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Biomedical subjects

R Gallagher

Publications and source records attributed to R Gallagher.

At least 19 recordsLinked to original sources
PubMed2006

The effect of education and counselling on knowledge, attitudes and beliefs about responses to acute myocardial infarction symptoms.

The time that elapses from the onset of symptoms of acute myocardial infarction (AMI) to treatment has a significant effect on mortality and morbidity. This study reports the effectiveness of an education and counselling intervention on knowledge, attitudes and beliefs about AMI symptoms and the appropriate response to symptoms. The intervention was tested in a randomised controlled trial of 200 people with a history of coronary heart disease (CHD). The groups were equivalent at baseline on study outcomes, clinical history and sociodemographic characteristics with the exception of more women in the intervention group (38% vs. 24%). The results of repeated measures ANOVA showed that the intervention resulted in improved knowledge of CHD, AMI symptoms and the appropriate response to symptoms that was sustained to 12 months (p=0.02). There were no differences between groups' attitudes and beliefs over time. It is concluded that a short individual teaching and counselling intervention resulted in improved knowledge of CHD, AMI symptoms and the appropriate response to symptoms in people at risk of AMI sustained to 12 months.

Adaptation, Psychological↗
PubMed2006

Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK.

The neurofibromatosis type 2 NF2 gene product, merlin, is a tumor suppressor frequently inactivated in malignant mesothelioma (MM). To investigate a possible correlation between merlin inactivation and MM invasiveness, we restored merlin expression in NF2-deficient MM cells. Re-expression of merlin markedly inhibited cell motility, spreading and invasiveness, properties connected with the malignant phenotype of MM cells. To test directly whether merlin inactivation promotes invasion in a nonmalignant system, we used small interfering RNA to silence Nf2 in mouse embryonic fibroblasts (MEFs) and found that downregulation of merlin resulted in enhanced cell spreading and invasion. To delineate signaling events connected with this phenotype, we investigated the effect of merlin expression on focal adhesion kinase (FAK), a key component of cellular pathways affecting migration and invasion. Expression of merlin attenuated FAK phosphorylation at the critical phosphorylation site Tyr397 and disrupted the interaction of FAK with its binding partners Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase. In addition, NF2-null MM cells stably overexpressing FAK showed increased invasiveness, which decreased significantly when merlin expression was restored. Collectively, these findings suggest that merlin inactivation is a critical step in MM pathogenesis and is related, at least in part, with upregulation of FAK activity.

Animals↗
PubMed2004

A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes.

BACKGROUND: The availability of genotype-specific therapy for PML/RAR alpha(pos) acute promyelocytic leukemia (APL) requires that this disease be precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DR(low), CD34(low), P-glycoprotein(low) myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/RAR alpha fusion transcript. METHODS: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. RESULTS: In a test group of 58 APL patients, the most predictive immune profile was HLA-DR(low), CD11a(low) (alpha(L) subunit of the leukocyte integrin LFA-1), CD18(low) (beta(2) subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (alpha(M) leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). CONCLUSIONS: PML/RAR alpha(pos) APL cells typically lack leukocyte integrins. HLA-DR(low), CD11a(low), CD18(low) is a reliable surrogate antigen expression profile for PML/RAR alpha(pos) APL, irrespective of morphology and transcript isoform.

Antigens, Neoplasm↗
PubMed2004

A survey of cancer pain management knowledge and attitudes of British Columbian physicians.

INTRODUCTION: There are many potential barriers to adequate cancer pain management, including lack of physician education and prescription monitoring programs. The authors surveyed physicians about their specific knowledge of pain management and the effects of the regulation of opioids on their prescribing practices. METHODS: A questionnaire was mailed out to British Columbia physicians who were likely to encounter cancer patients. The survey asked for physicians' opinions about College of Physicians and Surgeons of British Columbia regulation and other issues related to their prescribing practices, and assessed basic knowledge of cancer pain management. RESULTS: There was a 69% return rate with a total of 4618 evaluable responses. There was a significant difference among medical disciplines, years in practice, number of chronic pain patients seen and size of community of practice. The highest knowledge scores were achieved by oncologists and the lowest scores were from surgeons. Those who practiced in smaller communities had a higher average knowledge score. Those who felt their knowledge about cancer pain was inadequate scored lower than those who felt their knowledge was adequate. The questions most frequently answered incorrectly (or by "don't know") were those about equianalgesic dosing (68%) and adequate breakthrough dosing (45%), revealing knowledge deficiencies that would significantly impair a physician's ability to manage cancer pain. CONCLUSIONS: The details of opioid prescribing are crucial areas to target education for cancer pain management. The surveyed physicians accepted the need for regulation of opioid prescribing with very few being fearful of scrutiny from the College of Physicians and Surgeons of British Columbia. However, the inconvenience of the triplicate prescription pad was more of a barrier to prescribing, it being of concern to 20% of respondents, particularly surgeons and medical specialists.

Analgesics, Opioid↗
PubMed2002

Controlling the physical behavior and biological performance of liposome formulations through use of surface grafted poly(ethylene glycol).

The presence of poly(ethylene glycol) (PEG) at the surface of a liposomal carrier has been clearly shown to extend the circulation lifetime of the vehicle. To this point, the extended circulation lifetime that the polymer affords has been attributed to the reduction or prevention of protein adsorption. However, there is little evidence that the presence of PEG at the surface of a vehicle actually reduces total serum protein binding. In this review we examine all aspects of PEG in order to gain a better understanding of how the polymer fulfills its biological role. The physical and chemical properties of the polymer are explored and compared to properties of other hydrophilic polymers. An evidence based assessment of several in vitro protein binding studies as well as in vivo pharmacokinetics studies involving PEG is included. The ability of PEG to prevent the self-aggregation of liposomes is considered as a possible means by which it extends circulation longevity. Also, a "dysopsonization" phenomenon where PEG actually promotes binding of certain proteins that then mask the vehicle is discussed.

Adsorption↗
PubMed2002

Effect of intestinal microflora on the urinary metabolic profile of rats: a (1)H-nuclear magnetic resonance spectroscopy study.

1. Analysis of urine by (1)H-nuclear magnetic resonance (NMR) spectroscopy is used to detect biochemical disturbances predictive of toxicological changes. Recent studies, using (1)H-NMR spectroscopy have suggested that Alderley Park rats can be classified as hippuric acid (HA) or m-(hydroxyphenyl)propionic acid (m-HPPA) excretors. Evidence exists for the role of intestinal microflora in the excretion of aromatic phenolic compounds including HA and m-HPPA. 2. We sought to investigate whether intestinal microflora contribute to the difference in excretion. Urinary HA and m-HPPA levels were monitored to characterize excretion over time. The effect of intestinal microflora on the (1)H-NMR spectrum was also investigated using antibiotics to sterilize the intestine. Finally, the levels of m-HPPA and phenylpropionic acid (a precursor for HA) were analysed in the caecum and colon (entire tissue, including contents). 3. Characterization confirmed the presence of HA and m-HPPA excretors; enquiries revealed that the rats were obtained from two floors within a barriered breeding unit. Housing the rats from the two floors together for 21 days resulted in comparable levels of HA and m-HPPA excretion demonstrating that the profiles are not stable. 4. Following antibiotic treatment, HA and m-HPPA excretion decreased, indicating that intestinal microflora contribute to the excretion of these compounds. Finally, m-HPPA levels were higher in the colon of rats that excreted m-HPPA whilst PPA was increased in the caecum and colon of rats that excreted HA. 5. These results demonstrate that the observed difference in HA/m-HPPA excretion is due to differences in the intestinal microflora.

Animals↗
PubMed2001

Lineage restriction of the RARalpha gene expression in myeloid differentiation.

To better understand the role of retinoids in myelopoiesis, expression of the retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors [RXRs]) were examined during differentiation of factor-dependent cell-Paterson (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast, expression of both RARalpha isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRalpha expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, these results suggest that erythropoiesis and granulopoiesis require diminished and enhanced RARalpha activities, respectively, which at physiological all-trans-retinoic acid (RA) concentrations may be accomplished by reciprocal effects of EPO and myelomonocytic growth factors on its expression. This hypothesis is corroborated by data showing that RA, which positively regulates RARalpha2 expression, can exert inhibitory effects on erythroid differentiation.

Bone Marrow↗
PubMed2001

The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N.

AQ4N is a bioreductive drug that can significantly enhance the anti-tumour effect of radiation and cyclophosphamide. The aim of this study was to examine the ability of AQ4N to potentiate the anti-tumour effect of cisplatin and to compare it to the chemopotentiation effect of tirapazamine. In the T50/80 murine tumour model, AQ4N (50-100 mg/kg) was administered 30 min, 2.5 or 6 h prior to cisplatin (4 mg/kg or 8 mg/kg); this produced an anti-tumour effect that was approximately 1.5 to 2 times greater than that achieved by a single 4 or 8 mg/kg dose of cisplatin. Tirapazamine (25 mg/kg) administered 2.5 h prior to cisplatin (4 mg/kg) resulted in a small increase in anti-tumour efficacy. AQ4N was also successful in enhancing the anti-tumour effect of cisplatin in the SCCVII and RIF-1 murine tumour models. This resulted in an increased cell kill of greater than 3 logs in both models; this was a greater cell kill than that observed for tirapazamine with cisplatin. Combination of cisplatin with AQ4N or tirapazamine resulted in no additional bone marrow toxicity compared to cisplatin administered alone. In conclusion, AQ4N has the potential to improve the clinical efficacy of cisplatin.

Animals↗
PubMed2001

Using a trade-show format to educate the public about death and survey public knowledge and needs about issues surrounding death and dying.

A public education event on death and dying, based on the design of a commercial trade show, was held to raise the profile of palliative care in the community. Attendees answered a questionnaire designed to assess their knowledge on issues about dying and their anticipated needs if they were to face a terminal illness. Healthcare providers knew significantly more about dying, but there were persistent misconceptions that morphine shortens life, causes addiction, and develops tolerance. The questionnaire revealed confusion about treatment choices available to patients and euthanasia. The anticipated needs questions revealed that increasing age leads to less concern about physical needs, and independence/control. Further public forums on death and dying will be held with attention to education on the identified issues and inclusion of wider education and cultural groups.

Adult↗
PubMed2001

Autologous fibrin sealant reduces pain after tonsillectomy.

OBJECTIVES/HYPOTHESIS: Pain is a major cause of morbidity after tonsillectomy. Although various efforts have been made to reduce pain, the use of oral analgesics, which can have adverse side effects, remains the standard of care. It is hypothesized that fibrin sealant, used to achieve hemostasis and enhance healing in many surgical procedures, might help decrease pain after this operation. STUDY DESIGN: A prospective, randomized, blinded study was performed on 20 children aged 5 to 17 years who were undergoing tonsillectomy, to evaluate the efficacy of FIBRIN SEALANT in reducing postoperative pain. METHODS: All patients pre-donated 40 mL of blood from which autologous concentrated fibrinogen was prepared by cryoprecipitation. In the fibrin sealant group, fibrinogen and topical bovine thrombin were sprayed onto the surgical site to form fibrin sealant at the conclusion of tonsillectomy. The 10 patients in the control group (C) received no fibrin sealant. Patients rated their level of pain immediately after surgery and at regular intervals for 3 days after surgery using the Wong-Baker Faces Pain Rating Scale (1-6). Emesis, postoperative bleeding, medications, and adverse events were also evaluated. RESULTS: At 7.00 P.M. on postoperative day (POD) 0, the mean +/- SD fibrin sealant group pain score (2.9+/-0.41 units) was significantly lower than for the C group (4.1+/-0.43 units; P < or = .05). There was also a trend in favor of less pain in the fibrin sealant group at 7:00 P.M. on POD 1, with a mean of 3.5+/-0.43 units versus 2.4+/-0.48 units for C (P = .15). The odds of a patient in C experiencing emesis were 8.16 times higher, (P < or = .05) than for patients in the fibrin sealant group. CONCLUSIONS: Fibrin sealant significantly reduced pain the evening after pediatric tonsillectomy and also decreased the chance of experiencing emesis. Thus fibrin sealant may be clinically useful as an adjunct to tonsillectomy.

Administration, Topical↗
PubMed2001

The diagnosis and neuropsychological assessment of adult attention deficit/hyperactivity disorder. Scientific study and practical guidelines.

The recognition of attention deficit/hyperactivity disorder (ADHD) in adults is a well documented, but relatively new development. Investigations of the disorder have indicated that disturbances in behavior and adjustment are common. These disturbances may be linked to poorly developed executive functions. This paper reviews the neuropsychological studies that have compared persons with ADHD to normal controls and to psychiatric controls. The review indicates that persons with ADHD share many neuropsychological characteristics with other persons with serious psychiatric conditions, although those with ADHD may have a particular profile of slowed performance in tasks of sustained attention and set shifting, and their use of working memory may be particularly impaired. The implications of research for clinical assessment are discussed. We contend that a neuropsychological orientation is necessary for making the diagnosis and gaining a full understanding of adult ADHD. A model for clinical assessment is proposed which utilizes a neuropsychological orientation and the targeted administration of neuropsychological instruments. The careful use of neuropsychological measures is warranted in providing an elaborate picture of a person's functioning, although the use of neuropsychological tests is not necessary to make the diagnosis.

Adult↗
PubMed2001

Nanomechanical properties of hydrated carious human dentin.

Most restorative materials are bonded to caries-affected dentin that has altered structure. We tested the hypothesis that hydrated dentin of the transparent zone did not have increased hardness or elastic modulus. Nanoindentation by modified AFM was used to determine site-specific elastic modulus and hardness for components of hydrated dentin from 8 carious and non-carious human teeth. Indentations in intertubular dentin were made at intervals from pulp through the affected layers (subtransparent, transparent, and discolored zones). The values of intertubular dentin increased slightly from near the pulp into the transparent zone, then remained constant or decreased slightly through transparent dentin (E, 18.3 GPa; H, 0.8 GPa; confirming the hypothesis), and decreased markedly through the discolored region. Peritubular dentin values were unaltered in transparent dentin, and intratubular mineral had values between those of normal peritubular and intertubular dentin. Superficial areas contained distorted tubules without peritubular dentin or intratubular mineral.

Analysis of Variance↗
PubMed2001

The effect of TGF-beta 2 on dentin apposition and hardness in transgenic mice.

Transforming growth factor beta, TGF-beta, is expressed during tooth formation and can induce pre-odontoblast differentiation and formation of functional odontoblast-like cells in vitro. In addition, exogenous TGF-beta can increase reparative dentin formation, presumably by acting on odontoblasts. In this study, we examined the tooth phenotype of transgenic mice, in which TGF-beta 2 expression is directed by the osteocalcin promoter. Previous studies have shown that these mice have a bone phenotype that resembles that of human osteoporosis, including the existence of spontaneous fractures. Microhardness testing of the enamel and dentin showed no differences in the molars of these transgenic mice as compared with those of their wild-type littermates. Consistent with the increase in bone mineral apposition rate previously reported in these mice, the dentin apposition rate appeared to be increased in the TGF-beta 2-overexpressing mice. Thus, in teeth, as in bone, TGF-beta 2 appears to stimulate the synthesis and deposition of matrix. Further studies are needed to understand the effect of TGF-beta 2 on distinct mineralized tissues (bone, dentin, and cementum) and to determine whether exogenous TGF-beta 2 may be useful for tooth repair.

Animals↗
PubMed2001

Consultation to administrators.

Mental health specialists can contribute to improvements in children's school experience when they work with administrators to incorporate up-to-date mental health knowledge into educational practice. Effective consultation is not simply a knowledge dissemination exercise. The impact of the consultant's input is determined by how responsive the consultation process is to the needs and assets of faculty, students, and the broader community.

Administrative Personnel↗
PubMed2000

Simultaneous PML/RARalpha and AML1/ETO expression with t(15;17) at onset and relapse with only t(8;21) in an acute promyelocytic leukemia patient.

We report a patient with acute promyelocytic leukemia with the common translocation (15;17) and PML-RARAalpha fusion gene. In relapse, blasts showed typical FAB M2 morphologic features, and the karyotype was 45,X, -Y,t(8;21). A reexamination of the leukemic cells at diagnosis revealed that an AML1-ETO fusion gene was also present at that time without cytogenetic evidence of t(8;21). In relapse, only t(8;21) was detected. Two different clones were identified by cytogenetic standard techniques. The association of two common translocations supervening in the same time in the same cells could not be established.

Adult↗