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Biomedical subjects

A O'Connell

Publications and source records attributed to A O'Connell.

At least 19 recordsLinked to original sources

Development of an integrated care pathway for the management of hemiplegic shoulder pain.

PURPOSE: To improve clinical management of patients with hemiplegic shoulder pain through development of an evidence-based multidisciplinary integrated care pathway (ICP), and to use this to audit quality of care against predefined standards. METHODS: The ICP was developed by a team of medical, paramedical and nursing staff. The evidence base was established through a systematic literature review supplemented by clinical consensus to ensure best practice where scientific evidence was lacking. Following development, performance was assessed against standards in a cohort of stroke patients with hemiplegia (n = 32) consecutively admitted to a regional unit providing in-patient rehabilitation for young patients with complex disabilities. RESULTS: Performance showed improvements in assessment and documentation of pain and in initial care, including analgesia and application of positioning/handling protocols. However, review and response to continuing or changing symptoms were poorly documented. Changes to the ICP were introduced to improve this. CONCLUSIONS: Principal benefits have been to raise awareness of shoulder pain, to educate staff and prompt management in line with recommended best practice, but strong leadership is essential to ensure continuity in clinical practice. Future research is needed to establish whether improved quality of care offsets the substantial investment of staff time in ICP development.

Adult↗

Epidemiological studies of human and animal Salmonella typhimurium DT104 and DT104b isolates in Ireland.

A total of 122 human and animal Salmonella Typhimurium DT104 isolates and 6 epidemiologically related DT104b isolates from human and animal products were analysed by pulsed-field gel electrophoresis (PFGE). Genomic DNA was subjected to macrorestriction with three enzymes, SpeI, SfiI and XbaI. A total of 14 restriction fragment length polymorphism (RFLP) profiles were identified when the PFGE patterns from the three enzymes were combined. The majority of isolates (81.2%) exhibited the same RFLP profile. Six animal DT104 isolates, susceptible to enrofloxacin and resistant to naladixic acid, were identified from the antibiotic susceptibility test. Four of these isolates had a different PFGE profile from the common RFLP. In addition, 4 of the 6 isolates were geographically clustered in one region. It was concluded that there was one predominant strain of S. Typhimurium DT104 in Ireland and that the potential and selection pressures for emergence of fluoroquinolone-resistant isolates were present.

Animals↗

Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe.

2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn-VPA (16-85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl-4-yn-VPA also influenced memory consolidation processes as, when given at 3 h post-passive avoidance training, the amnesia induced by scopolamine given 6 h post-training was prevented in a dose-dependent manner. Chronic administration of pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition-enhancing qualities of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.

Aging↗

Factors related to self-efficacy for use of condoms and birth control among women at risk for HIV infection.

Many women who are at risk for HIV do not regularly use condoms, particularly with their main partners. In this paper we examine factors related to self-efficacy for condom use with main and other partners and self-efficacy for birth control in 2864 women interviewed in five urban high-risk communities. Limited social and economic resources, dependence on a main partner, and risk factors, including exchanging sex for money or drugs and binge drinking, were found to be negatively related to self-efficacy. Segmentation analysis identified groups of women with low self-efficacy who should be the focus of preventive interventions.

Adolescent↗

Growth and paracrine factors regulating follicular formation and cellular function.

The purpose of this paper is to review, using fetal sheep as the animal model, aspects of ovarian development related to follicular formation and to report on the identity of growth and paracrine factors which might be involved in this process. Before follicular formation there is a massive and sustained colonisation of the fetal ovary by mesonephric cells, which become a precursor source of follicular cells. From within the ovarian medulla, somatic 'cell-streams' branch into the cortex around nests of oogonia and oocytes. These 'cell-streams', which contain elongated cells with either flattened or cuboidal shaped nuclei, express steroidogenic factor-1 (SF-1), steroid acute regulatory protein (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450(scc), and P450(aromatase) mRNA and/or protein. Follicles form from the association of an oocyte with the 'cell-stream' with either a single layer of flattened cells (i.e. type 1 follicle) or with a mixture of flattened and cuboidal cells (i.e. type 1a follicle). These newly-formed follicles have between 3 and 57 somatic cells (i.e. granulosa cells) and contain oocytes which vary in diameter between 23 and 52 microm. Newly formed and early growing follicles have been identified with growth factors or growth factor receptors in either the oocytes or granulosa cells. Many of the growth factors are from the TGFbeta superfamily and are expressed in a cell- and stage-specific manner.

Animals↗

Critical influenza virus infection.

OBJECTIVE: To determine the risk of death from influenza infection in children with chronic underlying disease. METHODOLOGY: An 18-year retrospective study of children with 'critical' influenza A or B virus infection, defined as requiring admission to intensive care or resulting in death, but excluding laryngotracheobronchitis (LTB). Influenza infection was diagnosed by viral culture and/or immunofluorescence of respiratory secretions. Patients with LTB were analysed separately. RESULTS: There were 27 cases of critical influenza virus infection over the study period, comprising 26 admissions to the intensive care unit (excluding LTB) and one death on the general wards. Thirteen (48%) of the 27 children had chronic underlying disease. In addition, 12 children with LTB were admitted to the intensive care unit. The LTB children were older and less likely to have chronic underlying disease. Nosocomial infection caused seven (26%) of the 27 critical infections. Nine (33%) of the 27 children with critical influenza died. Six (46%) of 13 children with chronic underlying disease and influenza admitted to intensive care died, compared with three of 14 (21%) without any underlying disease (odds ratio = 3.1, 95% confidence interval 0.6-14.0). CONCLUSIONS: Critical life-threatening influenza virus infection was uncommon, but the mortality was high (33%), particularly in children with chronic underlying disease. Nosocomial infection with influenza was an important cause of admission to intensive care.

Bronchitis↗

Improved outcomes of children with malignancy admitted to a pediatric intensive care unit.

OBJECTIVE: To assess the acute and long-term outcomes of children admitted to the intensive care unit with cancer or complications after bone marrow transplantation. DESIGN: Retrospective analysis of databases from a prospective pediatric intensive care unit (PICU) database supplemented by case notes review. SETTING: A PICU in a tertiary pediatric hospital. PATIENTS: All children with malignancy admitted to the PICU between May 1, 1987, and April 30, 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 206 admissions to the PICU during a 9-yr study period of 150 children with malignancies or complications after bone marrow transplantation. Forty patents died in the PICU (27% mortality rate). The most frequent indications for PICU admission were shock and respiratory disease. Of 56 children admitted with shock, there were 16 deaths (29% mortality rate). In 24 episodes of sepsis, inotropic and ventilatory support were required and 13 patients (54%) survived. Analysis of long-term survival gave estimates of 50% survival for all oncology patients admitted to the PICU and 42% for those admitted for shock. CONCLUSIONS: A high proportion of oncology patients admitted to the PICU requiring intensive intervention survive and go on to be cured of their malignancy. Our study suggests the PICU outcome for these patients has improved.

Adolescent↗

Oral manifestations of primary immunological diseases.

BACKGROUND: Primary immunodeficiencies have many oral manifestations. The clinical presentation of these diseases demonstrates the roles of different immune cells for the maintenance of oral health. METHODS: The authors reviewed selected literature describing systemic and oral manifestations of the primary immunodeficiencies published between 1966 and 1999. RESULTS: The authors found that oral candidiasis and herpetic infections are seen frequently in patients with T-cell deficiencies, while patients with B-cell deficiencies are most susceptible to bacterial infections. Periodontitis and oral candidiasis are found in some, but not all, phagocyte deficiencies. CONCLUSIONS: These findings demonstrate that T cells, B cells and phagocytes all have roles in oral immunity. CLINICAL IMPLICATIONS: Acquired conditions that affect the immune system such as diabetes, alcoholism and acquired immunodeficiency syndrome, as well as certain medications, will affect oral defense mechanisms. The effects that acquired immunodeficiencies will have on oral health can be predicted from the oral manifestations of primary immunodeficiencies.

B-Lymphocytes↗

The referral process and urban health care in sub-Saharan Africa: the case of Lusaka, Zambia.

Much of the current reform of urban health systems in sub-Saharan Africa focuses upon the referral system between different levels of care. It is often assumed that patients are by-passing primary facilities which leads to congestion at hospital outpatient departments. Zambia is well advanced in its health sector reform and this case study from the capital, Lusaka, explores the patterns of health seeking behaviour of the urban population, the reasons behind health care choices, the functioning of the referral system and the users' evaluations of the care received. Data were collected across three levels of the system: the community, local health centres and the main hospital (both in- and out-patients). Results showed those who by-passed health centres were doing so because they believed the hospital outpatient department to be cheaper and/or better supplied with drugs (not because they believed they would receive better technical care). Few users were given information about their diagnosis or reason for referral. The most striking result was the degree of unmet need for health services and the large number of individuals who were self-medicating due to lack of money rather than the minor nature of their illness. The current upgrading of urban health centres into 'reference centres' may provide a capacity for unmet need rather than decongesting the hospital outpatient department as originally intended.

Adolescent↗

Oral rehabilitation of a child with primary failure of tooth eruption.

This article describes the prosthetic evaluation and treatment of a 10-year-old female patient with primary failure of tooth eruption. This case is unique in that the failure of eruption affected both the deciduous and permanent dentition in all quadrants, in the absence of any other systemic abnormalities. After diagnostic articulation and a thorough discussion of the treatment with the patient and her parents, complete maxillary and mandibular overdentures were fabricated. The process followed with this preadolescent patient to ensure maximum compliance, success, and encouragement toward a positive attitude in wearing complete dentures is reported.

Child↗

Molecular analysis of Pseudomonas aeruginosa: epidemiological investigation of mastitis outbreaks in Irish dairy herds.

Pseudomonas aeruginosa is a pathogen in both humans and animals. This bacterium, most often associated with respiratory infections in cystic fibrosis patients, was found to be the causative agent in bovine mastitis outbreaks among 11 Irish dairy herds. Epidemiological findings suggested that the infection was spread to all herds by teat wipes that had been contaminated with this organism. Two molecular-typing strategies were used in an attempt to determine the genomic relationship(s), if any, of the P. aeruginosa strains isolated from the various herds and to verify whether the same strain was responsible for each outbreak. Thirty-six isolates from the mastitis outbreaks were tested and compared to fourteen clinical isolates from Cork University Hospital. With one exception, all outbreak-linked strains produced identical patterns when ribotyped with ClaI and PvuII enzymes. Eight of the clinical isolates gave the same ClaI ribotype pattern as the mastitis-causing strains. However, PvuII proved more discriminatory, with only the outbreak isolates producing identical patterns. Similar results were obtained with RW3A-primed DNA amplification fingerprinting, with all outbreak isolates except one displaying the same fingerprint array. The clinical strains produced several fingerprint patterns, all of which were different from those of the mastitis-causing isolates. Fine-resolution DNA fingerprinting with a fluorescence-labelled RW3A primer also identified a number of low-molecular-weight polymorphisms that would have remained undetected by conventional methods. These data support the view that the same P. aeruginosa strain was responsible for the mastitis outbreaks in all 11 herds.

Animals↗

Populations of granulosa cells in small follicles of the sheep ovary.

The aim of this study in sheep ovaries was to determine the total number of granulosa cells in primordial follicles and at subsequent stages of growth to early antrum formation. The second aim was to examine the interrelationships among the total number of granulosa cells in the follicles, the number of granulosa cells in the section through the oocyte nucleolus, and the diameter of the oocyte. A third aim was to examine whether proliferating cell nuclear antigen labelling occurred in flattened granulosa cells in primordial follicles or was confined to follicles containing cuboidal granulosa cells. The follicles were classified using the section through the oocyte nucleolus by the configuration of granulosa cells around the oocyte as type 1 (primordial), type 1a (transitory), type 2 (primary), type 3 (small preantral), type 4 (large preantral), and type 5 (small antral). In type 1 follicles, the number of granulosa cells and oocyte diameter were highly variable in both fetal and adult ovaries. Each type of follicle was significantly different from the others (all P < 0.05) with respect to oocyte diameter, number of granulosa cells in the section through the oocyte nucleolus and total number of granulosa cells. Follicles classified as type 2, 3, 4 or 5 each corresponded to two doublings of the total granulosa cell population. The relationships between oocyte diameter and the number of granulosa cells (that is, in the section through the oocyte nucleous or total population per follicle) could all be described by the regression equation loge chi = a + b loge gamma with the correlation coefficients R always > 0.93. For each pair of variables the slopes (b) for each type of follicle were not different from the overall slope for all types of follicle pooled. Immunostaining for proliferating cell nuclear antigen was observed in granulosa cells in type 1 follicles, as well as in the other types of follicle. These findings indicate that 'flattened' granulosa cells in type 1 follicles express an essential nuclear protein involved in cell proliferation before assuming the cuboidal shape. Thus, when considering factors that regulate specific phases of early follicular growth, it is important to consider: (i) the follicle classification system used; (ii) the animal model studied; (iii) whether type 1 follicles are all quiescent; and (iv) the likelihood that each follicle type represents more than one doubling of the population of granulosa cells.

Animals↗

Control of early ovarian follicular development.

Early follicular growth refers to the development of an ovarian follicle from the primordial to early antral phase. In sheep and cows these phases of growth can be classified by the configuration of granulosal cells in the largest cross-section of the follicle as types 1 (primordial), 1a (transitory) 2 (primary), 3 and 4 (preantral) and 5 (early antral). Follicles classified as type 1 may be highly variable within each species with respect to number of granulosal cells and diameter of oocyte. Much of the variation in granulosal cell composition of type 1 follicles may occur at formation and this may account for the variability in granulosal cell composition throughout subsequent stages of growth. There appear to be important differences among species (for example sheep and cattle) in the number and function of granulosal cells relative to the diameter of the oocyte during the initiation of follicular growth. There is evidence that most, if not all, of the growth phases from types 1 to 5 are gonadotrophin-independent and that follicles develop in a hierarchical manner. In sheep, cows and pigs, numerous growth factor, growth factor receptor and gonadotrophin receptor mRNAs and peptides (for example c-kit, stem cell factor, GDF-9, beta B and beta A activin/inhibin subunit, alpha inhibin subunit, follistatin, FGF-2, EGF, EGF-R, TGF beta 1,2 and 3 FSH-R and LH-R) are expressed in a phase of growth (for example types 1-5)-specific and cell-specific manner. However, the roles of many of these factors remain to be determined.

Animals↗

Ca2+-dependent inactivation of a store-operated Ca2+ current in human submandibular gland cells. Role of a staurosporine-sensitive protein kinase and the intracellular Ca2+ pump.

Stimulation of human submandibular gland cells with carbachol, inositol trisphosphate (IP3), thapsigargin, or tert-butylhydroxyquinone induced an inward current that was sensitive to external Ca2+ concentration ([Ca2+]e) and was also carried by external Na+ or Ba2+ (in a Ca2+-free medium) with amplitudes in the order Ca2+ > Ba2+ > Na+. All cation currents were blocked by La3+ and Gd3+ but not by Zn2+. The IP3-stimulated current with 10 microM 3-deoxy-3-fluoro-D-myo-inositol 1,4,5-triphosphate and 10 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in the pipette solution, showed 50% inactivation in <5 min and >5 min with 10 and 1 mM [Ca2+]e, respectively. The Na+ current was not inactivated, whereas the Ba2+ current inactivated at a slower rate. The protein kinase inhibitor, staurosporine, delayed the inactivation and increased the amplitude of the current, whereas the protein Ser/Thr phosphatase inhibitor, calyculin A, reduced the current. Thapsigargin- and tert-butylhydroxyquinone-stimulated Ca2+ currents inactivated faster. Importantly, these agents accelerated the inactivation of the IP3-stimulated current. The data demonstrate that internal Ca2+ store depletion-activated Ca2+ current (ISOC) in this salivary cell line is regulated by a Ca2+-dependent feedback mechanism involving a staurosporine-sensitive protein kinase and the intracellular Ca2+ pump. We suggest that the Ca2+ pump modulates ISOC by regulating [Ca2+]i in the region of Ca2+ influx.

Calcium↗

Crystalloids, colloids and kids: a review of paediatric burns in intensive care.

This is a retrospective review of all burns patients admitted to a paediatric intensive care unit (PICU) over a 7 year period. Resuscitation fluid therapy and clinical course are presented. Ninety-eight new burns victims were admitted with a mortality rate of 10.2%, all in burns of greater than 25% body surface area (BSA). The incidence of ARDS was 20%, with an 18% mortality rate. Of 85 patients with burns greater than 5% BSA, 33 received the hospital-recommended colloid-based resuscitation formula, 46 received a combination of crystalloids and colloids and in 6 patients the resuscitation regimen was not able to be determined. The aetiology, age distribution, sex ratio, severity of burns and length of stay in hospital did not alter significantly over the study period. The number of burns admissions to PICU increased, as did their duration of intubation and ICU stay. The hospital-recommended resuscitation formula consistently underestimated the fluid volume required for adequate resuscitation. No statistically significant difference in adverse effects was found between the resuscitation groups. This study is unable to recommend a definitive approach to the fluid resuscitation of burns shock in paediatrics and the best approach is one of meticulous fluid resuscitation titrated on clinical effect.

Adolescent↗

Steroid contents of and steroidogenesis in vitro by the developing gonad and mesonephros around sexual differentiation in fetal sheep.

The aim of the present study was to establish whether the steroids, progesterone, androstenedione, testosterone and oestradiol, were present in the mesonephric-gonadal complex of female and male sheep fetuses around sexual differentiation (that is, from day 28 to day 45 of gestation, with sexual differentiation occurring at approximately day 32). A second aim was to test whether the mesonephric-gonadal complex, mesonephros (days 35-45 only) and gonad (days 35-45 only) were capable of steroid synthesis in vitro. The steroid contents in the mesonephric-gonadal complex were not detectable before sexual differentiation. However, from day 35 of gestation onwards, the mesonephric-ovarian complex contained mainly oestradiol and the mesonephric-testicular complex contained mainly testosterone: from day 35 until day 45 the increase in content of these two steroids exceeded the increase in the mass of tissue by more than fivefold. From day 40 to day 45 of gestation, the contents of the other steroids in the pathways to oestradiol increased progressively in both sexes but more in parallel with the increase in tissue mass. In contrast to the steroid contents in the tissue at recovery, the mesonephric-gonadal tissue from both sexes in tissue culture was able to synthesize most steroids before and after sexual differentiation and also to metabolise supplementary androstenedione to oestradiol. These findings suggest that many, if not all, of the steroidogenic enzymes in the pathway from cholesterol to oestradiol are present before sexual differentiation. Most of the aforementioned steroids were present in detectable amounts in isolated mesonephros and gonad of both sexes after sexual differentiation. Moreover, for both the isolated mesonephros and gonad, there were increases in the mean contents of most steroids after culture relative to the contents in the tissues at recovery. These data suggest that the mesonephros, as well as the gonad, in both sexes is capable of synthesizing steroid. It is concluded that, in the sheep fetus, the female and male gonads are steroidogenically active after sexual differentiation, that the steroidogenic enzymes develop before sexual differentiation, and that the mesonephros is a site of steroid synthesis.

Androstenedione↗

Heparin absorption across the intestine: effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal instillations and in Caco-2 monolayers.

PURPOSE: The effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on heparin intestinal absorption were studied using rat in situ ileal and colonic instillations and Caco-2 monolayers. METHODS: The flux of heparin was tested in the following groups: i) heparin alone, ii) heparin in the presence of SNAC, iii) heparin in the presence of propylene glycol (PG), and iv) heparin in the presence of SNAC and PG. Heparin absorption was measured by the APTT assay in the in situ models and by the anti-Factor Xa assay in Caco-2. SNAC and [3H]-SNAC fluxes were assessed by HPLC and by scintillation counting respectively. RESULTS: In the rat ileal and colonic in situ instillations SNAC (17-35 mg) promoted heparin absorption in the presence and absence of PG without damaging the tissue. PG alone did not alter heparin absorption in situ, but it amplified the effect of SNAC. In Caco-2, enhanced heparin fluxes were variable in the presence of non-cytotoxic concentrations of SNAC (< 10 mg/ml) and these effects could not be discriminated from those of PG. Papp values for SNAC alone were 2.2 x 10(-5) cm/s and 2.0 x 10(-5) cm/s in the mucosal-to-serosal and serosal-to-mucosal directions respectively, suggesting a substantial passive transcellular flux. Transport of SNAC was significantly reduced in the presence of heparin and/or PG, perhaps indicating physical association between the agents. CONCLUSIONS: SNAC augmented heparin absorption alone and in combination with PG in the rat in situ models without causing toxicity. Caco-2 had limitations for testing increased heparin absorption due to cytotoxic effects of high concentrations of SNAC and PG. However, SNAC itself was well absorbed across Caco-2 and its mechanism of permeation was determined.

Animals↗