglycerol and a water-soluble molecule which could be labeled with both [3H]myoinositol and [14C] glucosamine. However, only HMW-BCGF induced increases in intracellular calcium. Thus, two antigenically related B cell growth factors, HMW-BCGF and Bb, produce overlapping but distinct sets of second messengers after incubation with Sac-activated B cells. Since both induced increases in diacylglycerol and water-soluble inositol, one or both of these molecules may be involved in the proliferative signal generated by the related growth factors. In contrast, the increase in [cAMP]i caused by HMW-BCGF but not Bb is involved in the signal to increase HMW-BCGF receptor expression, but is unrelated to proliferation.

B-Lymphocytes↗