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Biomedical subjects

C Dunne

Publications and source records attributed to C Dunne.

At least 19 recordsLinked to original sources

Two sets of HLA Class II DRB and DQB1 alleles co-segregate among family members in a single maternal haplotype.

HLA class II typing by sequence specific oligonucleotide probes (SSOP) on the family of a Burkit's Lymphoma patient produced hybridization patterns indicating the presence of two DRB1, and two linked DQB1 genes on the same maternal chromosome. DRB and DQB1 exon 2 amplification products associated with the novel maternal haplotype were identified by DNA typing techniques: These products corresponded to DRB1*0101, DRB1*1501, DRB5*01, DQB1*0501 and DQB1*0602 alleles. These alleles were seen to co-segregate among siblings sharing the same maternal haplotype. The patient, his mother and two of his siblings each appeared to possess elements of three DRB1, DQA1 and DQB1 genes. HLA DNA typing results indicated that a DNA sequence of approximately 100 Kb, spanning the region between, and including, DRB1 and DQB1 genes was inserted into the maternal haplotype. Serological typing on EBV transformed B lymphocytes obtained from the patient's mother showed three expressed DRB1 antigens. Serology on EBV transformed patient's cells also indicated multiple DRB1 antigen expression. The expression of three DRB1 and DQB1 genes on the cells of this patient would make it virtually impossible to obtain a suitably matched unrelated stem cell donor.

Alleles↗

Identification and nucleotide sequence of a new null allele, HLA B*3540N.

We report the definition of an HLA class I null allele that has been identified within the B35 group by a combination of serological and molecular typing. This allele, which has been named B*3540N, was detected in a French, potential unrelated hematopoietic stem cell donor of unknown ethnic origin, selected as a probable match for an Irish patient. The presence of the null allele was initially determined by the absence of B35 reactivity by serological typing, in contrast to positive reactions by PCR-SSP and PCR-SSO typing. Subsequent sequencing of clones containing the full genomic sequence of the B*35 allele identified a single nucleotide deletion within exon 4 which resulted in the introduction of a stop codon downstream within exon 4.

Alleles↗

Glucocorticoid epidural for sciatica: metabolic and endocrine sequelae.

OBJECTIVE: The study was designed to investigate the effect of epidural administration of glucocorticoid on insulin sensitivity. METHODS: Ten healthy individuals with sciatica underwent a short insulin tolerance test before and twice following (at 24 h and 1 week) a caudal epidural containing 80 mg triamcinolone. Fasting glucose, insulin and cortisol concentrations were also measured. RESULTS: The rate of glucose disappearance after insulin administration (k(ITT)) fell from 3.6%/min before the epidural to 1.9%/min 24 h afterwards (P=0.001) and returned to pretreatment values by 1 week. Significantly raised fasting insulin and glucose levels also reflected impaired insulin sensitivity immediately after the epidural. Morning cortisol levels were suppressed after the epidural (49 nmol/l at 24 h and 95 nmol/l at 1 week vs 352 nmol/l at baseline; P<0.01). CONCLUSIONS: Epidural administration of glucocorticoid results in potent suppression of insulin action and this should be taken into account when patients with diabetes require treatment for sciatica.

Adult↗

In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings.

The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.

Animals↗

Adaptation of bacteria to the intestinal niche: probiotics and gut disorder.

The gastrointestinal tract is a complex ecosystem host to a diverse and highly evolved microbial community composed of hundreds of different microbial species. The interactions that occur between this complex microbial community and the human host have become the focus of scientific research due to increases in the incidence of illnesses associated with deficient or compromised microflora (e.g., gastrointestinal tract infections, inflammatory bowel disease (Crohn's disease and ulcerative colitis), irritable bowel syndrome, antibiotic-induced diarrhea, constipation, food allergies, cardiovascular disease, and certain cancers). Effective multidisciplinary research programs now complement conventional microbiology with molecular ecology techniques to provide culture-independent analysis of the gastrointestinal ecosystem. Furthermore, as we acquire an understanding of gut microflora composition and processes such as intestinal adherence, colonization, translocation, and immunomodulation, we are also elucidating mechanisms by which these can be influenced. This knowledge not only allows scientists to define the activities and interactions of "functional food"-borne beneficial bacteria in the gut, but will also provide the scientific basis for the development of innovative biotechnology-based products tailored to prevent specific diseases and promote overall human gastrointestinal health.

Bacterial Physiological Phenomena↗

Reference strand mediated conformation analysis resolves HLA-DRB1 typing ambiguities when matching for unrelated bone marrow transplantation.

We show here the use of reference strand mediated conformation analysis (RSCA) to unambiguously resolve the HLA-DRB1 typing of two individuals which were selected as potential unrelated donors for bone marrow transplantation (BMT). In the first case, both sequence-specific primer (SSP) amplification and sequence-specific oligonucleotide probing (SSO), routinely used in different tissue typing laboratories gave, for the two unrelated donors, the same ambiguous typing of HLA-DRB1*04011+*0403 or DRB1*0407+*0413. In this case sequence-based typing (SBT) was not the method of choice to resolve the situation, due to the sequence ambiguities of these two given combinations. RSCA of both samples, using homozygous typing cells (HTCs) for DRB1*04011, *0403 and *0407 as internal controls, gave the unambiguous result that both donors were HLA-DRB1*04011+*0403. In the second case, a donor was typed as DRB1*1102+1103 by SSP, while SSO excluded the DRB1*1102 allele. The patient was unambiguously typed as DRB1*1101+1103 by both techniques. RSCA, using DNA from reference cell lines as internal controls, gave the unambiguous typing that the donor was DRB1*1103 homozygous.

Alleles↗

Acute testing of the rate-smoothed pacing algorithm for ventricular rate stabilization.

We evaluated the capability of a new pacemaker-based rate-smoothing algorithm (RSA) to reduce the irregular ventricular response of AF. RSA prevents sudden decreases in rate using a modified physiological band and flywheel feature. Twelve patients (51 +/- 21 years) with hemodynamically tolerated AF of 4 months to 20 years duration were studied. Atrial and ventricular leads were connected to the external pacemaker device in the electrophysiology laboratory. Consecutive RR intervals during AF were measured at baseline and after ventricular pacing with RSA ON. Ventricular pacing with the rate smoothing algorithm reduced maximum RR intervals (1,207 +/- 299 vs 855 +/- 148 ms, P = 0.0005), with no significant change in the minimum RR interval (401 +/- 55 vs 393 +/- 74 ms, P = 0.292). A small shortening of the mean RR interval (634 +/- 153 vs 594 +/- 135 ms, P = 0.007) was seen with no change in the median RR interval (609 +/- 153 vs 595 +/- 143 ms, P = 0.388). There was a 43% reduction in RR standard deviation (145 +/- 52 vs 82 +/- 28, P = 0.0005), 49% reduction in mean absolute RR interval difference (MAD) (152 +/- 64 vs 77 +/- 34, P = 0.0005) and MAD/mean RR ratio (0.23 +/- 0.05 vs 0.13 +/- 0.04, P = 0.0005). We conclude that rate-smoothed pacing effectively reduces RR variability of AF in the acute setting.

Adult↗

Validation of a noninvasive measure of local myocardial repolarization in a conscious human model: adaptation of repolarization to changes in rate.

INTRODUCTION: A commercial pacemaker sensor measure of the unipolar endocardial stimulus to T wave interval may accurately reflect changes in the monophasic action potential duration at 90% repolarization (APD90). This sensor system was used to study the kinetics of adaptation of repolarization duration to changes in heart rate in humans. METHODS AND RESULTS: Patients were studied using an external pacemaker capable of displaying all stimulus to T wave intervals for each paced beat. Right ventricular stimulation was delivered via the pacemaker and compared simultaneously to APD90. Steady-state pacing was simulated by 60 seconds of pacing at cycle lengths (CLs) 350 to 700 msec. Adaptation to a new ventricular rate was analyzed with a sudden 200-msec decrease in CL. The relation between repolarization measure and steady-state CL (n = 16) was linear with a slope of 0.16 and 0.19 for APD90 and stimulus to T wave interval, respectively (P = NS). The adaptation of both repolarization measures to a sudden change in rate were best modeled by a biexponential function. Stimulus to T wave interval exhibited a parallel course to APD90, and an analysis of normalized differences between APD90 and stimulus to T wave interval followed an approximately normal distribution, with 93.5% of the paired differences within 2 SD of the mean. CONCLUSION: A pacemaker sensor measure of stimulus to T wave interval accurately parallels APD90 during both steady-state and sudden changes in rate. Repolarization in human endocardium follows a linear relation to steady-state CL and adapts to a new rate with a biexponential function. This model represents a novel method for studying human cardiac repolarization.

Action Potentials↗

Effects of sensor selection on exercise stroke volume in pacemaker dependent patients.

The effects of sensor selection and sensor blending on the cardiovascular response to graded exercise was evaluated in 10 patients (age 74 +/- 2 yrs; 7 men and 3 women) implanted with a dual sensor rate adaptive VVIR pacemaker (Vitatron Topaz model 515). Patients underwent three graded exercise tests (GXT) with sensor programming randomly assigned. For a given graded exercise text the pacemaker was programmed into activity sensing (ACT), QT sensing, or dual sensing (ACT = QT). Data were recorded at rest and during each stage of the graded exercise text. Oxygen uptake (VO2) was measured continuously using a Q Plex I system. Heart rate (HR), stroke volume (SV), and cardiac output (Qc) were measured by impedance cardiography. Systolic time intervals were calculated from simultaneous recordings of the ECG, phonocardiogram, and the impedance cardiogram. In response to the GXT no differences in peak VO2 were observed across the three sensor settings. Regardless of the sensor setting Qc increased linearly with each increment in VO2. The HR response to ACT only pacing was significantly higher than in the other two pacing conditions. During ACT only pacing SV failed to rise in response to exercise. The increased exercise Qc during QT and ACT = QT pacing were mediated by significant increases in both HR and SV. The QT and dual pacing conditions were also associated with longer diastolic filling times. The data indicate that the mechanisms responsible for the increase Qc during exercise were different for ACT versus ACT = QT or QT sensor-driven pacing.

Aged↗

Lethal autonomy: the malfunction of the informed consent mechanism within the context of prenatal diagnosis of genetic variants.

In this article, Cara Dunne and Catherine Warren challenge the current role of genetic counselors in advising expectant mothers about potential genetic defects of their fetuses. They show that genetic counselors sometimes provide one-sided negative information to women undergoing prenatal diagnosis of genetic variants. This biased information promotes abortion of what are considered "defective" fetuses. The misleading information provided by the genetic counselors and the termination of the pregnancies is akin to the eugenics movement. The authors describe the early 20th century eugenics movement, explore the origin and development of the Human Genome Project, analyze the current role of genetic counseling, and explain the importance of the informed consent process to the exercise of autonomy. Dunne and Warren conclude by offering methods by which to restructure the informed consent mechanism to offer a more balanced assessment of the risks and benefits associated with genetic disability.

Abortion, Eugenic↗

Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis.

Neural stem cells in the lateral ventricles of the adult mouse CNS participate in repopulation of forebrain structures in vivo and are amenable to in vitro expansion by epidermal growth factor (EGF). There have been no reports of stem cells in more caudal brain regions or in the spinal cord of adult mammals. In this study we found that although ineffective alone, EGF and basic fibroblast growth factor (bFGF) cooperated to induce the proliferation, self-renewal, and expansion of neural stem cells isolated from the adult mouse thoracic spinal cord. The proliferating stem cells, in both primary culture and secondary expanded clones, formed spheres of undifferentiated cells that were induced to differentiate into neurons, astrocytes, and oligodendrocytes. Neural stem cells, whose proliferation was dependent on EGF+bFGF, were also isolated from the lumbar/sacral segment of the spinal cord as well as the third and fourth ventricles (but not adjacent brain parenchyma). Although all of the stem cells examined were similarly multipotent and expandable, quantitative analyses demonstrated that the lateral ventricles (EGF-dependent) and lumbar/sacral spinal cord (EGF+bFGF-dependent) yielded the greatest number of these cells. Thus, the spinal cord and the entire ventricular neuroaxis of the adult mammalian CNS contain multipotent stem cells, present at variable frequency and with unique in vitro activation requirements.

Animals↗

Multimycotoxin detection and clean-up method for aflatoxins, ochratoxin and zearalenone in animal feed ingredients using high-performance liquid chromatography and gel permeation chromatography.

A sensitive and reliable method is described for the determination of aflatoxins B1, B2, G1 and G2, ochratoxin A and zearalenone in animal feed ingredients. A multi-toxin extraction and clean-up procedure is used, with dichloromethane-1 M hydrochloric acid (10:1) being used for the extraction and gel permeation chromatography being used for the clean-up. The liquid chromatographic method developed for the separation of the six mycotoxins involves gradient elution with a reversed-phase C18 column and fluorescence detection. Recoveries, repeatability and reproducibility have been determined on maize, palm and wheat. The detection limits varied depending on the type of feed.

Aflatoxins↗

The sports' clinic: a one year review of new referrals.

The new presentations to the Cork Sports' Clinic over a one year period 1.1.90 to 31.12.90 were examined. We looked at the age and sex distribution of the presenting population, the type and site of injury, the sport played and the treatment and outcome of the injury. 126 new cases presented in 1990. 107 (85%) were male. The three commonest sports featured were all contact ones. The knee was the commonest site of injury (46.8% of cases) with 73.1% of injuries occurring in the lower limb. 73% of cases presented between the ages of 15 to 29 years. The majority of patients had improved on follow-up. Nine were referred to an orthopaedic service-five fractures and four serious ligamental injuries. The Cork Sports' Clinic works adjacent to a busy accident and emergency department. There is a definite need for our clinic in conjunction with the casualty department.

Adolescent↗

Hyperthyroidism associated with acute suppurative thyroiditis.

Acute suppurative thyroiditis is a rare condition with potentially serious complications. It has been suggested that hyperthyroidism may be a feature in occasional cases but this has been poorly documented. We describe a patient in whom acute suppurative thyroiditis caused transient hyperthyroidism.

Acute Disease↗

Extra meetings: a tool for decisions and therapy.

An Adolescent Unit uses the tool of any member of staff or patient group having the right to call a meeting. The development of this idea, anxieties about it, its usefulness and examples are presented. The meetings are used for communication, support or decisions and are often in themselves the vehicles for change.

Adolescent↗