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Biomedical subjects

E O'Keefe

Publications and source records attributed to E O'Keefe.

At least 19 recordsLinked to original sources
PubMed2002

Clinical equivalence trial on budesonide delivered either by the Novolizer multidose dry powder inhaler or the Turbuhaler in asthmatic patients.

BACKGROUND AND OBJECTIVES: To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer, i.e. a multidose dry powder inhaler, or by the Pulmicort Turbuhaler in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment. METHODS: A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV(1)), need for anti-inflammatory therapy, inhalation of beta(2)-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 microg salbutamol. Primary variable was FEV(1), secondary were other pulmonary function test variables, PC(20)FEV(1) for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables. RESULTS: The comparison of the FEV(1) at study endpoint indicated that the Novolizer was at least as efficacious as the Turbuhaler (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups. CONCLUSIONS: The budesonide Novolizer is therapeutically equivalent to the Pulmicort Turbuhaler for the long-term treatment of patients with mild to moderate persistent asthma.

Adolescent↗
PubMed2000

Scintigraphic comparison of budesonide deposition from two dry powder inhalers.

Chlorofluorocarbons (CFCs), used in metered dose inhalers (MDIs), have been identified as being deleterious to the environment leading to a ban on their production. Dry powder inhalers (DPIs) are a widely used alternative to MDIs. One disadvantage of DPIs is that in vivo lung deposition can be influenced by the patient's inspiratory flow rate. The ASTA Medica multi-dose dry powder inhaler (AM-MDPI) has been designed to offer low resistance on inhalation, so that asthmatic patients can achieve inhaled flow rates of approximately 90 L x min(-1). The aim of the study was to evaluate the in vivo deposition of budesonide from the AM-MDPI at different flow rates and to compare this with delivery from a Turbuhaler DPI at a high flow rate. The study was a scintigraphic, randomized, crossover study in which 13 healthy volunteers inhaled a single 200 microg dose of radiolabelled budesonide on four separate occasions with a minimum 44-h washout period between dosings. At the lowest flow rate of 54 L x min(-1), comparable to that for the Turbuhaler (58 L x min(-1)), a similar percentage of the metered dose was delivered to the lung (AM-MDPI median 19.9%; Turbuhaler median 21.4%). At high flow rate (peak inspiratory flow rate 99 L x min(-1)) the AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered dose) than at 65 L x min(-1) or 54 L x min(-1) (median 25.0% and 19.9% of metered dose, respectively), thus demonstrating flow rate dependence. The pattern of regional lung deposition from the AM-MDPI was similar for all three inhalation manoeuvres. It was concluded that the ASTA Medica multi-dose dry powder inhaler achieves at least as much deposition of budesonide in the lungs as a Turbuhaler when used at similar inspiratory flow rates.

Administration, Inhalation↗
PubMed1998

Differential effects of new-generation H1-receptor antagonists in pruritic dermatoses.

In search of an improved treatment of pruritic dermatoses, we have studied azelastine, a novel H1-receptor antagonist, during a 2-week treatment period, using a double-blind, placebo-controlled design. The potent H1-antagonist cetirizine was used for comparison. Symptoms were recorded daily by the patients on a diary card, using a 4-point scale. The same parameters and adverse events were evaluated at weekly intervals, and global improvement was evaluated at the end of treatment. In all 230 evaluable patients with moderate to severe itching, azelastine caused an overall significant improvement in comparison to placebo (P = 0.02), with significance also for pruritus (P = 0.01 after 1 week and P = 0.02 after 2 weeks). Both drugs reduced itching more effectively in urticaria than in atopic eczema. Azelastine was superior to cetirizine in reducing pruritus, whereas cetirizine caused a more marked reduction of whealing. Both drugs rarely caused fatigue and dry mouth, but taste perversion occurred only in azelastine-treated patients (9.7%) and headaches only with cetirizine (10.4%). Therefore, the two H1-blockers exert differential effects on pruritus verses whealing and a distinctive adverse events pattern. The data also underline the low efficacy of antihistamines in atopic eczema, compared to urticaria.

Adolescent↗
PubMed1997

Independent epidemics of heterosexual and homosexual HIV infection in South Africa--survival differences.

Survival with HIV infection is shorter in sub-Saharan Africa than in developed countries. The pattern of HIV transmission in our region has changed from homosexual to heterosexual, with viral subtypes similar to those in North America/Europe and Central Africa, respectively. We compared survival for the two transmission patterns after AIDS, and after the first CD4+ lymphocyte counts < 200/microliter and < 50/microliter, for adults presenting 1988-1993. Antiretroviral therapy was excluded. There were 180 homosexuals (63% White, 56% employed) and 314 heterosexuals (67% Black, 34% employed). Extrapulmonary tuberculosis was the AIDS-defining diagnosis in 36/90 heterosexuals and 5/58 homosexuals (p < 0.0001). Survival after AIDS was longer in heterosexuals (p = 0.0015), but AIDS occurred earlier as shown by their higher CD4+ count at AIDS onset (median 98/microliter vs. 40/microliter; p = 0.036). Survival was similar in the two groups after first CD4+ count < 200/microliter and < 50/microliter. Race, socioeconomic status and morbidity are markedly different in the two transmission groups. AIDS occurs with less severe immune suppression in heterosexuals, with correspondingly longer survival. Survival after defined CD4+ counts, however, is remarkably similar.

AIDS-Related Opportunistic Infections↗
PubMed1997

Intergroup comparisons of oral lesions in HIV-positive South Africans.

OBJECTIVE: To determine whether there are any differences in the oral manifestations of sub-groups of persons with HIV. These data could provide information for planning of oral health promotion and prevention programmes. DESIGN: A comparative inter-group cross-sectional investigation of the oral manifestations of HIV. Ethnic, gender and sexual orientation differences were taken into consideration. SETTING: Three large general hospitals that offer comprehensive medical investigations and care to persons with HIV. SUBJECTS AND METHODS: A total of 485 HIV-positive adults participated. Clinical examination and, where necessary, swabs or smears of lesions for microbiology, biopsies for histology. MAIN OUTCOME MEASURES: Presence of lesions, associated signs, incidence and type of micro-organisms. RESULTS: A total of 485 HIV-positive persons were examined over a period of 3 years consisting of 225 Blacks, 191 Coloureds (persons of 'mixed' descent) and 69 Whites. Data were analysed using, where relevant, the chi 2 test or Fisher's exact test. Heterosexual males revealed a higher prevalence of all oral lesions combined when compared with heterosexual females. A similar finding was evident when HIV-associated periodontal diseases was compared in these two groups. Homosexual males had a higher prevalence of candidal infections than heterosexual males. Coloured heterosexuals had a higher prevalence of oral lesions combined than black heterosexuals. All these results showed statistical significance. CONCLUSIONS: The study tends to show that different patterns of prevalence emerge when inter-group comparisons are made of oral soft tissue diseases evident in HIV-infected South Africans.

Adolescent↗
PubMed1993

Localization of adducin in epidermis.

On the cytoplasmic side of the plasma membrane of erythrocytes there is a dense protein filament matrix that maintains the shape of the cells. The main constituents of this system, actin and spectrin, which have also been detected in keratinocytes and fibroblasts, are known to be linked in erythrocytes in a network structure by additional proteins such as band 4.1 and adducin. The interaction between actin and spectrin, mediated by adducin, is regulated by calmodulin and protein kinase C. Because we have previously found adducin in cultured keratinocytes, we investigated epidermis by immunochemical techniques. We found adducin to be localized at cell-cell contact sites in epidermis using affinity-purified antibodies against human erythrocyte adducin. Immunofluorescence of epidermis revealed an intense fluorescence in the basal layer, whereas stratum spinosum and stratum granulosum showed moderate staining. There was intense staining at sites of cell-cell contact in cultured human keratinocytes. Immunoblot analysis indicated the presence of adducin polypeptides of 103 kd and 97 kd in epidermis, but in cultured keratinocytes only the higher molecular weight form could be detected. This study indicates adducin, a regulatory protein in erythrocytes, is also present in epidermis. Its localization suggests that it may be involved in the formation of the microfilament matrix of the membrane skeleton at cell-cell contact sites.

Actins↗
PubMed1991

Minoxidil: inhibition of proliferation of keratinocytes in vitro.

Previous studies have suggested that minoxidil stimulates growth of keratinocytes, possibly in a manner similar to the action of epidermal growth factor. Using both a short-term assay, thymidine incorporation, and a longer term assay, cell counting, to assess proliferative growth, we tested the activity of minoxidil in human keratinocyte cultures grown in 0.1 mM Ca(++). Minoxidil failed to stimulate growth in these assays. At concentrations of 5-10 micrograms per ml, minoxidil showed half-maximal inhibition of both EGF- and placental extract-stimulated thymidine incorporation. Minoxidil also inhibited proliferative growth in the presence or absence of placental extract. Direct measurement of the ability of minoxidil to compete for binding to the EGF receptor indicated that minoxidil probably does not bind to the EGF receptor. Minoxidil was not toxic, as keratinocytes continued to survive and grow, although at a slower rate, in the presence of minoxidil.

Cell Division↗
PubMed1991

Irritable bowel syndrome in the elderly.

Although few studies to elucidate the epidemiology and pathophysiology of the irritable bowel syndrome (IBS) in people over the age of 65, it is our thesis that the problem is underrecognized in older people. The available data suggest that 10% to 20% of elderly people in the general population have IBS. The causes remain unknown, but age-related changes are unlikely to alter the underlying pathogenesis. Treatment is still largely empiric, symptomatic, and often unsatisfactory; the problems of treating IBS in the elderly are compounded by the frequency of untoward side effects of drugs in this age group.

Aged↗
PubMed1990

Oral clindamycin and ciprofloxacin therapy for diabetic foot infections.

Infected foot ulcers are a common complication in persons with diabetes. In general, treatment consists of intravenous administration of antibiotics, for which the patients are customarily hospitalized. The average length of hospital stay for this therapy in our institution is 15.6 days. We evaluated a regimen of oral clindamycin plus ciprofloxacin, which patients could take at home, with respect to the clinical eradication of the infection and treatment cost savings. Our results demonstrated that with these oral agents, patients' length of hospital stay was greatly reduced, and the pharmacy realized significant cost avoidance.

Administration, Oral↗
PubMed1989

Adducin: Ca++-dependent association with sites of cell-cell contact.

Adducin is a protein recently purified from erythrocytes and brain that has properties in in vitro assays suggesting a role in assembly of a spectrin-actin lattice. This report describes the localization of adducin to plasma membranes of a variety of tissues and the discovery that adducin is concentrated at sites of cell-cell contact in the epithelial tissues where it is expressed. Adducin in tissues and cultured cells always was observed in association with spectrin and actin, although spectrin and actin were evident in the absence of adducin. In sections of intestinal epithelial cells spectrin was present on all plasma membrane surfaces while adducin was restricted to the lateral cell borders. Adducin also was not detected in association with actin stress fibers in cultured cells. The presence of adducin at cell-cell contact sites of cultured epithelial cells requires extracellular Ca++ and occurs within 15 min of addition of 0.3 mM Ca++. Redistribution of adducin after addition of extracellular Ca++ is independent of formation of desmosomal and adherens junctions since assembly of adducin at contact sites requires lower concentrations of Ca++ and occurs more rapidly than redistribution of desmoplakin or vinculin. Treatment of keratinocytes and MDCK cells with nanomolar concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA) induces redistribution of adducin away from contact sites. The effect of TPA may be a direct consequence of phosphorylation of adducin, since adducin is phosphorylated in TPA-treated cells and the phosphorylation of adducin occurs before disassembly of adducin from sites of cell-cell contact. Spectrin and adducin are both present in a detergent-insoluble form at cell-cell contact sites of cultured cells. These observations are consistent with the idea that adducin recognizes and associates with specific "receptors" localized at regions of cell-cell contact and promotes assembly of spectrin into a more stable structure, perhaps analogous to the highly organized spectrin-actin network of erythrocyte membranes.

Actins↗
PubMed1987

Infusion phlebitis associated with a programmable syringe-pump system versus gravity-feed minibottles.

The occurrence of infusion phlebitis in patients receiving intravenous antibiotics via a gravity-feed minibottle system versus a new syringe-pump system was compared. Patients at least 18 years old who had indwelling intermittent injection sites inserted for medication administration were randomized to either the minibottle system or the syringe-pump system. Antibiotics in minibottles were diluted in 50-100 mL of 5% dextrose injection; in the syringe-pump group, aminoglycoside antibiotics were diluted in 0.9% sodium chloride injection and all other antibiotics were diluted in sterile water for injection. Antibiotics were not piggybacked into running primary infusions in any of the study patients, and no other medications except for 0.9% sodium chloride flushes were administered through the catheters. All catheters were inserted in peripheral veins and evaluated for phlebitis by i.v. nurse specialists using standardized criteria. Catheters were changed upon the occurrence of grade 1 phlebitis or after a period of three days without the development of phlebitis. Over an 18-week period, 85 catheter sites (53 syringe-pump group versus 32 minibottle group) were evaluated in 30 patients (14 syringe-pump group versus 16 minibottle group). The mean +/- S.D. catheter life in both groups was 50.6 +/- 20 hours. Phlebitis occurred in 62% of syringe-group sites versus 66% of minibottle-group sites; the incidence and severity of phlebitis were not significantly different between groups. The majority of catheter sites were infused with cefazolin sodium. The potential for phlebitis using the syringe-pump system in this study appears to be similar to that of the gravity-feed minibottle system when appropriate diluents, diluent volumes, and infusion rates are used.

Adult↗
PubMed1984

Insulin inhibits the glucocorticoid-mediated increase in hepatocyte EGF binding.

Hydrocortisone and dexamethasone produced a time-dependent increase [125I]epidermal growth factor [( 125I]EGF) binding in primary cultures of isolated rat hepatocytes. Maximally effective doses of glucocorticoids resulted in a 70-100% increase in binding. The effect was similar when hepatocytes were maintained on collagen-coated plates or directly on culture dishes. The glucocorticoid-mediated increase in [125I]EGF binding could be detected after 4 h exposure to glucocorticoid and was substantial by 8 h. The major effect of glucocorticoid appeared to be to increase the number of EGF receptors. While insulin (100 nM) had no effect on basal [125I]EGF binding, it significantly inhibited the increase produced by the glucocorticoid. Since the inhibitory effect of insulin was only observed when insulin was added with the inducing glucocorticoid, insulin appears to inhibit an early hydrocortisone-mediated event.

Animals↗
PubMed1982

Elevated intracellular concentrations of cyclic AMP inhibited serum-stimulated, density-arrested BALB/c-3T3 cells in mid G1.

The stimulation of DNA synthesis in quiescent, density-arrested BALB/c-3T3 cells by platelet-derived growth factor in plasma-supplemented medium was inhibited by the presence of isobutylmethylxanthine (IBMX) and cholera toxin, although neither IBMX or cholera toxin when used alone inhibited the stimulation of DNA synthesis. The cells were reversibly inhibited in mid G1 at a point 6 hr prior to the initiation of DNA synthesis. The inhibition of cell cycle traverse was associated with a 10-15 fold increase in cellular cyclic AMP concentration over basal levels. The reversal of this inhibition by removal of IBMX was correlated with a dramatic decrease in cyclic AMP levels. The traverse of G1 and the initiation of DNA synthesis after release from the cholera toxin and IBMX inhibition was dependent on the presence of plasma in the medium. Either somatomedin C (10-20 ng/ml) or insulin (10(-6)-10(-5) M) completely replaced the plasma requirement for late G1 progression and entry into S phase. Once the inhibited cells were released from the IBMX and cholera toxin block a subsequent increase in cyclic AMP did not prevent entry into S phase. The presence of cholera toxin alone inhibited the stimulation of human dermal fibroblasts. The elevation of intracellular cyclic AMP levels in the human dermal fibroblasts by cholera toxin was two to three fold greater than that found in the BALB/c-3T3 cells in the presence of cholera toxin and the IBMX.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Epidermal growth factor receptor in human epidermal cells: direct demonstration in cultured cells.

The interaction of [125I] labeled murine epidermal growth factor (EGF)( with cultured human keratinocytes has been studied. Epidermal cells from neonatal foreskins were propagated to confluence in 24-well culture trays and incubated with [125I] EGF for binding assays. Association reached equilibrium within 2-4 hr at 4 degrees and slightly earlier at 37 degrees. EGF bound at 37 degrees dissociates very slowly from cells, since it can be shown to enter cells and is degraded to trichloracetic-acid-soluble material. Cells exposed to chloroquine, an inhibitor of lysosomal enzymes, fail to degrade internalized [125I] EGF. Scatchard plots of the binding data yield a dissociation constant of 1 X 10(-9) m and show that epidermal cells bind approximately 3-4 X 10(4) molecules of EGF. Cells exposed to EGF alter their ability to bind EGF by decreasing the number of binding sites in a time- and concentration-dependent manner. Differentiation of epidermal cells in culture poses a problem in assessment of binding of EGF and possibly of other biologically active ligands, since cells lose the ability to bind EGF as they differentiate. These findings indicate that isolated epidermal cells possess a functional receptor for EGF which binds and responds to EGF in a manner similar to that described for other cells.

Animals↗
PubMed1980

Use of immunoglobulin-loaded protein A-bearing staphylococci as a primary solid phase immunoadsorbent in radioimmunoassay.

Protein A-bearing formalinized heat-inactivated Staphylococcus aureus bind rabbit 125I-IgG with high capacity of IgG for antigen. The affinity of immobilized IgG for antigen is equal to the affinity of soluble antibody, and the capacity for antigen approximates the capacity of soluble antibody for antigen. 125I-IgG bound to high affinity sites on bacteria is not substantially displaced in the presence of human serum after 4 h at 4 degrees C, but rabbit immunoglobulin can displace bound rabbit IgG. Protein A-bearing bacteria which have adsorbed IgG free from protease activity in antiserum provide a stable, sensitive, primary solid phase adsorbent with unique features for radioimmunoassay. Sedimentation characteristics of bacteria permit facile separation of bound from free ligand by centrifugation of the primary antibody. Immunoglobulin-loaded staphylococci can adsorb ligand from serum, simultaneously purifying and concentrating ligands for measurement in a single subsequent step. Immunoglobulin-bearing bacteria can be used directly in biological fluids containing immunoglobulin, such as serum and culture media. Improved economy of staphylococci, low nonspecific binding, high functional capacity, stability, and unique characteristics of radioimmunoassay using immunoglobulin-loaded staphylococci compare favorably with conventional solid phase adsorbents.

Animals↗