Biomedical subjects

J Graham

Publications and source records attributed to J Graham.

At least 91 records · Page 5Linked to original sources

PubMed2000

Qualitative analysis of the clinician interview-based impression of change (Plus): methodological issues and implications for clinical research.

The Clinician Interview-Based Impression of Change, plus carer interview (CIBIC-Plus), is widely used in antidementia drug trials. It comprises Likert scales for disease severity and changes, and written accounts summarizing semistructured interviews evaluating behavior, cognition, and function. Studies using the CIBIC-Plus have focused on the numeric scores to the exclusion of the textual data. Our study explored both sets of data to evaluate whether the CIBIC-Plus written data supported (a) the clinicians' global evaluation of patients' changes during treatment, and (b) the emergence of consistent treatment effects. The global (numeric) scales of change were inconsistently supported by the textual data provided in the CIBIC-Plus. No consistent treatment effects were noted. Methodological problems presently limit the retrospective use of the CIBIC-Plus textual data. Improved standardization of note-taking in the CIBIC-Plus textual data may allow for a better understanding of the typical profiles and clinical importance of changes seen in the course of dementia treatment.

Aged↗

PubMed2000

Effect of inhibition of cyclooxygenase on pre- and postjunctional actions of peroxides in the iris-ciliary body.

In the present study, we investigated the effect of inhibition of cyclooxygenase (COX) with flurbiprofen (FBF) on peroxide-induced enhancement of field-stimulated [3H]norepinephrine ([3H]NE) release from bovine isolated irides. Furthermore, the effect of FBF was examined on peroxide-induced attenuation of contractions evoked by carbachol on this tissue. Irides were prepared for studies of neurotransmitter release and for measurement of contractile tension in vitro. Pretreatment of tissues with FBF (10 microM) caused significant (P < 0.001) rightward shifts of concentration-response curves to H2O2 and also decreased cumene hydroperoxide (cuOOH)-induced enhancement of evoked [3H]NE release. FBF (10 microM) partially prevented the attenuation of carbachol-induced contractions induced by H2O2 (300 microM) and cuOOH (300 microM). We conclude that inhibition of the biosynthesis of prostanoids reduced both the prejunctional stimulatory effects of H2O2 and cuOOH on sympathetic neurotransmission and inhibitory effects of peroxides on carbachol-induced contractions the in the bovine isolated iris.

Animals↗

PubMed2000

Job stress and satisfaction among clinical radiologists.

AIMS: Consultant radiologists appear to be at greater risk of burnout than consultants working in other specialties. The aim of this study was to examine sources of stress and satisfaction at work for radiologists and hospital consultants in other specialties in order to try to understand this difference. MATERIALS AND METHODS: A postal questionnaire survey of psychiatric morbidity (12-item General Health Questionnaire), burnout (Maslach Burnout Inventory) and sources of job stress and satisfaction (study-specific questionnaires) was carried out among a random sample of 882 hospital consultants working in radiology and three other specialties (surgery, gastroenterology and oncology). RESULTS: The most stressful aspect of work for radiologists was work overload. Inadequacies in current staffing and facilities and concerns about funding were also major sources of stress, as were impositions made on radiologists by other clinicians. The most important sources of satisfaction for radiologists were their relationships with patients and being perceived to do their job well by colleagues. Importantly, radiologists reported less satisfaction than the other specialists from many of the aspects of work measured. A greater proportion of radiologists than other specialists felt insufficiently trained in communication skills [80% (n = 168) vs 47% (n = 310);P < 0.001] and management skills [84% (n = 179) vs 76% (n = 506);P < 0.05]. CONCLUSION: These data highlight aspects of radiologists' work which need to be tackled in order to reduce their stress and increase their satisfaction, and thereby their risk of burnout.

Burnout, Professional↗

PubMed2000

Fracture and fatigue properties of acrylic bone cement: the effects of mixing method, sterilization treatment, and molecular weight.

The purpose of this study was to characterize the relative and combined effects of sterilization, molecular weight, and mixing method on the fracture and fatigue performance of acrylic bone cement. Palacos R brand bone cement powder was sterilized using ethylene oxide gas (EtO) or gamma irradiation. Nonsterile material was used as a control. Molecular weights of the bone-cement powders and cured cements were measured using gel permeation chromatography. Hand and vacuum mixing were employed to mold single edge-notched bend specimens for fracture toughness testing. Molded dog-bone specimens were used for fatigue tests. Electron microscopy was used to study fracture mechanisms. Analysis of variance and Student t-tests were used to compare fracture and fatigue performance between sterilization and mixing groups. Our results indicate that vacuum mixing improved significantly the fracture and fatigue resistance (P<.05, P<.07) over hand mixing in radiation-sterilized and EtO-sterilized groups. In vacuum-mixed cement, the degradation in molecular weight resulting from gamma irradiation decreased fracture resistance significantly when compared with EtO sterilization and control (P<.05). A corresponding decrease in fatigue resistance was observed in the cement that was degraded severely by a radiation dose of 10 MRad (P<.05). In contrast, EtO sterilization did not result in a significantly different fracture resistance when compared with unsterilized controls for vacuum-mixed cement (P>.1). For hand-mixed cement, fracture and fatigue resistance appeared to be independent of sterilization method. This independence is believed to be the result of higher porosity that compromised the mechanical properties and obscures any effect of sterilization. Our results indicate that a combination of nonionizing sterilization and vacuum mixing resulted in the best mechanical performance and is most likely to contribute to enhanced longevity in vivo.

Animals↗

PubMed2000

Improving the outcome of salvage treatment for non-seminomatous germ cell tumours (NSGCT).

Between 1991-96, 41 patients were treated in this unit for relapsed non-seminomatous germ cell tumours (NSGCT). Twenty-eight patients had raised markers at relapse: 17 required salvage chemotherapy and post-chemotherapy surgery, 11 only chemotherapy. In addition 9 patients received high dose chemotherapy. Overall 16/28 patients (57%) requiring chemotherapy remain alive, 14 (50%) disease free. Of the 17 patients treated with chemotherapy and surgery: 12 remain alive, 10 (59%) with no evaluable disease. Only 4/11 (36%) patients treated with chemotherapy alone remain alive, all in complete remission (CR). For relapse with raised markers, univariate analysis suggests that less than CR to induction therapy, resulting in the presence of residual disease is the most important predictor of poor outcome (P<0.001). All of the 13 patients relapsing with normal markers remain alive, having been primarily treated surgically. Overall these results indicate an improving outlook for relapsed NSGCT.

Adult↗

PubMed2000

Two genes required for meiotic recombination in Drosophila are expressed from a dicistronic message.

We have isolated two alleles of a previously unidentified meiotic recombination gene, mei-217. Genetic analysis of these mutants shows that mei-217 is a typical "precondition" gene. The phenotypes of the mutants are meiosis specific. The strongest allele has <10% of the normal level of crossing over, and the residual events are distributed abnormally. We have used double mutant analysis to position mei-217 in the meiotic recombination pathway. In general, mutations causing defects in the initiation of meiotic recombination are epistatic to mutations in mei-41 and spnB. These two mutations, however, are epistatic to mei-217, suggesting that recombination is initiated normally in mei-217 mutants. It is likely that mei-217 mutants are able to make Holliday junction intermediates but are defective in the production of crossovers. These phenotypes are most similar to mutants of the mei-218 gene. This is striking because mei-217 and mei-218 are part of the same transcription unit and are most likely produced from a dicistronic message.

Amino Acid Sequence↗

PubMed2000

Conditional genotypic probabilities for microsatellite loci.

Modern forensic DNA profiles are constructed using microsatellites, short tandem repeats of 2-5 bases. In the absence of genetic data on a crime-specific subpopulation, one tool for evaluating profile evidence is the match probability. The match probability is the conditional probability that a random person would have the profile of interest given that the suspect has it and that these people are different members of the same subpopulation. One issue in evaluating the match probability is population differentiation, which can induce coancestry among subpopulation members. Forensic assessments that ignore coancestry typically overstate the strength of evidence against the suspect. Theory has been developed to account for coancestry; assumptions include a steady-state population and a mutation model in which the allelic state after a mutation event is independent of the prior state. Under these assumptions, the joint allelic probabilities within a subpopulation may be approximated by the moments of a Dirichlet distribution. We investigate the adequacy of this approximation for profiled loci that mutate according to a generalized stepwise model. Simulations suggest that the Dirichlet theory can still overstate the evidence against a suspect with a common microsatellite genotype. However, Dirichlet-based estimators were less biased than the product-rule estimator, which ignores coancestry.

Alleles↗

PubMed2000

A coalescent model of ancestry for a rare allele.

In disequilibrium mapping from data on a rare allele, interest may focus on the ancestry of a random sample of current descendants of a mutation. The mutation is assumed to have been introduced into the population as a single copy a known time ago and to have reached a given copy number within the population. Theory has been developed to describe the ancestral distribution under arbitrary patterns of population expansion. Further results permit convenient realization of the ancestry for a random sample of copies of a rare allele within populations of constant size or within populations growing or shrinking at constant exponential rate. In this article, we present an efficient approximate method for realizing coalescence times under more general patterns of population growth. We also apply diagnostics, checking the age of the mutation. In the course of the derivation, some additional insight is gained into the dynamics of the descendants of the mutation.

Alleles↗

PubMed2000

Collaborative research: a community approach.

Collaborative nursing research is an effective means to increase research productivity. The essentials of collaborative research are contribution, communication, commitment, consensus, compatibility, and a cohesive approach toward a positive outcome. The purpose of the demonstration project was to describe a collaborative process in one community, culminating in a research utilization study and development of nursing standards pertaining to an aggregate population of patients.

Clinical Nursing Research↗

PubMed2000

Change in primary health care: new wine in old bottles?

Describes the findings from the first year of an evaluation of change at a PMS+ site in West Cumbria. The study has used qualitative methods including non-participant observation at the site; face to face interviews with 28 clinical staff; group interviews with administrative and secretarial staff; and the collection of documents. Analysis of the data against a set of "outcome indicators" shows that significant progress has been made towards implementing the model of primary care delivery described in the pilot proposal. Multidisciplinary working is developing in the clinical action groups and the establishment of a primary care emergency unit has changed general practitioner workloads. The new organisation structure is not yet working wholly as anticipated but recently initiated changes are intended to strengthen the role and authority of the management board.

Data Collection↗

PubMed2000

Detection of occult thymoma during exercise thallium 201, technetium 99m tetrofosmin imaging for coronary artery disease.

Thallium (Tl) 201 and technetium (Tc) 99m tetrofosmin single-photon emission CT are routinely used in the evaluation of coronary artery disease. Mediastinal tumors demonstrate Tl 201 and Tc 99m tetrofosmin uptake. We report a 56-year-old man who developed chest pain after a previously successful angioplasty and stent of the left anterior descending coronary artery. He underwent a Tl 201, Tc 99m tetrofosmin exercise study. Abnormal mediastinal activity was visualized in both the Tl 201 and Tc 99m tetrofosmin images. Subsequently, the patient underwent resection of a stage II thymoma. Unanticipated focal extracardiac accumulation during myocardial scintiscanning should lead to further investigation to exclude mediastinal tumor.

Coronary Disease↗

PubMed2000

The length of the CTLA-4 microsatellite (AT)N-repeat affects the risk for type 1 diabetes. Diabetes Incidence in Sweden Study Group.

CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)n microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping fo determine the length of the 3'-end (AT)n repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3'-end (AT)n repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes.

Abatacept↗

PubMed2000

Collecting cancer risk factor data from hospital outpatients: use of touch-screen computers.

The aim of this study was to assess the prevalence of selected cancer risk factor data from hospital outpatients and the proportion of "at risk" patients who would like help from hospital staff to reduce risk factors. A touch-screen computer collected data from outpatients in Newcastle, NSW, Australia. Eight hundred and nineteen outpatients completed the computerized interview. Of these, 35% were smokers, of whom 25% said that they would like help to stop smoking; 47% were overweight, with 48% indicating that they wanted assistance; 17% consumed harmful levels of alcohol, with 2% wanting help; 30% of eligible women were overdue for a Pap test, of whom 75% said that they wanted a referral to be screened, and 25% were overdue for a mammogram, of whom 83% said that they would like a referral for an examination. Touch-screen computerized health risk assessments are practical for collecting and monitoring valid cancer risk factor data for hospital outpatients.

Adolescent↗

PubMed1999

Determination of betulinic acid in mouse blood, tumor and tissue homogenates by liquid chromatography-electrospray mass spectrometry.

A rapid and sensitive high-performance liquid chromatography-electrospray MS method has been developed to determine tissue distribution of betulinic acid in mice. The method involved deproteinization of these samples with 2.5 volumes (v/w) of acetonitrile-ethanol (1:1) and then 5 microl aliquots of the supernatant were injected onto a C18 reversed-phase column coupled with an electrospray MS system. The mobile phase employed isocratic elution with 80% acetonitrile for 10 min; the flow-rate was 0.7 ml/min. The column effluent was analyzed by selected ion monitoring for the negative pseudo-molecular ion of betulinic acid [M-H]- at m/z 455. The limit of detection for betulinic acid in biological samples by this method was approximately 1.4 pg and the coefficients of variation of the assay (intra- and inter-day) were generally low (below 9.1%). When athymic mice bearing human melanoma were treated with betulinic acid (500 mg/kg, i.p.), distribution was as follows: tumor, 452.2 +/- 261.2 microg/g; liver, 233.9 +/- 80.3 microg/g; lung, 74.8 +/- 63.7 microg/g; kidney, 95.8 +/- 122.8 microg/g; blood, 1.8 +/- 0.5 microg/ml. No interference was noted due to endogenous substances. These methods of analysis should be of value in future studies related to the development and characterization of betulinic acid.

Animals↗

PubMed1999

Peripheral neuropathy in a turkey vulture with lead toxicosis.

Clinical, electromyographic, and pathologic findings characteristic of lead toxicosis were detected in a turkey vulture (Cathartes aura). The bird had generalized lower motor neuron dysfunction that progressed over 5 days. Electromyography revealed diffuse denervation potentials and a presumed decrement in the sciatic-tibial nerve conduction velocity. Histologic examination of peripheral nerves obtained at necropsy revealed changes that could be compatible with lead-induced neuropathy. Lead toxicosis was confirmed by determination of blood lead concentrations. Lead toxicosis causing neurologic disorders in birds has been described. However, this report emphasizes the effects of lead on the peripheral nervous system and demonstrates the use of electromyography for diagnosis of peripheral neuropathy in birds.

Animals↗

PubMed1999

Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice.

Betulinic acid is a naturally occurring pentacyclic triterpenoid. Betulinic acid has recently been selected by the National Cancer Institute for addition into the RAID (Rapid Access to Intervention in Development) programme. The agent exhibits potential anti-tumour activity and functions in this regard via apoptosis. The objective of the present study was to determine the pharmacokinetics of betulinic acid in CD-1 mice. Serum samples were obtained at designed times after a single 250 or 500 mg/kg intraperitoneal (IP) dose of betulinic acid. Tissue samples (skin, heart, liver, spleen, kidney, lung, brain, colon, caecum, ovary, uterus, thymus, lymph node, bladder, perirenal fat, mammary gland and small intestine) were collected after betulinic acid administration (500 mg/kg). Betulinic acid was extracted with methylene chloride and quantitatively analysed by HPLC/MS. Oleanolic acid and madecassic acid were used as internal standards. Pharmacokinetic parameters were calculated using the WinNonlin pharmacokinetic software package. A two-compartment, first-order model was selected for pharmacokinetic modelling. The results showed that after IP 250 and 500 mg/kg betulinic acid, the serum concentrations reached peaks at 0.15 and 0.23 h, respectively. The 250 and 500 mg/kg above betulinic acid IP doses were found to have elimination half-lives of 11.5 and 11.8 h and total clearances of 13.6 and 13.5 L/kg/h, respectively. The pharmacokinetic parameters observed for IP betulinic acid 500 mg/kg in the skin of mice were as follows: k(a) (h(-1)) 0.257, k(10) (h(-1)) 0.234, t(1/2(alpha)) (h) 2.63, t(1/2(beta)) (h) 20.2, V (L/kg) 0.61, AUC (microg/h/mL) 3504, T(max) (h) 3.90 and C(max) (microg/mL) 300.9. The distribution of betulinic acid in tissues at 24 h post-IP administration in a descending order was as follows: perirenal fat, ovary, spleen, mammary gland, uterus, bladder, lymph node, liver, small intestine, caecum, lung, thymus, colon, kidney, skin, heart and brain.

Animals↗

PubMed1999

Automating the supply chain in the OR.

At the University of Louisville (Ky) Hospital, staff members from the materials management and surgery departments have worked together to automate the supply chain. The goals were to remove supply activities from clinical staff members whenever possible, obtain and apply information for better product ordering and use, reduce personnel in the materials management department, and improve perioperative nurses' ability to obtain supplies--all at a decreased cost to the facility. This article describes how, after implementing point-of-service technology for all surgical supplies, the facility realized a cost-per-procedure savings of 16% and increased satisfaction among staff members in both departments.

Automation↗

PubMed1999

Functional roles for PECAM-1 (CD31) and VE-cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels.

Various in vitro models have been described that emulate one or more of the processes involved in angiogenesis in vivo. In the present study endothelial cells were cultured in three-dimensional type I collagen lattices in the presence of a mixture of basic fibroblast growth factor, vascular endothelial cell growth factor, and phorbol myristate acetate. Under these conditions, the endothelial cells rapidly assemble into an interconnected network of tube-like structures with a high frequency of intercellular canals or lumens. The formation of the networks and lumens was completely blocked by cycloheximide and by actinomycin D. Monoclonal antibodies directed against CD31 or vascular endothelial cadherin (VE-cadherin) inhibited the formation of endothelial tubes. A subtle difference in the morphology of cells treated with anti-CD31 versus anti-VE-cadherin was noted; namely, cells incubated in the presence of CD31 antibodies were rounded or formed attenuated tube-like structures, both of which were characterized by a single, large intra- or intercellular vacuole. In contrast, tube formation by cells incubated in the presence of VE-cadherin antibodies was also impaired and, most notably, demonstrated a reduction in either vacuole formation or vacuole fusion, depending upon the monoclonal antibody used. We suggest that the two endothelial-junction-associated proteins, CD31 and VE-cadherin, play different roles in the process of tube formation. CD31 appears to be required for cell elongation, migration, and/or invasion in the gels as well as for cell-cell association to form the network structures. VE-cadherin also appears to be required for cell-cell association, but additionally appears to play some role in the process of vacuolization or vacuole fusion leading to intercellular lumen formation.

Antibodies, Monoclonal↗