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Biomedical subjects

L Cullen

Publications and source records attributed to L Cullen.

At least 19 recordsLinked to original sources
PubMed2005

Overweight and obesity in Irish primary schools: retrospective cohort study.

BACKGROUND: This retrospective cohort study investigates the feasibility of using established methods and routinely generated data from the statutory primary school health-screening programme to estimate prevalence rates for childhood overweight and obesity in children from a rural area in the Republic of Ireland (ROI). METHOD: Paper-based records in the primary school health service for County Leitrim and parts of County Cavan in north-west of ROI were hand searched to identify children attending senior infant classes during academic year 2001/2002. Electronic calculation of body mass index (BMI) and age at examination was carried out. Application of age- and sex-specific cut-off points from International Obesity Task Force (IOTF) and United Kingdom (UK) standard definitions for childhood overweight and obesity was used to determine age- and sex-specific prevalence rates for childhood overweight and obesity. RESULTS: The eligible cohort was almost completely identified and consisted of 361 children. Weight and height measurements were available on 328 (91%) children aged between 4.22 and 7.92 years. IOTF standard application gave prevalence rates of 25% for obesity and overweight in boys and 26% in girls. With the UK growth standard, this increased to 34% in boys and reduced to 23% in girls. CONCLUSION: It is feasible to generate prevalence rates for childhood overweight and obesity from data routinely obtained through the statutory school health-screening programme in ROI. This study suggests levels of childhood overweight and obesity comparable to other Western societies. Further research on developing a universally accepted standard definition of childhood overweight and obesity is required.

Body Height↗
PubMed2003

Effect of H. pylori infection on the expression of cyclooxygenase-2 in human gastric mucosa.

Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE(2) and PGI(2)) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H. pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa. Prostaglandin (PGE(2)) and prostacyclin (PGI(2)) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H. pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry. In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE(2) and PGI(2) were seen in patients infected with H. pylori (191+/-30 and 245+/-88ng/mg protein, respectively) compared with non-infected patients (77+/-17 and 120+/-36ng/mg protein, respectively). There was significant inhibition of PGE(2) and PGI(2) with aspirin in both H. pylori infected (28+/-6.6 and 53+/-43ng/mg, respectively) and in non-infected patients (16+/-7 and 12.5+/-3.5ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2.Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp-infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE(2) in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated.

6-Ketoprostaglandin F1 alpha↗
PubMed2002

Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9.

We have generated rat monoclonal antibodies that specifically recognise caspase-2 from many species, including mouse, rat and humans. Using these antibodies, we have investigated caspase-2 expression, subcellular localisation and processing. We demonstrate that caspase-2 is expressed in most tissues and cell types. Cell fractionation and immunohistochemistry experiments show that caspase-2 is found in the nuclear and cytosolic fractions, including a significant portion present in the Golgi complex. We found that caspase-2 is processed in response to many apoptotic stimuli but experiments with caspase-2 deficient mice demonstrated that it is not required for apoptosis of thymocytes or dorsal root ganglia (DRG) neurons in response to a variety of cytotoxic stimuli. Caspase-2 processing does not occur in thymocytes lacking Apaf-1 or caspase-9, suggesting that in this cell type, activation of caspase-2 occurs downstream of apoptosome formation.

Animals↗
PubMed2001

Normobaric hyperoxic stress in budgerigars: enzymic antioxidants and lipid peroxidation.

The effects of acute (3 h), repeated acute (3 exposures each of 3 h) and chronic (72 h) normobaric hyperoxic exposure in budgerigars (Melopsittacus undulatus) were evaluated by monitoring the effects on pulmonary enzymic antioxidants, and indicators of lipid peroxidation. All durations of oxygen exposure resulted in significant respiratory alkalosis and elevated pulmonary and blood glutathione peroxidase concentrations. The concentrations of other pulmonary enzymic antioxidants including glutathione reductase and superoxide dismutase were not significantly altered by oxygen exposure. Pulmonary concentrations of the lipid peroxidation markers malonaldehyde and 4-hydroxyalkenal were not significantly elevated following oxygen exposure. Plasma concentrations of 8-epi isoprostane F(2alpha) were significantly elevated following both acute and repeated acute exposure. The results indicate that in budgerigars, both acute and chronic oxygen exposure can result in significant alteration in respiratory function and increased production of reactive oxygen species.

Animals↗
PubMed2001

Normobaric hyperoxic stress in budgerigars: non-enzymic antioxidants.

The effects of oxygen exposure on pulmonary and blood non-enzymic antioxidant concentrations was evaluated in budgerigars (Melopsittacus undulatus). Budgerigars were exposed to acute (3 h), repeated acute (3 exposures each of 3 h) or chronic (72 h) normobaric hyperoxic environments and the pulmonary and plasma concentrations of selected non-enzymic antioxidants, namely glutathione, uric acid, alpha- and gamma-tocopherol and carotenoids were assayed. With increasing duration of oxygen exposure, the ratio of oxidised to reduced glutathione was significantly increased, while the concentrations of uric acid, alpha- and gamma-tocopherol and carotenoids were significantly reduced, especially following chronic oxygen exposure. Following acute and repeated acute exposure, alteration in glutathione concentrations and reduction in alpha-tocopherol concentrations indicated oxygen stress. Following chronic exposure, depletion of non-enzymic antioxidants indicated exhaustion of these protective mechanisms and progression from oxygen stress to oxygen toxicity.

Animals↗
PubMed2001

Pain management in the culture of critical care.

Pain of critically ill patients is undertreated. Undertreatment of pain may be related, in part, to the culture of critical care practice, where nurses are challenged to meet competing patient demands. Implementation of appropriate pain management strategies is within the critical care nurse's scope of practice and must be a priority when delivering patient care. Although the multidisciplinary team can make the best holistic pain management plan, nurses have extensive independence and latitude in administration of pharmacologic and nonpharmacologic interventions. It is, in fact, "primarily the nurses' responsibility to administer the proper drug and dose at the proper time". Fostering a culture within critical care units that promotes optimal pain management is influenced by unit leadership, the values held by the staff, nurse competency, and an effective quality program that includes process and outcome indicators of pain management.

Humans↗
PubMed2000

The proapoptotic BH3-only protein bim is expressed in hematopoietic, epithelial, neuronal, and germ cells.

Proapoptotic Bcl-2 family members activate cell death by neutralizing their anti-apoptotic relatives, which in turn maintain cell viability by regulating the activation of the cell death effectors, the caspases. Bim belongs to a distinct subgroup of proapoptotic proteins that only resemble other Bcl-2 family members within the short BH3 domain. Gene targeting experiments in mice have shown that Bim is essential for the execution of some but not all apoptotic stimuli, for hematopoietic cell homeostasis, and as a barrier against autoimmunity. There are three Bim isoforms, Bim(S), Bim(L), and Bim(EL), which have different proapoptotic potencies due at least in part to differences in interaction with the dynein motor complex. The expression pattern of Bim was investigated by immunohistochemical staining, immunoprecipitation followed by Western blotting, and in situ hybridization. Bim was found in hematopoietic, epithelial, neuronal, and germ cells. Bim(L) and Bim(EL) were coexpressed at similar levels in many cell types, but Bim(S) was not detected. Microscopic examination revealed a punctate pattern of Bim(L) and Bim(EL) immunostaining, indicating association with cytoplasmic structures. These results are discussed in the context of the phenotype of Bim-deficient mice and the post-translational regulation of Bim's pro-apoptotic activity.

3T3 Cells↗
PubMed2000

The role of bim, a proapoptotic BH3-only member of the Bcl-2 family in cell-death control.

Apoptosis is an evolutionarily conserved process for killing unwanted cells. Genetic and biochemical experiments have indicated that three groups of proteins are necessary for activation of the cell-death effector machinery: cysteine proteases, their adaptors, and proapoptotic Bcl-2 family members. Antiapoptotic Bcl-2 family members are needed for cell survival. We have cloned Bim, a proapoptotic Bcl-2 family member that shares with the family only a 9-16 aa region of homology [Bcl-3 homology region(BH3)], but is otherwise unique. Bim requires its BH3 region for binding to Bcl-2 and activation of apoptosis. Analysis of Bim-deficient mice has shown that Bim is essential for the execution of some but not all apoptotic stimuli that can be antagonized by Bcl-2. Bim-deficient mice have increased numbers of lymphocytes, plasma cells, and myeloid cells, and most develop fatal autoimmune glomerulonephritis. In healthy cells, Bim is bound to the microtubule-associated dynein motor complex, and is thereby sequestered from Bcl-2. Certain apoptotic signals unleash Bim and allow it to translocate to intracellular membranes, where it interacts with Bcl-2 or its homologues. These results indicate that BH3-only proteins are essential inducers of apoptosis that can be unleashed by certain death signals. Unleashed BH3-only proteins neutralize the prosurvival function of Bcl-2-like molecules, and this is thought to liberate Apaf-l-like adapters to activate caspase zymogens, which then initiate cell degradation.

Animals↗
PubMed1999

A patient-centered approach to advance medical planning in the nursing home.

OBJECTIVE: The objective of this study is to determine whether nursing home residents or their surrogates are willing and able to prioritize their goals for care and to demonstrate how these rankings can form the basis of a specific pattern of medical care. DESIGN: A prospective, descriptive study. SETTING: A 40-bed nursing unit for residents with mild to moderate impairments in a 725-bed teaching nursing home. RESULTS: Overall, 78% of patients or their families were willing to prioritize their goals, allowing the investigators to infer a pattern of care. The goals were interpreted as implying an intensive pattern in 21%, a comprehensive pattern in 16%, a basic pattern in 18%, palliation in 18%, and comfort only in 6% of residents. Goals chosen by residents who were able to select for themselves translated into more aggressive care than did the goals selected by surrogates. CONCLUSION: Goal-centered advance medical planning can be initiated in nursing homes by asking residents or their surrogates to prioritize their goals of care. These prioritizations can form the foundation for specific patterns of care.

Advance Care Planning↗
PubMed1998

The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3.

Paralogous regions are duplicated segments of chromosomal DNA that have been acquired during the evolution of the genome. Subsequent divergent evolution of the genes within paralogous regions can lead to the formation of gene families. Here, we report the identification of a region on Chromosome (Chr) 6 at 6p21.3 that is paralogous with the Spinal Muscular Atrophy (SMA) gene region on Chr 5 at 5q13.1. Partial characterization of this region identified nine sequences all of which are highly homologous to DNA sequences of the SMA gene region at 5q13.1. These sequences include four beta-glucuronidase sequences, two retrotransposon sequences, a novel cDNA, a Sequence Tagged Site (STS), and one that is homologous to exon 9 of the Neuronal Apoptosis Inhibitor Protein (NAIP) gene. The 6p21.3 paralogous SMA region may contain genes that are related to those in the SMA region at 5q13.1; however, a direct association of this region with SMA is unlikely given that no linkage of SMA with Chr 6 has been reported.

Base Sequence↗
PubMed1998

Rapid hybridoma screening method for the identification of monoclonal antibodies to low-abundance cytoplasmic proteins.

Screening assays are the most time-consuming and labor-intensive part of generating monoclonal antibodies (MAbs). Antibodies identified by enzyme-linked immunosorbent assay (ELISA) screening often are not suitable for their intended application such as immunofluorescence staining. We describe here a rapid and efficient flow cytometric screening procedure for the identification of MAbs directed against low-abundance cytoplasmic proteins, in our case, the pro-apoptotic molecule Bim. Cells from an equal mixture of a parental cell line and a subline expressing Bim were fixed, permeabilized and incubated with hybridoma supernatants. The supernatants were derived from a fusion of Sp2/0 plasmacytoma cells and spleen cells from a rat immunized with recombinant glutathione-S-transferase (GST)-BimL fusion protein. Secondary staining with fluorochrome-labeled anti-rat Ig antibodies allowed detection of clones expressing Bim-specific antibodies. The screening procedure was rapid and efficient, and most monoclonal antibodies identified were proven to be useful for immunofluorescence staining and other applications.

Animals↗
PubMed1998

Testing the Uniform Needs Assessment Instrument for hospital discharge planning with older adults.

The Uniform Needs Assessment Instrument (UNAI) was developed to systematically assess the continuing care needs of high-risk older adults in response to the 1986 Omnibus Budget Reconciliation Act. Based on previous studies, a revised UNAI was tested with 103 hospitalized older adults, comparing usual discharge planning with the UNAI. High interrater reliability was obtained. The UNAI had high (> or = 85%) sensitivity and specificity when comparing needs identification on the UNAI with subjects' reported needs at 10 to 14 days after discharge. Overall, the UNAI was more effective (sensitive and specific).

Aftercare↗
PubMed1998

Selective cyclooxygenase-2 inhibition by nimesulide in man.

Prostaglandins are generated through two isoforms of the enzyme cyclooxygenase, the constitutively expressed cyclooxygenase (Cox)-1 and Cox-2, which is induced at sites of inflammation. Selective inhibition of Cox-2 is desirable as this may avoid the gastropathy and platelet inhibition seen with nonselective agents. Moreover, these agents will allow us to examine the relative contribution of the two isoforms to prostaglandin formation in man. We examined the activity of nimesulide, a Cox-2 selective nonsteroidal antiinflammatory drug, in vitro against purified enzymes and in vivo in man. Nimesulide 100 mg twice daily or aspirin 300 mg three times daily were administered randomly for 14 days to 20 subjects complaining of musculoskeletal pain. Serum thromboxane B2 was determined as an index of Cox-1 activity and endotoxin-induced prostaglandin E2 formation in whole blood as an index of Cox-2 activity. Urinary excretion of prostaglandin metabolites was determined by GC/MS. Nimesulide was highly selective against ovine Cox-2, so that at concentrations attained in vivo, it had no effect on Cox-1 but completely suppressed Cox-2. Aspirin markedly inhibited serum thromboxane B2 (181.92 +/- 19.77 to 2.83 +/- 0.96 ng/ml, P <. 002), whereas nimesulide had very little effect (207.53 +/- 47.30 to 181.15 +/- 54.59 ng/ml). In contrast, nimesulide suppresses endotoxin-induced prostaglandin E2 formation (35.03 +/- 8.73 to 2.62 +/- 0.95 ng/ml, P =.002). As expected, aspirin reduced TX metabolite excretion, whereas nimesulide had no significant effect. In contrast, both compounds suppressed PGI2 formation to the same extent. The findings suggest that TX is largely Cox-1 derived. Moreover, Cox-2 is expressed in man and generates prostaglandin I2.

Cyclooxygenase 2↗
PubMed1996

Restructuring the clinical nurse specialist position to a unit-based role.

Role restructuring can be the key to maximizing efficiency, productivity, and operational effectiveness. The clinical nurse specialist role was restructured from a divisional project focus to a unit-based design to enhance the care of specific patient populations. The authors describe the process used to make this change, the outcomes achieved, and the lessons learned.

Efficiency, Organizational↗
PubMed1995

Development of the home care client satisfaction instrument.

Client (patient) satisfaction has been studied extensively in the health care sector, yet those receiving home health care services have been the focus of few studies. The purpose of this study was to test the reliability and validity of the Home Care Client Satisfaction Instrument (HCCSI). A total of 400 clients, randomly selected from 20 randomly chosen home care agencies in one state, completed the HCCSI and demographic form. Most respondents were older adults with multiple health problems and their families or informal support systems. Since data were skewed, item analysis was used. The revised instrument (HCCSI-R) is unidimensional and includes 12 items rated on a 5-point Likert scale measuring specific aspects of care. In addition, there are three global measures of satisfaction rated on a 10-point scale. All items except one had significant item-total correlations greater than .59. The total score correlates with likeliness to recommend the agency to others (.37, p = .0001), showing some evidence for criterion-related validity.

Aged↗
PubMed1992

Interventions related to circulatory care.

The validation of 21 circulatory nursing interventions has helped to articulate one component of critical care nursing. Circulatory nurses intervene in actual or potential physiologic problems and have distinct treatments to offer. The validation of these circulatory interventions will help in the building of a standardized language for nursing.

Cardiovascular Diseases↗