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Biomedical subjects

J D Roberts

Publications and source records attributed to J D Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2000

Problem-solving skills of senior student nurses: an exploratory study using simulation.

The Stages Model of problem-solving as evidenced in the use of the nursing process is the key vehicle for the operationalisation of problem-solving in current nursing practice. An expanded variant of the model formed the theoretical framework for this study which aimed to explore and compare the problem-solving skills of senior student nurses (n=253) from three pre-registration nurse education programmes (RGN, diploma RN, integrated degree). Students' care planning skills were explored using a video-tape simulation exercise and data were subjected to statistical testing. Findings indicated a large range in the global care plan scores and while performance was similar in a number of areas independent of programme type, certain key differences also emerged. The findings are discussed in the wider context of professional education and practice and the potential for further development of problem-solving skills in pre-registration nurse education is explored.

Education, Nursing↗
PubMed2000

Inhaled nitric oxide.

Nitric oxide (NO) is a free-radical gas that is an important signaling molecule in pulmonary vessels. Endogenous NO produced in endothelial cells from oxygen and L-arginine diffuses into smooth muscle cells in the vascular wall and causes vasodilatation. NO that diffuses into the blood vessel lumen is avidly bound by hemoglobin and does not cause important systemic vasodilatation. Inhaling low levels of NO rapidly and safely decreases pulmonary artery hypertension in many patients without causing systemic hypotension. In hypoxemic newborns with pulmonary hypertension, clinical studies indicate that inhaled NO increases systemic oxygen levels and decreases the requirement for extracorporeal membrane oxygenation. NO also has been observed to regulate cell proliferation. Recent studies suggest that inhaled NO selectively modulates the pulmonary artery proliferative response that is associated with lung injury. These later studies may indicate that inhaled NO can be applied to attenuate or prevent pulmonary artery disease in patients with injured lungs.

Administration, Inhalation↗
PubMed2000

Does multiple paternity improve fitness of the frog Crinia georgiana?

In the Australian myobatrachid frog Crinia georgiana simultaneous polyandry occurs in about half of all matings, which leads to multiple paternity, but reduced fertilization success and occasional female mortality. Multiple paternity may provide benefits to females that compensate for these costs, for example, through enhanced genetic diversity of a clutch. In nature, embryos and tadpoles of C. georgiana develop in shallow, temporary pools and may be exposed to fluctuating water levels and the risk of desiccation between rain events. Fertilization by genetically diverse sires may act as a bet hedge against these conditions. To evaluate this hypothesis, females were artificially mated with one or two males in the field and eggs and larvae reared in the laboratory under constant or fluctuating developmental conditions. Experiment 1 exposed embryos from single- and multiple-paternity clutches to conditions where eggs were completely covered during development or eggs sat in air on a moist substrate. Experiment 2 exposed freshly hatched larvae from single- and multiple-paternity clutches to constant wet conditions, where larvae were completely covered, or fluctuating wet conditions, where larvae ranged from being completely submersed to partially exposed over a 13-day cycle. We measured mean performance and best performance as alternate measures of genetic benefits. There were no effects of paternity on percent survival to hatching, time to hatching, body size at hatching, percent survival to metamorphosis, time to metamorphosis, or body size at metamorphosis. We also analyzed variance within clutches as a measure of genetic diversity. Again there were no predictable effects of multiple paternity. Polyandry does not appear to provide any genetic benefits that compensate for the high costs of polyandry in this species.

Animals↗
PubMed2000

A multicenter phase II trial of losoxantrone (DuP-941) in hormone-refractory metastatic prostate cancer.

Our purpose in this study was to determine the efficacy and toxicity of losoxantrone (DuP-941), an anthrapyrazole, in patients with metastatic hormone-refractory prostate cancer. Patients with metastatic prostate cancer progressing on androgen ablation therapy without demonstrable antiandrogen withdrawal response were treated with losoxantrone 50 mg/m2 i.v. bolus every 21 days. All of the patients had elevated serum prostate-specific antigen (PSA) before study entry and had no prior chemotherapy. Forty-three assessable patients were entered. The median age was 70.6 years (range, 53.9-85.9), median Karnofsky performance scale (KPS), 70% (50-90%), and the median serum PSA, 173 microg/liter (12.5-11,140). The median number of courses was 4 (1-9). Five patients (25%) had a partial response as defined by >50% decline in the serum PSA. Two of nine patients with measurable disease had partial responses and three had minor responses. Thirty percent of patients had improvement in KPS and 37% had an improvement in symptoms with decrease in pain and/or decrease in analgesic requirement. Nonhematological grade 3 and 4 toxicities were one each of grade 3 headache, grade 4 hypocalcemia, grade 3 hyperbilirubinemia, and grade 3 dyspnea. Twenty-six patients (60%) had grade 3 or 4 absolute neutropenia. In conclusion, losoxantrone demonstrated a partial biochemical response rate of 25%, response in measurable disease sites in 22%, and improvement in clinical symptoms in one-third of patients. In this study, PSA increase was not necessarily associated with lack of palliative response.

Aged↗
PubMed2000

Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034.

Glycinamide ribonucleotide formyltransferase (GARFT) is a component of the de novo purine synthesis pathway. AG2034 is a specific inhibitor of GARFT that was designed based on the GARFT crystal structure. In conjunction with Phase I studies at four clinical centers in the United States and United Kingdom, AG2034 pharmacology was evaluated in 54 patients receiving 1-11 mg/m2 AG2034 as a 2-5 min injection. Blood samples were obtained just prior to and 5, 15, 30, and 45 min, and 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, and 96 h after bolus injection during course 1. Limited sampling was also performed on course 3. Plasma AG2034 was measured using a sensitive and reproducible ELISA assay. AG2034 demonstrated a trimodal elimination pattern over 24 h, with median half-life (t(1/2))alpha = 8.7 min, t(1/2)beta = 72.6 min, and t(1/2)gamma = 364.2 min. AG2034 systemic clearance ranged from 9.4-144.5 ml/min/m2, and volume of distribution was 1.2-7.6 liters/m2. Course 1 AG2034 area under the concentration versus time curve (AUC) had a linear relationship with dose (r(s) = 0.86). Accumulation of AG2034 was evident, because course 3 AUC was higher than course 1 in 23 of 23 evaluable patients, but was not associated with an increase in erythrocyte AG2034. AG2034 systemic exposure had an impact on toxicity, because course 1 and course 3 AG2034 AUCs were significantly higher for patients with grade III/IV toxicity than patients with less than grade II toxicity (P < 0.001 and P = 0.001 for course 1 and course 3, respectively). This study demonstrates rapid systemic clearance of AG2034 and suggests pharmacokinetic approaches that may minimize patient toxicity and aid the development of this interesting class of anticancer agents.

Adult↗
PubMed1999

High-performance liquid chromatographic method for determination of vanillin and vanillic acid in human plasma, red blood cells and urine.

A simple high-performance liquid chromatographic method was developed for the determination of vanillin and its vanillic acid metabolite in human plasma, red blood cells and urine. The mobile phase consisted of aqueous acetic acid (1%, v/v)-acetonitrile (85:15, v/v), pH 2.9 and was used with an octadecylsilane analytical column and ultraviolet absorbance detection. The plasma method demonstrated linearity from 2 to 100 microg/ml and the urine method was linear from 2 to 40 microg/ml. The method had a detection limit of 1 microg/ml for vanillin and vanillic acid using 5 microl of prepared plasma, red blood cells or urine. The method was utilized in a study evaluating the pharmacokinetic and pharmacodynamic effects of vanillin in patients undergoing treatment for sickle cell anemia.

Benzaldehydes↗
PubMed1999

Comparison of cytotoxicity and cellular accumulation of polynuclear platinum complexes in L1210 murine leukemia cell lines.

The antitumor activity of the trinuclear Phase I clinical agent, BBR3464, is matched by that of polyamine-linked dinuclear complexes. The cytotoxicity and cellular accumulation of three polynuclear platinum complexes: [¿trans-PtCl(NH3)2¿2 mu-¿trans-Pt(NH3)2(H2N(CH2)6-NH2)2¿]4+ (BBR3464), [¿trans-PtCl(NH3)2¿2(H2N(CH2)3NH2(CH2)4NH2)]3+ (BBR3571), and [¿trans-PtCl(NH3)2¿2(H2N(CH2)6-NH2)]2+ (BBR3005), were studied in a series of murine L1210 cell lines and compared with cisplatin. Besides murine L1210 cell lines sensitive (/0) and resistant (/DDP) to cisplatin, the efficacy of the compounds in a cell line rendered resistant to BBR3464 (/3464) was examined. Finally, to examine possible uptake pathways of these novel charged complexes, cytotoxicity in a cell line resistant to the polyamine synthesis inhibitor, methylglyoxal-bis(guanylhydrazone) (/MGBG), was studied. Cytotoxicity profiles of BBR3571 most closely matched that of BBR3464. Both agents showed significantly reduced cytotoxicity in L1210/ BBR3464. The cytotoxicity of neither agent was affected by the polyamine uptake-deficient cell line and indeed both complexes showed significantly enhanced cytotoxicity in L1210/MGBG relative to wild-type L1210/0. The cellular uptake of both BBR3464 and BBR3571 was enhanced in L1210/DDP. These studies suggest that the chemical feature of a diamine linker containing an internal charge contributes significantly to the anticancer profiles of both the trinuclear platinum complex, BBR3464, which incorporates a charged platinum into a diamine linker, and the dinuclear platinum complex, BBR3571, which incorporates only a naturally occurring polyamine as diamine linker.

Animals↗
PubMed1999

Cellular pharmacology of polynuclear platinum anti-cancer agents.

Study of the cellular pharmacology of the dinuclear platinum complexes, BBR3005 ([¿trans-PtCl(NH3)2¿2H2N(CH2)6NH2]2+), BBR3171 ([¿cis-PtCl(NH3)2¿2H2N(CH2)6NH2]2+) and the trinuclear platinum complex, BBR3464 ([¿trans-PtCl(NH3)2¿2 mu-¿trans-Pt(NH3)2(H2N(CH2)6NH2)2¿]4+) was undertaken in wild type and cisplatin-resistant L1210 murine leukemia cell lines. All complexes are potent cytotoxic agents against the wild type cell line. Only BBR3464 shows enhanced activity against the cisplatin-resistant cell line following a brief exposure. This enhanced activity is attributable, in part, to preserved accumulation, which contrasts with diminished accumulation of cisplatin and both dinuclear platinum complexes. The cisplatin-resistant cell line is relatively tolerant of DNA adducts induced by both cisplatin and BBR3464, but BBR3464 is much less affected. All complexes induce DNA interstrand cross-links. Di/trinuclear complex-induced interstrand cross-linking peaks early, suggesting rapid genomic access and interaction. Subsequent decay suggests susceptibility to DNA repair mechanisms. Peak and area-under-the-curve values for interstrand cross-linking among the complexes correlate poorly with cytotoxic effects, especially in the cisplatin-resistant cell line. This suggests that all interstrand cross-linking adducts are not equal in their cytotoxic effect, or other, non-interstrand cross-linking adducts are significant. BBR3464 has been selected for clinical development largely on the basis of results from in vivo activity and toxicity studies. These results show BBR3464 to have unique properties in the context of acquired cisplatin-resistance that enhance its candidacy as a potential anticancer agent.

Animals↗
PubMed1999

Swainsonine protects both murine and human haematopoietic systems from chemotherapeutic toxicity.

The haematopoietic system is sensitive to cytotoxic damage and is often the site of dose-limiting toxicity. We previously reported that swainsonine, an inhibitor of protein glycosylation, reduced the bone marrow toxicity resulting from a single dose of anticancer drugs in otherwise healthy mice. However, more important questions are (1) can swainsonine protect tumour-bearing mice without interfering with the anti-tumour effects of the drugs, and (2) can swainsonine stimulate haematopoietic activity of human, as well as murine, bone marrow. We demonstrate here that swainsonine protects C57BL/6 mice bearing melanoma-derived tumours from cyclophosphamide-induced toxicity without interfering with the drug's ability to inhibit tumour growth. Similar results were obtained in vivo with 3'-azido-3'-deoxythymidine (AZT), a myelosuppressive agent often used in therapy for acquired immune deficiency syndrome. Swainsonine increased both total bone marrow cellularity and the number of circulating white blood cells in mice treated with doses of AZT that typically lead to severe myelosuppression. Swainsonine also increased the number of erythroid and myeloid colony forming cells (CFCs) in short-term cultures of murine bone marrow, restoring the number of progenitor cells to the control level in the presence of AZT doses that reduced CFCs by 80%. With respect to the sensitivity of human haematopoietic cells to swainsonine, we show that swainsonine protected human myeloid progenitor cells from AZT toxicity in vitro. These results suggest that swainsonine may be useful as an adjuvant in several types of human chemotherapy.

Adjuvants, Immunologic↗
PubMed1999

Shift work and its impact upon nurse performance: current knowledge and research issues.

Previous research investigating shift work and its impact upon the quality of registered nurse performance and outcomes (including biological, psychosocial and organizational) is reviewed. The present study, which involved non-participant observation of staff nurses (n = 34) within their first year of practice (Part 1 or Part 12 of the United Kingdom Professional Register), is described. The findings demonstrated support for earlier research which suggested that 12 1/2 hour shifts are associated with less effective performance. This study, together with previous research, highlights important indicators for the design and management of future empirical work which is required to investigate the influence of shift work upon process as well as outcomes for nurses, service users and the employing organization. This is particularly pertinent in the light of recent changes in work patterns. The well-being and effectiveness of the nursing workforce requires enhancement, and the effective management of shift-work is a key strategy in achieving this.

Employee Performance Appraisal↗
PubMed1998

Adenovirus-mediated gene transfer of cGMP-dependent protein kinase increases the sensitivity of cultured vascular smooth muscle cells to the antiproliferative and pro-apoptotic effects of nitric oxide/cGMP.

Studies in vitro have underestimated the importance of cGMP-dependent protein kinase (PKG) in the modulation of vascular smooth muscle cell (SMC) proliferation and apoptosis in vivo. This is attributable, in part, to a rapid decline in PKG levels as vascular SMC are passaged in culture. We used a recombinant adenovirus encoding PKG (Ad.PKG) to augment kinase activity in cultured rat pulmonary artery SMC (RPaSMC). Incubation of Ad. PKG-infected RPaSMC (multiplicity of infection = 200) with 8-Br-cGMP decreased serum-stimulated DNA synthesis by 85% and cell proliferation at day 5 by 74%. The effect of 8-Br-cGMP on DNA synthesis in Ad.PKG-infected RPaSMC was blocked by KT5823 (PKG inhibitor), but not by KT5720 (cAMP-dependent protein kinase inhibitor). A nitric oxide (NO) donor compound, S-nitrosoglutathione, at concentrations as low as 100 nM, inhibited DNA synthesis in Ad. PKG-infected RPaSMC, but not in uninfected cells or in cells infected with a control adenovirus. In addition, 8-Br-cGMP and S-nitrosoglutathione induced apoptosis in serum-deprived RPaSMC infected with Ad.PKG, but not in uninfected cells or in cells infected with a control adenovirus. These results demonstrate that modulation of PKG levels in vascular SMC can alter the sensitivity of these cells to NO and cGMP. Moreover, these observations suggest an important role for PKG in the regulation of vascular SMC proliferation and apoptosis by NO and cGMP.

Adenoviridae↗
PubMed1998

An exploratory study of similarities and differences between senior students from different pre-registration nurse education courses.

A triangulation design using two simulations, non-participant observation and a semi-structured interview to explore senior student nurse performance in South East England is described. A comparison of student nurse performance (registered general nurse [RGN] programme n = 34; registered nurse Project 2000 diploma programme n = 34; integrated degree programme n = 31) indicated many similarities but also some important differences in outcomes which included: a more systematic approach to information-seeking, better care-planning skills and higher quality nurse performance among integrated degree programme participants; use of a model and the immediate role of the nurse to guide information-seeking and better care-planning skills and weaknesses in clinical nurse performance among RGN programme participants; and weaknesses in the information-seeking, care-planning and clinical nurse performance among Project 2000 diploma participants. There were no significant differences between the clinical performance scores of the RGN and diploma programme participants. The interview data suggested that the integrated degree programme participants had a client focus in contrast to the professional focus of RGN and Project 2000 diploma participants. The findings, however, must be viewed within the context of an exploratory study of limited sample size. The research was funded by the English National Board for Nursing, Midwifery and Health Visiting.

Adult↗
PubMed1998

Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus.

It has been suggested that some glutamatergic synapses lack functional AMPA receptors. We used quantitative immunogold localization to determine the number and variability of synaptic AMPA receptors in the rat hippocampus. Three classes of synapses show distinct patterns of AMPA receptor content. Mossy fiber synapses on CA3 pyramidal spines and synapses on GABAergic interneurons are all immunopositive, have less variability, and contain 4 times as many AMPA receptors as synapses made by Schaffer collaterals on CA1 pyramidal spines and by commissural/ associational (C/A) terminals on CA3 pyramidal spines. Up to 17% of synapses in the latter two connections are immunonegative. After calibrating the immunosignal (1 gold = 2.3 functional receptors) at mossy synapses of a 17-day-old rat, we estimate that the AMPA receptor content of C/A synapses on CA3 pyramidal spines ranges from <3 to 140. A similar range is found in adult Schaffer collateral and C/A synapses.

Aging↗
PubMed1998

The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer.

Oligosaccharide moieties of cell-surface glycoproteins are thought to be involved in recognition events during cancer metastasis and invasion. Swainsonine, an inhibitor of the Golgi alpha-mannosidase II, has been shown to block pulmonary colonization by tumor cells and stimulate components of the immune system. Swainsonine also abrogates much of the toxicity of chemotherapeutic agents and stimulates bone marrow hematopoietic progenitor cells, suggesting additional therapeutic applications. We are currently characterizing the ability of swainsonine to modify cell growth in human and murine bone marrow progenitor cells. Furthermore, we are examining crucial steps in metastasis that depend upon cell surface molecules that play a role in cell-matrix interactions. Our work shows that tumor cell adhesion to collagen IV in vitro is rapidly stimulated by cis-polyunsaturated fatty acids and is dependent on protein kinase C activity. We are investigating the hypothesis that integrins are critical components of this adhesion and are examining potential signal transduction pathways that lead to the modulation of cell adhesion.

Animals↗
PubMed1997

Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.

BACKGROUND: Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension. METHODS: In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used. RESULTS: Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels. CONCLUSIONS: Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Administration, Inhalation↗
PubMed1997

Measuring clinical nurse performance: development of the King's Nurse Performance Scale.

The development of the King's Nurse Performance Scale to measure clinical nurse performance is described. Instrument construction was informed by the Slater Nursing Competencies Rating Scale [Wandelt, M. A. and Stewart, D. S. (1975) Slater Nursing Competencies Rating Scale. Appleton-Century Crofts, New York] together with key literature and the use of expert opinion. The instrument was utilised to observe the clinical performance of senior student nurses (n = 99) and data which were at the ordinal level were statistically analysed using a variety of non-parametric tests. Key findings of students' observed nursing practice are presented in a separate paper (While et al., unpublished document). Internal consistency testing of the King's Nurse Performance Scale using Cronbach's alpha coefficient revealed a promising alpha for the total instrument (r = 0.93). The subsection alphas indicated that further refinement may enhance the strength of the instrument as a tool for the measurement of performance in different domains of practice. The possible use of the Scale in the professional development of newly qualified nurses is suggested.

Clinical Competence↗
PubMed1997

Impaired vision for binocular tasks after unilateral optic nerve regeneration in the frog Litoria moorei.

Behavioural responses to objects in the binocular field were examined in frogs with one regenerate and one intact optic nerve. Data were compared to those for normal controls and for frogs with vision via one intact optic nerve. During prey acquisition, frogs with regenerated optic nerves underestimated the distance to the prey on their first strike; as a consequence, the regenerate series made several attempts to achieve a successful prey capture. By contrast, normal frogs and those using only one eye struck accurately at the prey and usually captured it on the first attempt. However, frogs using only one eye struck from a closer distance than either the regenerate or normal series. Frogs with regenerated optic nerves also made more errors than either of the other series when leaping through a set of closely spaced horizontally aligned rods. Our results show that prey capture and the negotiation of horizontally aligned rods is impaired in animals using one regenerated and one intact optic nerve as compared to both normal frogs and those using only one eye. We suggest that the poor visual performance for frogs with one regenerated and one intact optic nerve for tasks presented in the binocular field is related to the integration of a degraded and a normal image within the visual centres.

Animals↗