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Biomedical subjects

C Flynn

Publications and source records attributed to C Flynn.

At least 19 recordsLinked to original sources
PubMed2006

Zincergic innervation of the forebrain distinguishes epilepsy-prone from epilepsy-resistant rat strains.

Zinc is released from a subset of cerebral cortical neurons whereupon it exerts a powerful modulatory influence on excitatory and inhibitory neurotransmission. A number of studies have suggested that alterations in the regulation of zinc may contribute to the genesis of epilepsy. Here, we tested this hypothesis by examining the distribution of zinc-containing axon terminals in rats selectively bred for an innate susceptibility (FAST) or resistance (SLOW) to the development of kindling-induced seizures. Zinc was stained histochemically and levels of staining were quantitatively assessed. We found that the levels of synaptic zinc were significantly lower in the SLOW rats throughout the telencephalon. This relative reduction was most pronounced in limbic cortices where levels were less than 30% of FAST rats. These results suggest that innate differences in the homeostatic regulation of synaptic zinc, particularly in limbic cortices, may underlie differences in epileptogenicity.

Afferent Pathways↗
PubMed2006

Antihistamines and/or decongestants for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated developmental delay. Treatment remains controversial. The effectiveness of antihistamines, decongestants and antihistamine/decongestant combinations in promoting the resolution of effusions has been assessed by randomized controlled trials. OBJECTIVES: The objective of this review is to determine whether antihistamine, decongestant, or combination therapy is effective in treating children who present with OME. SEARCH STRATEGY: The Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2006), EMBASE (1974 to 2006), MEDLINE (1951 to 2006) and a gray literature database were searched using a search strategy created by an experienced medical librarian. The date of the last search was March 2006. Reference lists from included studies and relevant reviews were searched by hand; pharmaceutical manufacturers of antihistamines and decongestants and first authors of included studies were contacted to identify other potentially relevant studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) using antihistamines, decongestants or antihistamine/decongestant combinations as treatment for OME in children were selected. We excluded trials that randomized on the basis of acute otitis media (AOM) even though OME was also studied in follow up. DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by two authors independently using standardized data extraction forms and methods. The methodological quality of the included studies was independently assessed by two authors. Dichotomous results were expressed as a relative risk with 95% confidence intervals using a fixed-effect model when homogeneous and a random-effects model when heterogeneous. Nearly all outcomes analysed were homogeneous. Continuous results were discussed qualitatively. Statistical analysis was conducted using RevMan software. MAIN RESULTS: No statistical or clinical benefit was found for any of the interventions or outcomes studied. However, treated study subjects experienced 11% more side effects than untreated subjects (number needed to treat to harm = 9). AUTHORS' CONCLUSIONS: Because the pooled data demonstrate no benefit and some harm from the use of antihistamines or decongestants alone or in combination in the management of OME, we recommend against their use.

Child↗
PubMed2004

Beta2-agonists for acute bronchitis.

BACKGROUND: The optimal treatment for acute bronchitis is not clear. Because many patients with acute bronchitis have airflow limitation as well as cough, beta2-agonists may be useful. OBJECTIVES: To determine whether beta2-agonists improve the symptoms of acute bronchitis in patients who do not have underlying pulmonary disease. SEARCH STRATEGY: The Cochrane Library (through August 2000), MEDLINE (1966 to 2000), EMBASE (1974 to 2000), and Conference Proceedings using "bronchodilator (exp)", "adrenergic beta-agonist (exp)", or "sympathomimetics (exp)" and "bronchitis" or "cough"; Science Citation Index for referenced publications; and letters to manufacturers of beta2-agonists. An updated search of the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2003); MEDLINE (January 2000 to July 2003); EMBASE (January 2000 to July 2003) was run in July 2003. SELECTION CRITERIA: Trials in which patients (adults or children over two years of age) without known pulmonary disease who were diagnosed with acute bronchitis or acute cough without other cause were randomized to beta2-agonist versus placebo, no treatment, or alternative treatment. DATA COLLECTION AND ANALYSIS: Three reviewers independently first selected outcomes and evaluated trial quality while blinded to study results, and then extracted data. Trials in children and in adults were analyzed separately. MAIN RESULTS: Two trials in children (n = 109) with acute cough and no evidence of airway obstruction did not find any benefits from beta2-agonists. Combined data did not show a significant difference in daily cough scores between patients given oral beta2-agonists and those in the control groups. Five trials in adults (n = 418) with acute cough or acute bronchitis had mixed results, but overall summary statistics did not reveal any significant benefits from oral (three trials) nor inhaled (two trials) beta2-agonists. There were no significant differences in daily cough scores nor in the number of patients still coughing after seven days (control rate 73%; RR = 0.77, 95% CI 0.54-1.09). Subgroups of patients with evidence of airflow limitation had lower symptom scores if given beta2-agonists in one trial; and the trials that did note quicker resolution of cough in patients given beta2-agonists were those that had a higher proportion of patients with wheezing at baseline. Patients given beta2-agonists were more likely to report tremor, shakiness, or nervousness than patients in the control groups (for trials in children control rate 0%; RR 6.76, 95% CI 0.86 to 53.12, NNH 9, 95% CI 5 to 100; for trials in adults, control rate 11%; RR 7.94, 95% CI 1.17 to 53.94, NNH 2.3, 95% CI 2 to 3). REVIEWER'S CONCLUSIONS: There is no evidence to support using beta2-agonists in children with acute cough who do not have evidence of airflow obstruction. There is also little evidence that the routine use of beta2-agonists for adults with acute cough is helpful. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction; but this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.

Acute Disease↗
PubMed2002

Leakage and absorption of isoflurane by different types of anaesthetic circuit and monitoring tubing.

Conductive rubber anaesthetic circuit tubing both absorbs volatile agents and leaks these agents through its walls. We quantified the leakage and absorption properties of the most commonly used plastic materials used to make breathing circuit tubing, relative to conductive rubber. We then compared two different types of plastic tubes used to carry gas to volatile agent monitors; one made of polyvinyl chloride, the other made of polyvinyl chloride lined internally with a thin layer of polyethylene. We found that the three commonly used plastic types used to make anaesthetic circuit tubing all leak less volatile anaesthetic through their walls than conductive rubber. Polyethylene and polypropylene tubing absorb significantly less volatile anaesthetic than conductive rubber; however, this is not the case with polyvinyl chloride tubing. Differences in the leakage and absorption properties of polyvinyl chloride monitoring tubing are not significantly changed by the addition of a thin internal layer of polyethylene. It is therefore not worthwhile incorporating this feature into production.

Absorption↗
PubMed2001

Beta2-agonists for acute bronchitis.

BACKGROUND: The optimal treatment for acute bronchitis is not clear. Because many patients with acute bronchitis have airflow limitation as well as cough, beta2-agonists may be useful. OBJECTIVES: To determine whether beta2-agonists improve the symptoms of acute bronchitis in patients who do not have underlying pulmonary disease. SEARCH STRATEGY: Cochrane Library, MEDLINE, EMBASE, and Conference Proceedings using "bronchodilator (exp)", "adrenergic beta-agonist (exp)", or "sympathomimetics (exp)" and "bronchitis" or "cough"; Science Citation Index for referenced publications; and letters to manufacturers of beta2-agonists. SELECTION CRITERIA: Trials in which patients (adults or children age > 2 years) without known pulmonary disease who were diagnosed with acute bronchitis or acute cough without other cause were randomized to beta2-agonist vs. placebo, no treatment, or alternative treatment. DATA COLLECTION AND ANALYSIS: Three reviewers independently first selected outcomes and evaluated trial quality while blinded to study results, and then extracted data. Trials in children and in adults were analyzed separately. MAIN RESULTS: Two trials in children with acute cough and no evidence of airway obstruction did not find any benefits from beta2-agonists. Five trials in adults with acute cough or acute bronchitis had mixed results, but overall summary statistics did not reveal any significant benefits from beta2-agonists. Subgroups of patients with evidence of airflow limitation had lower symptom scores if given beta2-agonists in one trial; and the trials that did note quicker resolution of cough in patients given beta2-agonists were those that had a higher proportion of patients with wheezing at baseline. Patients given beta2-agonists (whether oral or inhaled) were more likely to report tremor, shakiness, or nervousness than patients in the control groups (NNH for children 9, 95% CI 5 to 100; NNH for adults 2.3, 95% CI 2 to 3). REVIEWER'S CONCLUSIONS: There is no evidence to support using beta2-agonists in children with acute cough who do not have evidence of airflow obstruction. There is also little evidence that the routine use of beta2-agonists for adults with acute cough is helpful. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction; but this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.

Acute Disease↗
PubMed2001

Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway.

To understand how the Wnt coreceptor LRP-5 is involved in transducing the canonical Wnt signals, we identified Axin as a protein that interacts with the intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of Wnt caused the translocation of Axin to the membrane and enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.

3T3 Cells↗
PubMed2001

The effect of high-pass filtering on TEOAE in 2-month-old infants.

The aim of the present study was to investigate the effect of high-pass filtering on TEOAE obtained from 2-month-old infants as a function of filter cut-off frequency, activity states and pass/fail status of infants. Two experiments were performed. In Experiment 1, 100 2-month-old infants (200 ears) in five activity states (asleep, awake but peaceful, sucking a pacifier, feeding, restless) were tested by use of TEOAE technology. Five different filter conditions were applied to the TEOAE responses post hoc. The filter conditions were set at 781 Hz (default setting), 1.0, 1.2, 1.4 and 1.6 kHz. Results from this experiment showed that TEOAE parameters such as whole-wave reproducibility (WR) and signal-to-noise ratio (SNR) at 0.8 kHz and 1.6 kHz, changed as a function of the cut-off frequency. The findings suggest that the 1.6 kHz and 1.2 kHz filter conditions are optimal for WR and SNR pass/fail criteria, respectively. Although all infant recordings appeared to benefit from the filtering, infants in the noisy states seemed to benefit the most. In Experiment 2, the high-pass filtering technique was applied to 23 infants (35 ears) who apparently failed the TEOAE tests on initial screening but were subsequently awarded a pass status based on the results from a follow-up auditory brainstem response (ABR) assessment. The findings showed a significant decrease in noise contamination of the TEOAE with a corresponding significant increase in WR. With high-pass filtering at 1.6 kHz, 21/35 ears could be reclassified into the pass category.

Acoustic Stimulation↗
PubMed2001

Physicians' and consumers' conflicting attitudes toward health care advertising.

The purpose of this paper is to explore the conflicting attitudes held by physicians and health care consumers toward health care advertising in an attempt to resolve the question. The paper introduces the differing positions held by the two groups. The rationale behind physicians' attitudes is then presented that advertising can be unethical, misleading, deceptive, and lead to unnecessary price increases. They believe that word-of-mouth does and should play the major role in attracting new patients. The opposite view of consumers is then presented which contends that health care advertising leads to higher consumer awareness of services, better services, promotes competitive pricing, and lowers rather than raises health care costs. The final section of the paper compares the arguments presented and concludes that health care advertising clearly has a place in the health care industry.

Advertising↗
PubMed2000

An Intermittent Star Formation History in a "Normal" Disk Galaxy: The Milky Way.

The star formation rate history of the Milky Way is derived using the chromospheric age distribution for 552 stars in the solar neighborhood. The stars' sample birth sites are distributed over a very large range of distances because of orbital diffusion and so give an estimate of the global star formation rate history. The derivation incorporates the metallicity dependence of chromospheric emission at a given age and corrections to account for incompleteness, scale height-age correlations, and stellar evolutionary effects. We find fluctuations in the global star formation rate with amplitudes greater than a factor of 2-3 on timescales less than 0.2-1 Gyr. The actual history is likely to be more bursty than found here because of the smearing effect of age uncertainties. There is some evidence for a slow secular increase in the star formation rate, perhaps a record of the accumulation history of our Galaxy. A smooth, nearly constant star formation rate history is strongly ruled out, confirming the result first discovered by Barry using a smaller sample and a different age calibration. This result suggests that galaxies can fluctuate coherently on large scales.

Journal Article↗
PubMed2000

Stratified mucin-producing intraepithelial lesions of the cervix: adenosquamous or columnar cell neoplasia?

BACKGROUND: Squamous (CIN) and glandular (ACIS) intraepithelial lesions often coexist in the same cervical specimen. However, a less common and little studied variant consists of a stratified epithelium resembling CIN in which conspicuous mucin production is present (Stratified Mucin-producing Intraepithelial LEsions (SMILE). This report describes the phenotypic characteristics of the SMILE, its associated lesions, and its immunophenotype. METHODS: Eighteen SMILEs were identified by the presence of conspicuous cytoplasmic clearing or vacuoles in lesions otherwise resembling CIN. The morphologic spectrum of SMILEs was detailed; including associated intraepithelial and invasive cervical neoplasms. In addition, selected cases were stained for mucicarmine, markers of squamous cell/reserve cell differentiation (keratin-14 and p63), and proliferative activity (Mib-1). RESULTS: Stratified neoplastic epithelial cells with a high Mib-1 index and a rounded or lobular contour at the epithelialstromal interface characterized SMILEs. In contrast to CIN, in which mucin droplets are confined to surface cells, mucin was present throughout the epithelium, varying from indistinct cytoplasmic clearing to discrete vacuoles. SMILEs were distinguished from benign metaplasia by nuclear hyperchromasia and a high Mib-1 index. All but three coexisted with either a squamous (CIN) or glandular (ACIS) precursor lesion. Nine of nine coexisting invasive carcinomas contained glandular, adenosquamous differentiation, or both. SMILEs stained negative for keratin-14 and variably for p63. When present, staining with p63 was confined to basal areas of SMILEs and was absent in areas of columnar differentiation. CONCLUSIONS: SMILEs are unusual cervical intraepithelial lesions best classified as variants of endocervical columnar cell neoplasia based on immunophenotype. The distribution and immunophenotype of SMILEs are consistent with a neoplasm arising in reserve cells in the transformation zone. The coexistence of a wide spectrum of intraepithelial and invasive cell phenotypes suggests that SMILEs are a marker for phenotypic instability, emphasizing the importance of identifying SMILEs and ensuring a complete examination of specimens containing this unusual precursor lesion.

Adenocarcinoma↗
PubMed2000

Rapid flow cytometric test for the diagnosis of membrane cytoskeleton-associated haemolytic anaemia.

The flow cytometric test measures the fluorescence intensity of intact red cells labelled with the dye eosin-5-maleimide, which reacts covalently with Lys-430 on the first extracellular loop of band 3 protein. In this study, red cells from patients with hereditary spherocytosis (HS), congenital dyserythropoietic anaemia type II, South-east Asian ovalocytosis and cryohydrocytosis have produced a greater degree of reduction of mean channel fluorescence readings than those for other patient groups and normal controls. The predictive value of this test for membrane abnormality was compared with the results obtained from the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method, which is currently the reference laboratory test for the identification of membrane protein deficiencies in hereditary spherocytosis and for the detection of spectrin variants in hereditary elliptocytosis. The dye method is a reliable, speedy diagnostic test (2 h from sample collection to result) for HS with a sensitivity of 92.7% and a specificity of 99.1%. Thus, it will serve well as a first-line screening test for the diagnosis of hereditary spherocytosis in routine haematology.

Adult↗
PubMed1999

Evaluation of a statewide non-name-based HIV surveillance system.

Recent advances in AIDS-related therapies have delayed the onset of AIDS-defining illnesses and reduced the usefulness of AIDS surveillance in assessing the incidence of early HIV disease and estimating future needs of the HIV-infected population. These changes have prompted renewed interest in expanding surveillance to include HIV and have engendered national debate on whether an HIV surveillance system should be based on reports of the names of infected individuals or employ non-name-based data codes. In 1994, the state of Maryland implemented a program to require HIV surveillance by unique identifier (UI) patient code. This evaluation of Maryland's program found that when complete, the 12-digit UI number provided a virtually unduplicated count 99.8% unique, was 99.9% unique with only the last four digits of the U.S. government Social Security Number (SSN), date of birth (DOB), and race, and 77.7% unique if the last four digits of the SSN were missing. Health care providers were willing to create the UI, with DOB and gender present 98.3% and 98.8% of the time, race was complete 84.1% and last four digits of SSN were complete 72.4%. The overall completeness of reporting for HIV tests was 87.8%.and 84.8%, respectively, using different methodologies. Evidence from the Maryland UI evaluation demonstrates that a non-name-based system can provide accurate, timely and valid data concerning the scope of the HIV epidemic, without the creation of state-wide name-based registry.

Acquired Immunodeficiency Syndrome↗
PubMed1999

New evidence to reconcile in vitro and epidemiologic data on the possible role of heroin on CD4+ decline among HIV-infected injecting drug users.

Long-term effects of drug type and other drug use related risk factors on CD4+ cell decline were assessed in 224 HIV-infected injecting drug users (IDUs) from Baltimore (ALIVE), USA, and 63 IDUs from Amsterdam, The Netherlands. Higher frequencies of borrowing used injection equipment since 1980 resulted in a higher CD4+ count already present before seroconversion (P = 0.049). Use of mainly heroin in the seroconversion interval resulted in a sharper CD4+ decline until the first 6 months after seroconversion (P = 0.004), but CD4+ values converged later on. This finding might reconcile earlier discordant epidemiological and laboratory study results regarding the possible effects of heroin.

Adult↗
PubMed1999

Effect of race on insurance coverage and health service use for HIV-infected gay men.

OBJECTIVE: To determine whether race is associated with health insurance coverage and health service use among gay and bisexual men in the Baltimore center of the Multicenter AIDS Cohort Study. METHODS: Data from eight semiannual study visits between 1991 and 1996 were used. Descriptive, stratified, and logistic regression analyses were conducted to determine whether race is associated with insurance coverage, medical, or dental service use, after controlling for socioeconomic variables. RESULTS: No difference was found between blacks' and whites' likelihood of having health insurance, private insurance, using inpatient, emergency department services, or antiretroviral medications. Whites were more likely to use outpatient services, particularly if CD4 cell counts were high, and were more likely to use dental services, although blacks were more likely to have dental insurance. CONCLUSIONS: Further research must be conducted to examine cultural, social, and psychological factors that help explain why white gay men use more outpatient and dental services, when other service use is unrelated to race. Investigators should be precise when using race as a variable in health services and epidemiologic research, emphasizing when racial differences truly exist versus when the variable race is a surrogate for another factor.

Adult↗
PubMed1999

Modulation of endocytic traffic in polarized Madin-Darby canine kidney cells by the small GTPase RhoA.

Efficient postendocytic membrane traffic in polarized epithelial cells is thought to be regulated in part by the actin cytoskeleton. RhoA modulates assemblies of actin in the cell, and it has been shown to regulate pinocytosis and phagocytosis; however, its effects on postendocytic traffic are largely unexplored. To this end, we expressed wild-type RhoA (RhoAWT), dominant active RhoA (RhoAV14), and dominant inactive RhoA (RhoAN19) in Madin-Darby canine kidney (MDCK) cells expressing the polymeric immunoglobulin receptor. RhoAV14 expression stimulated the rate of apical and basolateral endocytosis, whereas RhoAN19 expression decreased the rate from both membrane domains. Polarized basolateral recycling of transferrin was disrupted in RhoAV14-expressing cells as a result of increased ligand release at the apical pole of the cell. Degradation of basolaterally internalized epidermal growth factor was slowed in RhoAV14-expressing cells. Although apical recycling of immunoglobulin A (IgA) was largely unaffected in cells expressing RhoAV14, transcytosis of basolaterally internalized IgA was severely impaired. Morphological and biochemical analyses demonstrated that a large proportion of IgA internalized from the basolateral pole of RhoAV14-expressing cells remained within basolateral early endosomes and was slow to exit these compartments. RhoAN19 and RhoAWT expression had little effect on these postendocytic pathways. These results indicate that in polarized MDCK cells activated RhoA may modulate endocytosis from both membrane domains and postendocytic traffic at the basolateral pole of the cell.

3,3'-Diaminobenzidine↗