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Biomedical subjects

K Woolley

Publications and source records attributed to K Woolley.

13 recordsLinked to original sources
PubMed2003

Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants.

BACKGROUND AND PURPOSE: Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings. METHODS: We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age. RESULTS: Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes. CONCLUSION: These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.

Anisotropy↗
PubMed2001

Physician-prompting statin therapy intervention improves outcomes in patients with coronary heart disease.

STUDY OBJECTIVE: To evaluate the effectiveness of a posthospital discharge intervention that prompted physicians to increase the use and effectiveness of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in patients with coronary heart disease (CHD). METHODS: Participants were 612 patients with CHD who were admitted to a coronary care unit. The control group (303 patients admitted from October 1-December 31, 1998) received no follow-up intervention. The intervention group (309 patients admitted fromJanuary 1-March 31, 1999) had follow-up letters sent or phone calls made to their primary care physicians with patient-specific recommendations concerning assessment of lipid profiles and statin therapy. Over a 2-year follow-up period, assessment of lipid profiles, use of therapy, and adverse clinical outcomes were compared between the control and intervention groups. RESULTS: At hospital discharge, there was no significant difference in the use of statins between the groups. At each reported follow-up interval, the percentages of patients having lipid profiles measured, being treated with a statin, receiving titrated dosages of a statin, and achieving low-density lipid (LDL) cholesterol goals set by the National Cholesterol Education Program (NCEP) were significantly greater in the intervention group compared with the control group (all p<0.05). At the end of the 2-year follow-up period, nearly three-fourths (72%) of the intervention group were receiving a statin, compared with 43% of the control group. In addition, 55% of the intervention group achieved their NCEP LDL goal, compared with only 10% of the control group. Recurrent myocardial infarction, hospitalization for myocardial ischemia, coronary revascularization, and cardiovascular mortality were significantly reduced in the intervention group compared with the control group (all p<0.05). CONCLUSION: A relatively simple physician-prompting intervention significantly increased assessment of lipid status, frequency of statin use, achievement of LDL treatment goals, and titration of lipid drug dosages. In addition, the improved use of statins significantly reduced adverse cardiovascular outcomes. This intervention tool should be more broadly applied in patient populations eligible to receive these agents.

Aged↗
PubMed2000

Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues.

The capacities to repair minor membrane holes in damaged single cells, and the more major damage sustained when a multicellular tissue is wounded, both involve a series of ancient and highly conserved processes. In this review, we discuss what is known about how the plasma membrane of a single cell and its underlying cortical cytoplasm are repaired following cell damage, and how multicellular wounds to the embryonic and adult skin are also able to heal. Pivotal for all these processes is the actin cytoskeleton and we draw analogies between the actin machineries that drive repair and those that appear to underlie several genetically tractable morphogenetic processes that occur during Drosophila and Caenorhabditis elegans embryogenesis.

Actins↗
PubMed2000

Axis-inducing activities and cell fates of the zebrafish organizer.

We have investigated axis-inducing activities and cellular fates of the zebrafish organizer using a new method of transplantation that allows the transfer of both deep and superficial organizer tissues. Previous studies have demonstrated that the zebrafish embryonic shield possesses classically defined dorsal organizer activity. When we remove the morphologically defined embryonic shield, embryos recover and are completely normal by 24 hours post-fertilization. We find that removal of the morphological shield does not remove all goosecoid- and floating head-expressing cells, suggesting that the morphological shield does not comprise the entire organizer region. Complete removal of the embryonic shield and adjacent marginal tissue, however, leads to a loss of both prechordal plate and notochord. In addition, these embryos are cyclopean, show a significant loss of floor plate and primary motorneurons and display disrupted somite patterning. Motivated by apparent discrepancies in the literature we sought to test the axis-inducing activity of the embryonic shield. A previous study suggested that the shield is capable of only partial axis induction, specifically being unable to induce the most anterior neural tissues. Contrary to this study, we find shields can induce complete secondary axes when transplanted into host ventral germ-ring. In induced secondary axes donor tissue contributes to notochord, prechordal plate and floor plate. When explanted shields are divided into deep and superficial fragments and separately transplanted we find that deep tissue is able to induce the formation of ectopic axes with heads but lacking posterior tissues. We conclude that the deep tissue included in our transplants is important for proper head formation.

Animals↗
PubMed1998

Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells.

BACKGROUND: Chronic cough is a multifactorial condition, which, like asthma, can be associated with eosinophilic airway inflammation. In asthma, airway eosinophilia is believed to be mediated by cytokines such as interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF). The role of these cytokines in chronic cough is unclear. OBJECTIVE: The aim of this study was to examine gene expression for IL-5 and GM-CSF in chronic cough and compare the results with those found in asthma. METHODS: We studied adults with asthma (n = 12), chronic cough responsive to inhaled corticosteroid (ICS-responsive cough) (n = 9), and chronic cough not responsive to inhaled corticosteroid (non-ICS-responsive cough) (n = 4). Bronchoalveolar lavage (BAL) was performed, and cytokine gene expression was assessed by using a semiquantitative reverse transcriptase polymerase chain reaction. RESULTS: IL-5 mRNA was expressed by BAL cells from nine of 12 asthmatic subjects and six of nine subjects with ICS-responsive chronic cough. IL-5 mRNA was not detected in subjects with non-ICS-responsive chronic cough (zero of four subjects, p < 0.05). GM-CSF mRNA was expressed in BAL cells from seven of 12 asthmatic subjects and six of nine subjects with ICS-responsive cough. GM-CSF mRNA was not detected in non-ICS responsive cough subjects (zero of four subjects, p < 0.05). GM-CSF gene expression was related to the degree of methacholine airway responsiveness in asthmatic subjects (r = -0.59). CONCLUSION: We conclude that chronic cough, like asthma, is associated with airway inflammation and gene expression for IL-5 and GM-CSF. Ongoing expression of these cytokines is likely to be related to the persistence of airway inflammation and chronic cough.

Administration, Inhalation↗
PubMed1996

Transforming growth factor beta 1 (TGF beta 1) gene expression by eosinophils in asthmatic airway inflammation.

The increase in thickness of bronchial walls by such structural changes as subepithelial fibrosis contributes to the severity and chronicity of asthma by amplifying airway narrowing. However, the pathogenesis of this structural alteration is not known. Transforming growth factor beta 1 (TGF beta 1) is known to have biologic activities relevant to the cellular and molecular events in subepithelial fibrosis, such as the deposition of collagen I and III and the increase of myofibroblasts beneath the epithelial basement membrane. Therefore, we examined TGF beta 1 gene expression in bronchial biopsy tissues from five severe asthmatics, five mild asthmatics, and five normal subjects using in situ hybridization combined with histochemical staining. Cells expressing TGF beta 1 mRNA were detected in tissues from four normal subjects, one mild asthmatic, and five severe asthmatics. The density of positive cells in severe asthmatic tissues (52.1 +/- 22.7, mean +/- SD/mm2) was significantly greater than that in mild asthmatic tissues (1.0 +/- 1.9/mm2, P < 0.01) or normal tissues (10.5 +/- 10.6/mm2, P < 0.02). The density in mild asthmatic tissues was not significantly different from that in normal tissues. The vast majority of positive cells in severe (99.1 +/- 1.7%) and mild (100%) asthmatic tissues were identified as eosinophils. In contrast, eosinophils constituted a small portion of positive cells (20.8 +/- 21.6%) in normal tissues. These results indicated that TGF beta 1 mRNA was overexpressed in severe asthmatics and that the main source of the mRNA was eosinophils, suggesting that eosinophils play an important role in the pathogenesis not only of inflammation but also of structural changes, such as subepithelial fibrosis, in asthmatic airways.

Adult↗
PubMed1995

Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils.

Nasal polyposis and asthma are inflammatory conditions of the airways characterized by infiltration of activated inflammatory cells, particularly eosinophils. IL-4 is a multifunctional cytokine considered to play an important role in eosinophilic inflammation. We examined the cellular distribution of immunoreactive IL-4 in nasal polyps, as well as in the bronchial mucosa of both nonasthmatic control subjects (n = 6) and patients with well-characterized mild asthma (n = 6) subjected to a diluent or an allergen challenge. To determine eosinophilic contribution, tissue sections were counterstained with FITC after IL-4 immunostaining. No eosinophils were observed in the bronchial mucosa of nonasthmatic subjects. Nasal polyp tissues contained approximately 15 times more eosinophils per mm2 compared with bronchial tissues from asthmatics after a diluent challenge. Allergen challenge resulted in a marked increase in eosinophil density in bronchial tissues. A negligible number of cells immunostaining IL-4 was observed in bronchial tissues from nonasthmatic control subjects. The density of IL-4-positive cells in nasal polyp tissues was almost three times greater compared with asthmatics bronchial tissues after a diluent challenge. Approximately 90% of the IL-4-positive cells in bronchial tissues did not exhibit fluorescence after FITC counterstaining; in contrast, about 80% of the IL-4-positive cells in nasal polyp tissues did. We also show that peripheral blood eosinophils from allergic subjects express IL-4 mRNA by Northern blot analysis, particularly on stimulation with secretory IgA immune complexes. Finally, the supernatant of stimulated eosinophils contained approximately 50 pg/10(6) cells of IL-4 as determined by ELISA. These data demonstrate that eosinophils express the message and release IL-4 in vitro, and that these cells are the primary source of immunoreactive IL-4 in tissues undergoing chronic severe mucosal inflammation.

Adult↗
PubMed1995

Phase II trial of a 75-mg/m2 dose of docetaxel with prednisone premedication for patients with advanced non-small cell lung cancer.

BACKGROUND: A prior Phase II study of a 100-mg/m2 dose of docetaxel conducted at the Memorial Sloan-Kettering Cancer Center (New York, NY) demonstrated a 38% response rate with grade 3 or 4 neutropenia in 76% of the patients and a grade 2 or greater rash or infusion-related reaction in 41% and 34% of the patients, respectively. The current Phase II study sought to determine the activity of a 75-mg/m2 dose of docetaxel to establish whether this lower dose, combined with prednisone, ameliorates toxicity. METHODS: Twenty untreated patients with advanced non-small cell lung cancer (NSCLC) received a 1-hour 75-mg/m2 dose of docetaxel every 21 days. Fifty milligrams of prednisone were administered twice the day before chemotherapy and once each of the next 3 days. Patients' disease-related symptoms were assessed prospectively using the Lung Cancer Symptom Scale (LCSS). RESULTS: All patients were assessable for response and toxicity. Five patients had a major objective response (25%; 95% confidence interval, 11-50%). The median duration of response was 9.1 months. The projected 1-year survival was 71%. Grade 3 or 4 neutropenia occurred in 70% of the patients. Grade 2 or greater rash and infusion-related reactions decreased to 25% each. Analysis of the LCSS measurements found that six of nine component symptoms improved on Day 22, and all improved when baseline measurements were compared with the best value for each patient during the study. CONCLUSIONS: Docetaxel administered at a dose of 75 mg/m2 every 21 days shows significant antitumor activity in untreated patients with NSCLC: Neutropenia is comparable with that observed at a 100-mg/m2 dose. The number of infusional reactions and rash decreased when docetaxel at this dose was administered with prednisone. Based on response rates observed in trials using a 100-mg/m2 dose with similar degrees of neutropenia, a 100-mg/m2 dose with steroid pretreatment is recommended future trials.

Adult↗
PubMed1995

Eosinophils as a potential source of platelet-derived growth factor B-chain (PDGF-B) in nasal polyposis and bronchial asthma.

Tissue remodeling in bronchial tissues from asthmatics as well as in nasal polyp (NP) tissues includes sub-basement membrane deposition of collagen, stromal deposition of extracellular matrix protein, and hypertrophy/hyperplasia of airway smooth muscle cells, which are relevant to the cellular and molecular events induced by platelet-derived growth factor (PDGF). Therefore, we investigated the localization of mRNA and protein of PDGF-B chain (PDGF-B) in NP tissues and bronchial tissues from mild and severe asthmatics by in situ hybridization and immunohistochemistry, respectively. Cells expressing PDGF-B mRNA were found in all nine NP tissues and in bronchial tissues from 2 of 6 normal subjects, 2 of 5 mild asthmatics, and all of 6 severe asthmatics examined. The vast majority of cells expressing PDGF-B mRNA were eosinophils in NP (99.7 +/- 0.2%, mean +/- SD) and asthmatic bronchial tissues (75.0 and 77.8% in mild asthma, and 92.7 +/- 8.1% in severe asthma), but no cells expressing PDGF-B mRNA were eosinophils in normal bronchial tissues. The number of cells expressing the gene in severe asthma tissues (122.3 +/- 32.2/mm2) was similar to that in NP tissues (152.8 +/- 73.9/mm2) and greater than that in mild asthma tissues (4.7 +/- 7.6/mm2, P < 0.01), which was not significantly greater than that in normal bronchial tissues (3.4 +/- 5.2/mm2). Furthermore, we detected immunolocalization of PDGF-B in NP tissues and in asthmatic bronchial tissues. The eosinophils purified from peripheral blood were demonstrated to express PDGF-B gene transcript and immunoreactivity after stimulation with A23187.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1975

Beneficial effects of penicillamine treatment on hereditary avian muscular dystrophy.

Hereditary muscular dystrophy in chickens of the New Hampshire strain was treated with penicillamine from the 9th day after hatching to the 425th day. The adult maintenance dose for males was 50 mg/kg per day and for females, 13-65 mg/kg per day. In avian dystrophy, deterioration of the muscle fibers is evidenced in the 2nd mo by an inability of the birds to rise after falling on their backs and by a progressive rigidity of the wings. The drug delayed the onset of symptoms and partially alleviated the debilitating aspects of the disease. Penicillamine produced three major improvements: (a) better righting ability when birds were placed on their backs; (b) greater wing flexibility; (c) and suppression of plasma creatine phosphokinase activity. The results are statistically analyzed and discussed in relationship to Duchenne dystrophy. Normal birds were not affected by penicillamine as judged by these parameters. The rationale for using penicillamine, a sulfhydryl compound with reducing properties, was (a) to attempt to protect essential thiol enzymes in the anabolic and glycolytic pathways against inactivation and (b) to prevent collagen cross-linking and deposition in muscle. Although the precise mechanism of drug action has not been determined. the possible role of penicillamine in mitigating the symptoms of genetic dystrophy in man is under consideration. Further, penicillamine may have a more generalized application i the prevention of contractures in a variety of neuromuscular disorders.

Animals↗
PubMedDate not supplied

Pulmonary parenchymal manifestations of mitral valve disease.

Pulmonary parenchymal manifestations of mitral valve disease are the result of either pulmonary venous hypertension in mitral stenosis or abnormal regurgitant flow into pulmonary veins in mitral insufficiency. Typical radiographic findings in mitral stenosis include pulmonary vascular cephalization; interstitial, perivascular, and occasionally alveolar pulmonary edema; diffuse alveolar hemorrhage; hemosiderosis; and pulmonary ossification. Signs of interstitial pulmonary edema are frequently visible and include septal lines. Radiographic findings in diffuse alveolar hemorrhage consist of diffuse, confluent acinar or ground-glass areas of increased opacity, often sparing the peripheral parenchyma and creating the so-called window frame effect. Hemosiderosis is characterized by small, ill-defined nodules or by coarse reticular areas of increased opacity with a bias for the middle and lower lung regions. Ossification manifests as densely calcified, 1-5-mm nodules, mainly in the middle and lower lungs, with a tendency for confluence and the occasional presence of trabeculae. Imaging findings in mitral regurgitation depend on the acuteness of the disease. The most common parenchymal manifestations of acute mitral regurgitation are symmetric alveolar and interstitial pulmonary edema with indistinct, engorged pulmonary vessels and cephalized blood flow. Familiarity with these manifestations can expedite diagnosis, particularly in rare cases of unsuspected mitral valve disease.

Humans↗
PubMedDate not supplied

Value for money in the NHS.

Value for money is becoming increasing important in the current NHS climate. The Audit Commission, a statutory body appointed to provide an external audit service for the NHS in England and Wales, aims to work with audited bodies to identify economy, efficiency and effectiveness in the services offered by the NHS to help improve patient care.

Cost-Benefit Analysis↗