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Biomedical subjects

K Moran

Publications and source records attributed to K Moran.

At least 19 recordsLinked to original sources
PubMed2006

Parental perceptions of toddler water safety, swimming ability and swimming lessons.

The primary objective of the study was to examine parental perceptions on the role of toddler swimming ability and pre-school swimming lessons in drowning prevention. A self-administered questionnaire was used to obtain information on toddler water safety from parents (n = 882) whose 2 - 4-year-old toddlers were either attending early childhood centres (n = 327) or who were enrolled in swim schools (n = 555). Differences in attitudes between two groups of parents were measured by frequency, with Mann-Whitney U tests used to discern significant differences between groups. More swim school parents believed that: swimming was best taught at 2 years of age or less (42% vs. 29%); swimming lessons were the best way to prevent toddler drowning (57% vs. 47%); toddlers could learn to save themselves if they fell into water (43% vs. 33%); and that it was better to develop swimming ability rather than rely on adult supervision (35% vs. 30%). Many parents have an overly optimistic view of the role of swimming ability and pre-school swimming lessons in drowning prevention. This was especially so for parents with toddlers enrolled in lessons. Swim schools in particular need to counter parental misconceptions of the protective role of swimming and reiterate the importance of close adult supervision of toddlers around water.

Attitude↗
PubMed2004

Reduction of anti-Galalpha1,3Gal antibodies by infusion of types 2 and 6 gal trisaccharides conjugated to poly-L-lysine.

To investigate the specificity of anti-Galalpha1,3Gal (Gal) antibodies (Abs) with respect to Gal oligosaccharides of types 2 and 6, eight baboons received an intravenous infusion of either a poly-l-lysine conjugate of Gal type 2 (n = 5) or type 6 (n = 3), followed 48 h later by the alternative Gal type 6 or 2 conjugate, respectively. IgM Abs reactive to Gal type 2 were depleted by 80 to 89% by either Gal conjugate. IgM reactive to Gal type 6 was less efficiently depleted by the Gal type 2 conjugate (57% depletion) than the Gal type 6 (82% depletion). Gal-reactive IgG was depleted more slowly and less efficiently by either glycoconjugate (initially by only 28 to 54%). Our results indicate that the Gal type 6 conjugate depletes most anti-Gal IgM, but the Gal type 2 conjugate is less efficient in depleting anti-Gal IgM reactive with type 6. There remain small fractions of antibody that are unadsorbed, particularly of IgG, probably due to their low affinity and distribution in both the intra- and extra-vascular compartments.

Animals↗
PubMed2004

In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb).

Natural antibodies (Abs), predominantly anti-Gal alpha 1-3Gal (Gal) Abs, in non-human primates and human beings present a major hurdle to successful pig-to-primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naïve baboons using non-specific immunosuppressive or B cell-specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and total immunoglobulin (Ig)-secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme-linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments.

Animals↗
PubMed2004

Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation.

BACKGROUND: ABI793 (ABI) is a human monoclonal antibody (mAb) specific for human CD154. To assess the suitability of ABI for baboon transplantation studies, we carried out in vitro studies to determine ABI's reactivity with baboon cells expressing CD154, performed in vivo pharmacokinetic studies in two baboons, and tested the effect of ABI administration on elicited antibody production in two baboons undergoing either pig hematopoietic progenitor cell (PBPC) or heterotopic heart transplantation. METHODS: In vitro: Baboon peripheral blood mononuclear cells were activated in vitro to upregulate CD154, and binding of ABI to CD154 was measured by flow cytometry. In vivo: Serum levels of ABI were measured immediately before and 15 min after the intravenous administration of ABI (20 mg/kg) to two baboons over 28 days. Subsequently, ABI (25 mg/kg on days 0, 1, 4 and 7, and then 20 mg/kg every 5 days) was included in the immunosuppressive regimen in two pig-to-baboon transplants (PBPC or heart transplantation). RESULTS: In vitro: ABI was almost non-reactive to baboon T cells before stimulation, but bound to activated T cells. In vivo: In the pharmacokinetic study, trough levels of ABI (before the next dose) ranged between 190 and 580 microg/ml, and the estimated half-life was 10-15 days. There was no apparent toxicity. Following pig PBPC or heart transplantation, no elicited antibody was detected while ABI was being administered or during several weeks of follow-up. CONCLUSIONS: ABI functions in baboons, is well-tolerated, and prevents an elicited antibody response to pig antigens.

Animals↗
PubMed2004

Long bone fractures in children under 3 years of age: is abuse being missed in Emergency Department presentations?

OBJECTIVE: Distinguishing injuries due to accidents from those due to child abuse in young children is important to prevent further abuse. We aimed to study the presenting features, mechanism of injury, type of fracture and indicators of possible abuse in children under 3 years of age, presenting to the Emergency Department (ED) of a tertiary referral Children's Hospital, to see whether those injuries that were more likely abusive were distinguished from those that were more likely accidental. METHODS: We analysed the medical records from the Emergency Department Information System of all children below 3 years of age, who were treated for a long bone fracture at the Sydney Children's Hospital, Randwick, NSW, over a 1-year period. Demographic details, presenting complaint, mechanism of injury, type of fracture, other historical and examination data and action taken were noted. Nine indicators that raise suspicion of abuse were developed from the literature. Using these indicators, patients' ED notes were reviewed to establish whether long bone fractures suspicious for abuse had been referred for further evaluation. RESULTS: One hundred patients with a total of 103 fractures presented during the study period. No child had multiple fractures at a single visit. The fractures included 36 radius/ulna, 27 tibia/fibula, 20 humeral, 17 clavicular and three femoral. The mean age of patients was 21.6 months (range 13 days - 35 months). Fourteen patients were younger than 12 months. Review of the notes revealed 31 children with indicators suspicious for abuse, of whom 17 children had one indicator, 11 children had two indicators, and three children had three indicators. Only one child was referred for further evaluation to child protection. CONCLUSION: Abuse cannot usually be determined by fracture type alone. Doctors in the ED miss indicators for abuse because they do not look for these indicators in the history and examination. Knowledge of indicators that raise suspicion of abuse is needed for a further forensic assessment to occur. The development of specific referral guidelines, ongoing education and a comprehensive injury form may improve referral of children from the ED to child protection.

Child Abuse↗
PubMed2003

Shape relaxation of an elongated viscous drop.

The shape relaxation of a distorted viscous drop suspended in a quiescent immiscible liquid is analyzed in the creeping flow limit. The shape of the drop is axisymmetric, but otherwise arbitrary. The relaxation process is assumed to be driven by a constant interfacial tension and rate-limited by the Newtonian viscosities of the dispersed and continuous phases. For analysis, a least squares technique is developed which, compared to the more common boundary integral methods, is simpler to implement and especially suited for systems where one liquid is much more viscous than the other (i.e., when the viscosity ratio lambda, defined as the ratio of the dispersed to continuous phase viscosities, approaches either zero or infinity). To demonstrate the validity of the proposed least squares technique, its results are shown to agree well with boundary integral calculations for moderate values of lambda, and with experimental data when lambda is much larger than unity (approximately 10(6)). Predictions at infinite viscosity ratio--the regime in which the least squares technique is most useful--are then used to evaluate interfacial tensions associated with a system of practical importance, namely, the dispersion of heavy crude oil in an aqueous environment. This amounts to a novel and accurate technique for determining interfacial tensions--especially those of low values (1 mN/m or less)--between density-matched liquids where at least one of the phases is highly viscous. The experimental part of this study involves the use of suction pipettes to manipulate the shapes of individual micrometer-sized droplets, thus avoiding the need for complex flow-generating devices to create drop deformations.

Journal Article↗
PubMed2003

Shear-induced coalescence of emulsified oil drops.

Crude oil droplets, when suspended in water, possess negative surface charges which give rise to double-layer repulsive forces between the drops. According to conventional DLVO theory, the magnitude of this repulsion (based on the measured zeta potential) is more than sufficient to prevent coalescence of the droplets. Indeed, when two such droplets were brought together on direct (i.e., "head-on") approach, coalescence was rarely observed. Upon oblique approach, however, the same droplets were seen to coalesce readily. An oblique encounter must necessarily give rise to lateral relative motion-or shearing-between the droplet surfaces. It is speculated that, if the charge distributions at the droplet surfaces were heterogeneous, lateral shearing would facilitate many encounters between surface patches of different zeta potentials across the intervening water film. If the repulsion across any local region were sufficiently weak to allow formation of an oil bridge across the water film, coalescence of the drops would follow inevitably. With the hypothesis of surface heterogeneity, it is not necessary to invoke any additional colloidal interactions (such as "hydrophobic forces") to account for the observed droplet-droplet coalescence. This finding may have important implications for the underlying mechanisms of emulsion stability in general and the commercial extraction of bitumen from oil sands in particular.

Journal Article↗
PubMed2002

Pig hematopoietic cell chimerism in baboons conditioned with a nonmyeloablative regimen and CD154 blockade.

BACKGROUND: In an attempt to induce mixed hematopoietic chimerism and transplantation tolerance in the pig-to-primate model, we have infused high-dose porcine peripheral blood progenitor cells (PBPC) into baboons pretreated with a nonmyeloablative regimen and anti-CD154 monoclonal antibody (mAb). METHODS: Group 1 baboons (n=2) received a nonmyeloablative regimen including whole body irradiation, pharmacological immunosuppression, porcine hematopoietic growth factors, and immunoadsorption of anti-Galalpha1,3Gal (Gal) antibody before infusion of high doses of PBPC (2.7-4.6x10(10) cells/kg). In group 2 (n=5), cyclosporine was replaced by anti-CD154 mAb. Group 3 (n=3) received the group 1 regimen plus anti-CD154 mAb. RESULTS: In group 1, pig chimerism was detected in the blood by flow cytometry (FACS) for 5 days (with a maximum of 14%), and continuously up to 13 days by polymerase chain reaction (PCR). In group 2, pig chimerism was detectable for 5 days by FACS (maximum 33%) and continuously up to 28 days by PCR. In group 3, initial pig chimerism was detectable for 5 days by FACS (maximum 73%). Two of three baboons showed reappearance of pig cells on days 11 and 16, respectively. In one, in which no anti-Gal IgG could be detected for 30 days, pig cells were documented in the blood by FACS on days 16-22 (maximum 6% on day 19) and pig colony-forming cells were present in the blood on days 19-33, which we interpreted as evidence of engraftment. Microchimerism was continuous by PCR up to 33 days. CONCLUSIONS: These results suggest that there is no absolute barrier to pig hematopoietic cell engraftment in primates, and that this may be facilitated if the return of anti-Gal IgG can be prevented.

Animals↗
PubMed2001

Factors associated with pilot fatality in work-related aircraft crashes, Alaska, 1990-1999.

Work-related aircraft crashes are the leading cause of occupational fatality in Alaska, with civilian pilots having the highest fatality rate (410/100,000/year). To identify factors affecting survivability, the authors examined work-related aircraft crashes that occurred in Alaska in the 1990s (1990-1999), comparing crashes with pilot fatalities to crashes in which the pilot survived. Using data from National Transportation Safety Board reports, the authors carried out logistic regression analysis with the following variables: age, flight experience, use of a shoulder restraint, weather conditions (visual flight vs. instrument flight), light conditions (daylight vs. darkness), type of aircraft (airplane vs. helicopter), postcrash fire, crash location (airport vs. elsewhere), and state of residence. In the main-effects model, significant associations were found between fatality and postcrash fire (adjusted odds ratio (AOR) = 6.43, 95% confidence interval (CI): 2.38, 17.37), poor weather (AOR = 4.11, 95% CI: 2.15, 7.87), and non-Alaska resident status (AOR = 2.10, 95% CI: 1.05, 4.20). Protective effects were seen for shoulder restraint use (AOR = 0.40, 95% CI: 0.21, 0.77) and daylight versus darkness (AOR = 0.50, 95% CI: 0.25, 0.99). The finding that state of residence was associated with survivability offers new information on pilot survivability in work-related aircraft crashes in Alaska. These results may be useful in targeting safety interventions for pilots who fly occupationally in Alaska or in similar environments.

Accidents, Aviation↗
PubMed2000

An assessment of the value of intraperitoneal meperidine for analgesia postlaparoscopic tubal ligation.

UNLABELLED: Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P: < 0.01) and with movement (P: < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation. IMPLICATIONS: The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.

Adult↗
PubMed2000

Thermally induced shrinkage of joint capsule.

Thermal shrinkage of collagen currently is being used in orthopaedic surgery to treat ligamentous laxity. Understanding the kinetics of collagen shrinkage is key to revealing the events that take place during application of thermal energy. To elucidate the thermokinetic properties of collagen, punch biopsies of bovine joint capsule were immersed in a heated saline bath at temperatures between 20 degrees and 90 degrees C for periods up to 60 minutes. The resulting tissue thermal shrinkage was measured by the change in the cross-sectional area of the specimens. Only a small amount of shrinkage occurred at temperatures below 63 degrees C, and increasing amounts and rates of shrinkage were seen at temperatures between 63 degrees and 72 degrees C. The denaturation kinetics of bovine knee collagen, which could be described by a first order reaction rate, had an activation energy of 2.3 x 10(5) kJ/mol.

Animals↗
PubMed1999

Distress, personality, and mammography utilization among women with a family history of breast cancer.

The authors examined the impact of psychological distress and the personality construct of conscientiousness (as measured by the Neuroticism, Extraversion, and Openness-Five Factor Inventory) on mammography utilization among women who were at increased risk for breast cancer. Participants were 200 women who had at least 1 first degree relative with breast cancer. Overall, 80% of the participants had obtained a mammogram in the previous year. Analyses controlling for potential confounders (perceived risk, decisional balance, and physician recommendation for mammography), revealed that distress was negatively associated with mammography utilization among participants who were low in conscientiousness. Distress was not significantly related to mammography utilization among highly conscientious women. The results are discussed in terms of their implications regarding interventions designed to increase mammography utilization in this population.

Adult↗
PubMed1997

High-level expression of the prohormones proenkephalin, pro-neuropeptide Y, proopiomelanocortin, and beta-protachykinin for in vitro prohormone processing.

Prohormone substrates are required for investigation of the proteolytic processing of prohormones and proproteins into active peptide hormones and neurotransmitters. However, the lack of prohormone proteins has been a limiting factor in elucidating proteolytic mechanisms for conversion of prohormones into active peptides. Therefore, in this study, cloned cDNAs encoding the prohormones proenkephalin (PE), pro-neuropeptide Y (pro-NPY), pro-opiomelanocortin (POMC), and beta-protachykinin (beta-PT) were utilized to express recombinant prohormones in Escherichia coli. High-level expression of milligrams of prohormones was achieved with the pET3c expression vector utilizing the T7 promoter for production of PE, pro-NPY, and POMC, as demonstrated by SDS-PAGE gel electrophoresis, Western blots, and 35S-methionine labeling. In addition, beta-PT was expressed at high levels as fusion proteins with the maltose-binding protein and glutathione S-transferase by the pMAL-c and pGEX-2T expression vectors, respectively. Relative rates of processing by the established processing proteases "prohormone thiol protease" (PTP), 70-kDa aspartyl protease, and PC1/ 3 and PC2 (PC, prohormone convertase) were examined with purified PE, pro-NPY, and POMC. Distinct preferences of processing enzymes for different prohormones was demonstrated. PTP preferred PE and pro-NPY substrates, whereas little processing of POMC was detected. In contrast, the 70-kDa aspartyl protease cleaved POMC more readily than pro-NPY or PE. However, PC1/3 and PC2 prefer POMC as substrate. Demonstration of selectivity of processing enzymes for prohormone substrates illustrates the importance of expressing recombinant prohormones for in vitro processing studies.

Animals↗
PubMed1996

The online patient meeting.

Studies have shown the importance of social support for health, and the value of patient support groups. Today we are seeing a further development of the idea of the patient meeting: online discussions on the internet and other computer networks. This paper reports on the online activities of patients with amyotrophic lateral sclerosis. The paper explores key questions in the evaluation of online patient meetings, such as the ability of patients to discuss their problems frankly, the availability and accuracy of advice, the spread and control of rumours.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Biological diversity, indigenous knowledge, drug discovery and intellectual property rights: creating reciprocity and maintaining relationships.

When new plant-derived therapeutics based on indigenous knowledge are being explored, it is important that the pharmaceutical companies return benefits to the native populations and the local governments from which the research material was obtained. When a potentially marketable plant product is being developed, it is essential that equitable agreements have already been established between the pharmaceutical companies and the people and/or countries from which this indigenous knowledge was acquired. Equally important is the commitment to provide immediate reciprocity that will enhance the welfare, the biocultural diversity and the well-being of the forest peoples. These measures should commence when a research project begins and continue during its duration. The development of these measures must be based upon the expressed needs of the indigenous communities. The relationship between the stability of the rain forest biocultural diversity, the creation and development of agro-forest resources and the long term benefits to the forest people is highlighted. Examples of initiatives taken by Shaman Pharmaceuticals Inc. and the Healing Forest Conservancy are described and discussed in the context of exploring appropriate use of intellectual property law to address the ethical issues facing all business and research groups working in the tropics.

Awards and Prizes↗
PubMed1995

"Prohormone thiol protease" (PTP) processing of recombinant proenkephalin.

The "prohormone thiol protease" (PTP) from adrenal medullary chromaffin granules has been demonstrated as a novel cysteine protease that converts the model enkephalin precursor, ([35S]Met)-preproenkephalin, to appropriate enkephalin related peptide products [Krieger, T. J., & Hook, V. Y. H. (1991) J. Biol. Chem. 266, 8376-8383; Kreiger, T. J., Mende-Mueller, L., & Hook, V. Y. H. (1992) J. Neurochem. 59, 26-31; Azaryan, A. V., & Hook, V. Y. H. (1994) FEBS Lett. 341, 197-202]. In this report, PTP processing of authentic proenkephalin (PE) was examined with respect to production of appropriate intermediate products, and kinetics of PE processing were assessed. Recombinant PE was obtained by high level expression in Escherichia coli, with the pET3c expression vector; PE was then purified from E. coli by DEAE-Sepharose chromatography, preparative gel electrophoresis, and reverse-phase HPLC. Authentic purified PE was confirmed by amino acid composition analyses and peptide microsequencing. In time course studies, PTP converted PE (12 microM) to intermediates of 22.5, 21.7, 12.5, and 11.0 kDa that represented NH2-terminal fragments of PE, as assessed by peptide microsequencing. Differences in molecular masses of the 22.5, 21.7, 12.5, and 11.0 kDa products reflect PTP processing of PE within the COOH-terminal region of PE, which resembles PE processing in vivo [Liston, D. L., Patey, G., Rossier, J., Verbanck, P., & Vanderhaeghen, J. (1983) Science 225, 734-737; Udenfriend, S., & Kilpatrick, D. L. (1983) Arch. Biochem. Biophys. 221, 309-314]. Products of 12.5, 11.0, and 8.5 kDa were generated by PTP cleavage between Lys-Arg at the COOH-terminus of (Met)enkephalin-Arg6-Gly7-Leu8.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Pulsed Ho:YAG laser meniscectomy: effect of pulsewidth on tissue penetration rate and lateral thermal damage.

BACKGROUND AND OBJECTIVE: Studies need to define the optimal parameters under which the holmium laser should operate for arthroscopic meniscectomy. This study was designed to analyze the effect of various Holmium wavelength pulsewidths on human meniscal tissue penetration rates and lateral thermal injury. STUDY DESIGN/MATERIALS AND METHODS: Using a pulsed Holmium: YAG laser at a wavelength of 2.1 microns, the effect of various pulse-widths on tissue penetration rates as well as the degree of accompanying thermal damage in human meniscal tissue was evaluated in a specially designed jig. Holding the energy constant at 500 mJ per pulse, the pulsewidth was varied between 100 and 600 microseconds. RESULTS: Fiber penetration of meniscal tissue was found to be fastest at a pulsewidth of 250 microseconds. As the pulsewidth was increased or decreased around this number, the observed penetration time decreased, although no statistical difference was found. The size of the hole created was inversely related to the penetration time. Microscopic examination revealed zones of lateral thermal effect extending 800 microns from the ablation site. CONCLUSION: No relationship between the pulsewidth and the lateral thermal effect could be found.

Adult↗