Unexplained illness among injecting drug users in Dublin: a case-control study.
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Adult↗
Biomedical subjects
M Ward
Publications and source records attributed to M Ward.
Value of antimicrobials in the prevention and treatment of tuberculosis in the United States.
OBJECTIVE: To estimate the economic value of antimicrobials for the prevention and treatment of tuberculosis in the United States from 1954 through 1997. DESIGN: Published sources were used to estimate the burden of illness (direct medical costs, reductions in quality of life, and years of life lost) from active tuberculosis (TB) cases diagnosed between 1954 and 1997. Published literature concerning the pre-antimicrobial incidence rate and treatment of TB were extrapolated to estimate the burden of illness that would have occurred in the absence of antimicrobials. RESULTS: Between 1954 and 1997, the use of antimicrobials reduced the number of newly diagnosed cases of active TB by 32% (relative to the number that would have occurred in the absence of antimicrobials), the number of mortalities by 81%, the number of life-years lost by 87%, and the cost of medical treatment by 76%. The total financial burden of illness over this time period (including the value of lost life-years) was reduced from $894 billion (in 1997 dollars) to $128 billion. CONCLUSION: TB antimicrobials had a substantial health impact in the US from 1954 to 1997. This quantitative assessment of the economic impact of innovative biopharmaceutical products demonstrates the importance of continuing medical innovation.
Antibiotics, Antitubercular↗
Optimal activated clotting time during percutaneous coronary intervention.
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Angioplasty, Balloon, Coronary↗
Molecular cloning, gene organization and expression of rainbow trout (Oncorhynchus mykiss) inducible nitric oxide synthase (iNOS) gene.
A full-length inducible nitric oxide synthase (iNOS) gene has been sequenced for the first time outside the mammals, and the gene organization compared with that already determined for human iNOS. While there are some differences from the human gene, overall the exons show remarkable conservation in sequence and organization. As in human, the trout iNOS gene has 27 exons, with 18 of the trout exons being identical in size with the equivalent human exons. The cofactor-binding domains are found in the same exons and in some cases are absolutely conserved. Differences include the start of the ORF in exon 3 instead of exon 2, resulting in a deletion at the 5' end of the trout iNOS protein. Exon 27 also shows a large difference in size and although the trout exon is larger this is due to the length of the 3'-UTR. Several non-mammalian features are notable, and include a conserved potential glycosylation site in chicken and fish, and an insertion at the boundary of exons 20 and 21 in fish. The intron sizes in trout were generally much smaller than in human iNOS, making the trout iNOS gene approximately half the size of the human gene. Analysis of RNA secondary structure revealed two regions with complementarity, which could interfere with reverse transcription. Using a trout fibroblast cell line (RTG-2 cells), it was shown by reverse transcriptase (RT)-PCR that virus infection was a good inducer of iNOS expression. However, when using a combination of Superscripttrade mark II for reverse transcription and primers at the 5' end of the gene only very weak products were amplified, in contrast with the situation when primers at the 3' end of the gene were used, or ThermoScripttrade mark-derived cDNA was used. The impact of such results on RT-PCR analysis of iNOS expression in trout is discussed.
Amino Acid Sequence↗
Genetic engineering of the Trichoderma reesei endoglucanase I (Cel7B) for enhanced partitioning in aqueous two-phase systems containing thermoseparating ethylene oxide--propylene oxide copolymers.
Endoglucanases (endo-1,4-beta-D-glucan-4-glucanohydrolase, EC 3.2.1.4) are industrially important enzymes. In this study endoglucanase I (EGI or Cel7B) of the filamentous fungi Trichoderma reesei has been genetically engineered to investigate the influence of tryptophan rich peptide extensions (tags) on partitioning in an aqueous two-phase model system. EGI is a two-domain enzyme and is composed of a N-terminal catalytic domain and a C-terminal cellulose binding domain, separated by a linker. The aim was to find an optimal tag and fusion position, which further could be utilised for large scale extractions. Peptide tags of different length and composition were attached at various localisations of EGI. The fusion proteins were expressed from T. reesei with the use of the gpdA promoter from Aspergillus nidulans. Variations in secreted levels between the engineered proteins were obtained. The partitioning of EGI in an aqueous two-phase system composed of a thermoseparating ethylene oxide-propylene oxide random copolymer (EO(50)PO(50)) and dextran, could be significantly improved by relatively minor genetic engineering. The (Trp-Pro)(4) tag added after a short stretch of the linker, containing five proline residues, gave in the highest partition coefficient of 12.8. The yield in the top phase was 94%. The specific activity was 83% of the specific activity of unmodified EGI on soluble substrate. The efficiency of a tag fused to a protein is shown by the tag efficiency factor (TEF). A hypothetical TEF of 1.0 would indicate full tag exposure and optimal contribution to the protein partitioning by the fused tag. The location of the fusion point after the sequence of five proline residues in the linker of EGI is the most beneficial in two-phase separation. The highest TEF (0.97) was obtained with the (Trp-Pro)(2) tag at this position, indicating full exposure and intactness of the tag. However, the peptide tag composed of (Trp-Pro)(4) improved the partition properties the most but had lower TEF in comparison to (Trp-Pro)(2).
Base Sequence↗
Genetically engineered peptide fusions for improved protein partitioning in aqueous two-phase systems. Effect of fusion localization on endoglucanase I of Trichoderma reesei.
Genetic engineering has been used for fusion of the peptide tag, Trp-Pro-Trp-Pro, on a protein to study the effect on partitioning in aqueous two-phase systems. As target protein for the fusions the cellulase, endoglucanase I (endo-1,4-beta-Dglucan-4-glucanohydrolase, EC 3.2.1.4, EGI, Cel7B) of Trichoderma reesei was used. For the first time a glycosylated two-domain enzyme has been utilized for addition of peptide tags to change partitioning in aqueous two-phase systems. The aim was to find an optimal fusion localization for EGI. The peptide was (1) attached to the C-terminus end of the cellulose binding domain (CBD), (2) inserted in the glycosylated linker region, (3) added after a truncated form of EGI lacking the CBD and a small part of the linker. The different constructs were expressed in the filamentous fungus T. reesei under the gpdA promoter from Aspergillus nidulans. The expression levels were between 60 and 100 mg/l. The partitioning behavior of the fusion proteins was studied in an aqueous two-phase model system composed of the thermoseparating ethylene oxide (EO)-propylene oxide (PO) random copolymer EO-PO (50:50) (EO50PO50) and dextran. The Trp-Pro-Trp-Pro tag was found to direct the fusion protein to the top EO50PO50 phase. The partition coefficient of a fusion protein can be predicted with an empirical correlation based on independent contributions from partitioning of unmodified protein and peptide tag in this model system. The fusion position at the end of the CBD, with the spacer Pro-Gly, was shown to be optimal with respect to partitioning and tag efficiency factor (TEF) was 0.87, where a fully exposed tag would have a TEF of 1.0. Hence, this position can further be utilized for fusion with longer tags. For the other constructs the TEF was only 0.43 and 0.10, for the tag fused to the truncated EGI and in the linker region of the full length EGI, respectively.
Amino Acid Sequence↗
Utility of mechanical rheolysis as an adjunct to rescue angioplasty and platelet inhibition in acute myocardial infarction and cardiogenic shock: a case report.
We describe the value of mechanical rheolysis as an adjunct to rescue angioplasty and platelet glycoprotein IIb/IIIa receptor inhibition in a patient with acute myocardial infarction and cardiogenic shock in whom the severity of the intracoronary thrombus burden precluded restoration of antegrade coronary flow by conventional balloon angioplasty and stenting.
Aged↗
Computational methods for single-point and multipoint analysis of genetic variants associated with a simulated complex disorder in a general population.
Several techniques for association analysis have been applied to simulated genetic data for a general population. We describe and compare the performance of three single-point methods and two multipoint approaches rooted in machine learning and data mining.
Alleles↗
The value and limitations of the arm cephalic and basilic vein for arteriovenous access.
The National Kidney Foundation has identified the use arteriovenous grafts (AVG) and the interventions required to maintain their patency as two major causes of increased expenditure in the management of hemodialysis access in end-stage renal disease patients. They have issued an appeal for the increased use of native arteriovenous fistulae (AVF). Although the radialcephalic AVF is considered to be the procedure of choice for these patients, other veins should be sought after to maintain an all-autogenous AVF policy. We examined our experience of using arm veins that were transposed to the brachial artery. Over the last 2.5 years, 109 brachiocephalic AVF (BCAVF) and 63 brachiobasilic AVF (BBAVF) were placed in 163 patients with chronic renal failure. In each group, 40 and 25 patients were males, respectively. Ages ranged from 29 to 88 years (mean 67+/-1.4 years) and 37 to 84 years (mean 69+/-2.0 years) in each group. Diabetic patients comprised 56 and 65% of each group and hypertensive patients comprised 73 and 75% of each group. Data collection was via chart review, personal interviews, and review of the dialysis records. Patency was assessed by life-table analysis. The log-rank test was performed in conjunction with Kaplan-Meier survival analysis. Our results showed that the use of BCAVF and BBAVF appears to be a viable alternative to prosthetic arteriovenous grafts. On the basis of our experience, an algorithm for placement of AVF is suggested.
Adult↗
Improving nurse retention in the National Health Service in England: the impact of job satisfaction on intentions to quit.
In recent years the British National Health Service (NHS) has experienced an acute shortage of qualified nurses. This has placed issues of recruitment and retention in the profession high on the political agenda. In this paper, we investigate the determinants of job satisfaction for nurses and establish the importance of job satisfaction in determining nurses' intentions to quit the NHS. We find that nurses who report overall dissatisfaction with their jobs have a 65% higher probability of intending to quit than those reporting to be satisfied. However, dissatisfaction with promotion and training opportunities are found to have a stronger impact than workload or pay. Recent policies, which focus heavily on improving the pay of all NHS nurses, will have only limited success unless they are accompanied by improved promotion and training opportunities. Better retention will, in turn, lead to reduced workload.
Adult↗
Advanced life support skills undertaken by nurses--UK survey.
Many nurses successfully complete the Resuscitation Council (UK), European Resuscitation Council, advanced life support (ALS) Provider Course. Acquiring ALS provider status is not necessarily a licence to practice and individual hospital policy determines which skills these nurses can then perform without direct medical supervision. This postal survey aimed to determine which ALS skills are utilised by nurse ALS providers working in a variety of clinical areas within acute hospitals in the UK. A questionnaire was sent to the Resuscitation Officer or Nursing Director of all acute hospital groups in the UK. Almost 261 (87%) of the questionnaires were completed and returned. Nurse ALS providers in 99% of coronary care units, 89% of intensive care units, and 88% of accident and emergency departments undertook manual defibrillation. The majority of hospitals ran compulsory in-house training sessions for intravenous cannulation. Laryngeal mask insertion by nurse ALS providers was permitted in 19% of coronary care units and in the wards of 16% of the responding hospitals. Tracheal intubation by nurse ALS providers working in coronary care units, intensive care units and emergency departments was permitted by 11% of the responding hospitals. This survey has demonstrated that many acute hospitals do not permit nurse ALS providers to use a number of the skills taught on the ALS provider course. General ward-based nurse ALS providers, in particular, are restricted in the ALS skills, they are permitted to use. It would be more efficient for nurses to be trained and assessed specifically in skills they are then permitted to use. Having been assessed in a given skill and achieved a nationally recognised standard, nurse ALS providers should be permitted to use it in clinical practice.
Catheterization↗
Combined upper and lower extremity deep venous thrombosis.
In order to elucidate the natural history of upper extremity deep venous thrombosis (UEDVT), we compared the morbidity and mortality of patients with UEDVT and that of patients with both UEDVT and lower extremity deep venous thrombosis (LEDVT). Between 1993 and 1996, 21 patients presented to our institution with both LEDVT and UEDVT (Group 1). During the same time period, 144 patients were diagnosed with UEDVT alone (Group 2). The diagnosis was confirmed by duplex scanning in all patients. In Group 1, there were 14 females (67%) and 7 males (23%) with ages ranging from 25 to 97 yr old [mean 73 yr old +/-17 yr (SD)]. In Group 2, there were 84 females (58%) and 60 males (42%) with ages ranging from 9 to 101 yr old [mean 67 yr old +/-17 yr (SD)]. Differences in age and sex between the two groups were not statistically significant. In Group 1, systemic anticoagulation was implemented in 17 patients (81%). Two patients (9.5%) required placement of a SVC and IVC filters due to contraindication to anticoagulation. One patient did not receive anticoagulation, and one patient was only started on aspirin. In Group 2, treatment consisted of systemic anticoagulation in 94 patients (65%). The remainder of the patients were treated with aspirin in three patients (2%) or no anticoagulation in 31 patients (19%). Sixteen patients (11%) underwent placement of a SVC filter either due to failure of anticoagulation to prevent pulmonary embolism (two patients) or contraindication to anticoagulation (14 patients). Pulmonary emboli were documented by ventilation/perfusion lung scan in two patients (9.5%) in Group 1 and in 16 patients (11%) in Group 2. In the first group, 8 of the 21 patients (38%) were dead within 1 month of the diagnosis of UEDVT, and 11 of 21 patients (52%) were dead within 2 months of the diagnosis of UEDVT. In the second group, 20 of 144 patients (14%) were dead within 1 month of the diagnosis of UEDVT and 38 of 144 patients (26%) were dead within 2 months of diagnosis (P<0.02). Our data suggest that patients with both UEDVT and LEDVT have a higher mortality than patients with UEDVT alone. As the risk for pulmonary embolism is similar in both groups, we speculate that the severity of medical illness in patients with both UEDVT and LEDVT may contribute to the higher mortality. This is the first study to examine the mortality of this group of patients.
Adolescent↗
Effect of supplemental methionine on plasma homocysteine concentrations in healthy men: a preliminary study.
Hyperhomocysteinaemia is an established risk factor for vascular disease. The only source of homocysteine in humans is the amino acid methionine found in dietary protein. In an 8-week study, fasting plasma homocysteine concentrations were examined in a group of healthy male subjects (n = 6) under usual dietary conditions (weeks 1-4) and in response to weekly graded (25, 50 and 75 mg/kg/d) supplementary methionine (weeks 5, 6, 7). Nutrient intakes, including methionine, were calculated from 4 x 3 day food records. Under usual dietary conditions (mean methionine intake; 0.95 +/- 0.51 mg/d) weekly mean plasma homocysteine concentrations for the group were not significantly different (ANOVA) from each other ranging from 6.82 +/- 1.77 to 9.42 +/- 2.73 mumol/l. Doubling (supplementing with 25 mg/kg/d; + 2.04 g/d) or quadrupling (50 mg/kg/d; + 4.08 g/d) methionine intakes did not result in a significant increase in plasma homocysteine (8.56 +/- 3.68 mumol/l and 13.37 +/- 5.09 mumol/l respectively). A significant increase, however, was achieved when diets were supplemented with methionine at the highest level of 75 mg/kg/d (+6.14 g/d) resulting in a mean plasma homocysteine concentration of 18.05 +/- 11.8 mumol/l. Mean plasma homocysteine concentration returned to baseline (8.76 +/- 3.42 mumol/l), 10 days post-supplementation. The results of this study indicate that an increased dietary methionine will only cause elevated fasting homocysteine concentrations if ingested at intakes equivalent to five times usual intake. Because it is very unlikely that such levels could be achieved through dietary means alone we conclude that plasma homocysteine is unlikely to be affected by longer-term changes in food methionine intake.
Adult↗
Homocysteine, folate, and cardiovascular disease.
Cardiovascular disease (CVD) continues to be one of the main causes of mortality in the western world, however approximately only two-thirds of all episodes can be attributed to traditional environmental and genetic risk factors. Over the past decade it has emerged that a moderate elevation in plasma concentrations of the amino acid homocysteine (tHcy) constitutes a risk factor for atherosclerotic vascular disease in the coronary, cerebral and peripheral vessels. Furthermore, this association is a graded one with no apparent threshold and is independent of, but may enhance the effect of conventional risk factors. Plasma homocysteine is determined by both genetic and nutritional factors. The B-vitamins folate, B-12 and B-6 all play a key role in homocysteine metabolism and in fact it has been proposed that about two-thirds of all cases of hyperhomocysteinemia are due to an inadequate status of one or all of these vitamins. Of the three, folate appears to be the most important determinant and has been shown to significantly lower homocysteine concentration when administered at doses ranging from 0.2 to 10 mg/d in both healthy and hyperhomocysteinemia subjects. There is considerable variation in the rate of CVD mortality between northern and southern European countries. A common dietary element in regions with lower CVD incidence i.e. southern European countries appears to be the higher consumption of fruit and vegetables. In the past this protective effect of fruit and vegetables has been primarily attributed to antioxidants. Fruit and vegetables are however also one of the main sources of folate in the diet, contributing to more than 30% of total dietary folate intake (even in countries where consumption of fruit and vegetables is low). Thus, in light of the evidence that folate may play a role in primary prevention of CVD via homocysteine-lowering the protective effect of fruit and vegetables may be partly explained by folate.
Antioxidants↗
Failure of accommodation in patients with HIV infection.
PURPOSE: The principal objective was to test the hypothesis that HIV-positive patients have significantly reduced amplitudes of accommodation compared with controls. The secondary objective was to investigate accommodative impairment in relation to factors such as age of susceptibility, CD4 count, viral load and current antiretroviral therapies. METHOD: The study was a single-center open prospective study involving a subject population of 43 HIV-positive men aged from 26 to 39 years with no previous history of eye problems and 21 age-matched healthy male controls. The main outcome measure was the amplitude of accommodation, as measured monocularly with a standard push-up technique. RESULTS: Amplitudes of accommodation were significantly smaller in the HIV-positive group compared with controls for age groups 25-29 (p = 0.016) and 30-34 years (p = 0.030) but not in the older group. In total, 30% (8/27) of patients aged between 25 and 34 years had reduced amplitudes of accommodation below age-expected norms. Accommodative failure was not related to current or lowest CD4 count, viral load or specific antiretroviral therapies. CONCLUSION: This study has identified accommodative failure in a significant proportion of HIV-positive patients aged between 26 and 35 years. This problem may be under-recognised, and further studies are warranted to investigate possible causes.
Accommodation, Ocular↗
Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete.
BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.
Aged↗
Program logic. A planning and evaluation method.
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Accidental Falls↗
Middle school reform through data and dialogue. Collaborative evaluation with 17 leadership teams.
This report describes a 2-year, longitudinal study of one school district's effort to link site-based, collaborative evaluation with formal, centralized program evaluation. Participants formed a research team in partnership with a local university. Team members assisted leadership teams in identifying issues for informal, site-based assessments and then used the information to monitor progress toward established goals. Participants collaborated in designing and conducting informal assessments of student achievement, school climate and safety, discipline, and parent involvement. Leadership teams used these data in developing their school improvement plans. Researchers and administrators used these data to revise the districtwide survey. At the end of the 2-year cycle, analysis of school improvement plans showed that collaborative evaluation is creating a connection between dialogue and data. These 17 middle schools are approaching school improvement in a more integrated fashion by actively involving key stakeholders (students, parents, and teachers) in the evaluation process.
Adult↗