Ethics and opportunity costs: have NICE grasped the ethics of priority setting?
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Academies and Institutes↗
Biomedical subjects
M Sheehan
Publications and source records attributed to M Sheehan.
New transtracheal bronchoalveolar lavage technique for the diagnosis of respiratory disease in sheep.
A new transtracheal bronchoalveolar lavage technique for the diagnosis of respiratory disease in sheep under field conditions was tested in 76 sheep. The sheep were divided into three groups, normal sheep, sheep with clinical signs of respiratory disease and housed sheep, on the basis of their respiratory disease history and husbandry conditions. The detection of Mannheimia haemolytica and Mycoplasma ovipneumoniae or parainfluenza virus type 3 and bovine respiratory syncytial virus antigen in the lavage samples was closely correlated with clinical disease. The sheep with clinical respiratory disease had a higher mean percentage of neutrophils in the lavage fluid than the sheep in the other two groups.
Animal Husbandry↗
Healthy diet in primary care: views of general practitioners and nurses from Europe.
BACKGROUND: Most of the national colleges of general practitioners (GPs) do not have their own dietary/nutritional tools, and GPs and nurses do not have the time, knowledge, or skills to advise their patients about desirable dietary practices. OBJECTIVE: To assess the usefulness of a simple and practical guide on healthy diet to be used by European GPs and nurses. DESIGN: A postal survey was mailed to 171 GPs and nurses from 12 European countries to obtain information about the usefulness of a guide on healthy diet developed by EUROPREV. RESULTS: The perception of health professionals is that the main source of information on healthy diet for the population was the media. In all, 95% of GPs and nurses reported that the guide was useful; 93, 95, and 82% reported that the concepts were concise, easy to understand, and realistic, respectively. Also, 77% reported that the type of counselling recommended was feasible and could be applied, 94% reported that the implementation measures proposed could be effective and 88% reported that the Traditional Mediterranean Diet Pyramid is useful, but some concerns about the content were mentioned. CONCLUSIONS: GPs and nurses from Europe think that a practical guide on healthy diet developed by EUROPREV could be used to advise patients in primary care, although the Traditional Mediterranean Diet Pyramid should be modified.
Adult↗
Relation between Gram-stain and clinical criteria for diagnosing bacterial vaginosis with special reference to Gram grade II evaluation.
The aim of this study was to analyse how the results of Gram-staining vaginal smears correlated with the clinical criteria for determining the existence of bacterial vaginosis (BV) and, in particular, how the category defined as 'intermediate' or Gram grade II did so and its significance. Women attending an antenatal clinic with an abnormal vaginal flora, that is those who had Gram-stains of grades II or III, the latter considered to equate with BV, were given clindamycin or a placebo intravaginally and examined again on up to three occasions. Gram-stain readings of grade III correlated with the clinical criteria for BV on 356 (91.7%) of 388 occasions. Grade II readings covered the spectrum of clinical criteria and correlated with those for BV on 35 (37.2%) of 94 occasions. Grade I, recorded 231 times and seen usually after clindamycin treatment, was associated with BV only once. The sensitivity, specificity, positive predictive value and negative predictive value of the Gram stain for the diagnosis of BV, based on a combination of grades II and III, were 99.7%, 71.6%, 81% and 99.6%, respectively; based on grade III only, the values were 99.7%, 87.7%, 91.6% and 99.6%, respectively. Women reported a malodorous vaginal discharge on 49.2% of the occasions a grade III flora was seen and 13.3% of the times grade II was recorded. It was not associated with grade I and would seem a useful adjunct to the accepted clinical criteria for diagnosing BV. Each of the clinical criteria was found in about equal proportions (87%-91%) for women whose Gram grade was III. For grade II, an increased discharge was noted most often (76.5%) and 'clue' cells least often (24.5%). A positive amine test was the most specific, being associated with <1% of grade I smears. Of women with grade III status, 91% reverted to grade I after treatment with clindamycin for three days. In contrast, of women with grade II status, 53% reverted to grade I, as did 47% of those who were given a placebo. The 'intermediate' (grade II) category is a Gram-stain diagnosis and not one that can be made clinically. It is important to recognize as a distinct entity not only because amalgamation with grade III diminishes the specificity and positive predictive value of the Gram-stain for diagnosing BV, but also because women of grade II status usually fail to respond to clindamycin treatment, whereas those of grade III do not.
Bacteria↗
Protective effects of isohelenin, an inhibitor of nuclear factor kappaB, in endotoxic shock in rats.
Recent in vitro studies have shown that isohelenin, a sesquiterpene lactone, inhibits the NF-kappaB pathway. This study examines the effect of isohelenin in endotoxic shock induced by administration of Escherichia coli endotoxin in male Wistar rats. A group of rats received isohelenin (2 mg/kg intraperitoneally) 15 min before endotoxin. In vehicle-treated rats, administration of endotoxin caused severe hypotension, which was associated with a marked hyporeactivity to norepinephrine and acetylcholine in ex vivo aortas. Elevated levels of plasma nitrate/nitrite, metabolites of nitric oxide (NO), were also found. These inflammatory events were preceded by cytosolic degradation of inhibitor-kappaBalpha (IkappaBalpha) and activation of nuclear factor-kappaB (NF-kappaB) in the lung within 15 min of endotoxin administration. Treatment with isohelenin resulted in hemodynamic improvement and reduced plasma levels of NO metabolites. Nuclear translocation of NF-kappaB was inhibited by isohelenin treatment in the lung, whereas degradation of IkappaBalpha was unchanged. In a separate set of experiments, treatment with isohelenin significantly improved survival in mice challenged with endotoxin. We conclude that isohelenin exerts beneficial therapeutic effects during endotoxic shock through inhibition of NF-kappaB.
Acetylcholine↗
Multisite evaluation of a new dipstick for albumin, protein, and creatinine.
The goal of our study was to perform a multisite evaluation of a new urine dipstick called Multistix PROtrade mark (Bayer, Elkhart, IN), which has reagent pads for the simultaneous assay of urinary albumin, protein, and creatinine. Patients' urine specimens were assayed at four sites with these dipsticks and with the familiar Bayer Multistix 10SG dipsticks for protein. The new dipstick pads for albumin are impregnated with bis (3',3"-diiodo-4',4"-dihydroxy-5',5"-dinitrophenyl)-3,4,5,6-tetrabromo-sulfonephthalein (DIDNTB) dye. These dipsticks also have a novel pad that estimates urinary creatinine using the peroxidase activity of the copper-creatinine complex. We determined the interlaboratory agreement of these dipsticks by comparing dipstick results to values obtained by quantitative analytical methods. We found that dividing the dipsticks' albumin or protein results by the creatinine concentration reduced the number of false-positive albumin or protein values observed in concentrated urines, and reduced the number of false negatives in dilute urines. The ratio of albumin to creatinine, or protein to creatinine gives a better measure of albumin or protein excretion. Compared to reading by eye, the dipstick results agreed better with the quantitative assays when they were read by a reflectometer (Bayer Clinitek).
Albumins↗
Albuminuria and proteinuria in hospitalized patients as measured by quantitative and dipstick methods.
We tested patients' urines for albumin, protein, and creatinine by quantitative and dipstick methods. The concentrations of these analytes were established by quantitative, cuvet-based chemistry methods that we assumed gave the "correct" values. There was good to excellent agreement of the dipstick results with the quantitative methods for the above three analytes. We found many patients who excreted pathological amounts of albumin and/or protein who did not have a diagnosis of kidney disease or other likely causes of proteinuria, suggesting that albuminuria and/or proteinuria were underdiagnosed in our group of patients. Those with cardiovascular disease, kidney disease, or diabetes showed the greatest predictive value of a positive test for albumin or protein by dipstick. Dipstick testing for albumin, protein, and creatinine had good or excellent agreement with quantitative methods. The dipstick tests were easy to use, simple, and low in cost, and can serve well for point-of-care testing.
Albuminuria↗
"You become really close... you talk about the silly things you did, and we laugh": the role of binge drinking in female secondary students' lives.
In Australia, negative attitudes regarding young women's drinking have eased, drinking is on the increase, and there are heightened concerns about 'heavy' or 'binge' drinking. In a climate where underage drinking is frequently considered undesirable, campaigns aimed at reducing 'heavy' alcohol use have failed. This article takes as its departure point the notion that alcohol plays a meaningful role in social lives and relationships. It is through the use of narrative that these young women make sense of their drinking, which is still stigmatized. Any harm encountered along the way tends to be filtered through the 'good story,' brimming with tales of fun, adventure, bonding, sex, gender transgressions, and relationships. Nevertheless, these women implemented their own practical harm minimization strategies, and it is here that professionals can gain a foothold and assist young people and help them to drink more safely.
Adolescent↗
Tissue viral load variability in chronic hepatitis C.
OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.
Adult↗
Innexins in C. elegans.
Innexins are functionally analogous to the vertebrate connexins, and the innexin family of gap junction proteins has been identified in many invertebrates, including Drosophila and C. elegans. The genome sequencing project has identified 25 innexins in C. elegans. We are particularly interested in the roles that gap junctions may play in embryonic development and in wiring of the nervous system. To identify the particular C. elegans innexins that are involved in these processes, we are examining their expression patterns using specific antibodies and translational GFP fusions. In addition we are investigating mutant, RNAi and overexpression phenotypes for many of these genes. To date, we have generated specific antibodies to the non-conserved carboxyl termini of 5 innexins. We have constructed GFP translational fusions for 17 innexins and observed expression patterns for 13 of these genes. In total we have characterized expression patterns representing 14 innexins. Mutations have been identified in 5 of these genes, and at least 3 others have RNAi mutant phenotypes. Generalities emerging from our studies include: 1) most tissues and many individual cells express more than one innexin, 2) some innexins are expressed widely, while others are expressed in only a few cells, and 3) there is a potential for functional pairing of innexins.
Animals↗
Development and implementation of an information management and information technology strategy for improving healthcare services: a case study.
PeaceHealth is a multistate, not-for-profit integrated delivery network that owns and operates five acute care hospitals, one critical access hospital, and twenty-five outpatient clinics. PeaceHealth employs approximately two hundred physicians and seventy allied health professionals; it has relationships with one thousand affiliated physicians. In 1990, PeaceHealth developed a set of strategic priorities for delivering seamless care across the continuum, and creating partnerships between caregivers and patient-consumers. A major component of these strategies was development and implementation of the technology, knowledge, organizational, and community infrastructures that would support delivering and using high-quality, timely information when and where it is needed for effective clinical, operational, and financial decision making. Executing this strategy has resulted in implementation of standard enterprisewide information systems, including a computer-based patient record system in inpatient and outpatient settings, tactical and strategic decision support systems, a well-developed intranet and access to the Internet, and a knowledgeable workforce that have enabled PeaceHealth to support and improve its services and business by bringing interactive information directly to patients, caregivers, managers, directors, and executives. This case study discusses the drivers behind the development of this strategy, specific components of the information management and information technology infrastructure, examples of the impact they have had on patients, caregivers, and the organization, and lessons learned.
Computer Communication Networks↗
Characterization of cDNAs differentially expressed in roots of tobacco (Nicotiana tabacum cv Burley 21) during the early stages of alkaloid biosynthesis.
A set of 60 cDNAs were isolated by subtractive hybridization screening of a phage library using radioactively-labeled probes generated from root mRNAs isolated from tobacco (Nicotiana tabacum cv Burley 21) plants before and 3 days after topping. Among the differentially expressed gene products were full-length and partial cDNAs encoding arginine decarboxylase (ADC), ornithine decarboxylase (ODC), and S-adenosylmethionine synthetase (SAMS), enzymes involved in polyamine and alkaloid biosynthesis. The other cDNAs isolated were placed into one of several categories and encode metabolic enzymes, proteins involved in transcription and translation, components of signal transduction pathways, and homologs of genes whose expression has been shown to be regulated by phytohormones (i.e. auxin, ABA), wounding or other stress responses. RNA gel blot analysis showed that the ADC and ODC transcripts were preferentially expressed in the roots and floral tissues of mature tobacco plants, whereas SAMS transcripts were detected in all tissues examined. The steady-state levels of the ADC and ODC mRNAs increased in the roots of wild-type tobacco plants during the 24 h period after topping, whereas little change was observed in the abundance of the SAMS transcripts in these tissues. The possible factors associated with the regulation of expression of these genes are discussed.
Journal Article↗
The increasing problem of unusual pancreatic tumors.
HYPOTHESIS: Patients presenting with a pancreatic mass often have a curable lesion rather than the more common adenocarcinoma. Greater awareness of this among nonsurgeons is necessary. DESIGN: Retrospective case series. SETTING: Tertiary care referral hospital. PATIENTS: All patients who presented with a pancreatic mass during the 8 years from 1990 to 1998 were studied. Patients with a history of chronic pancreatitis, a functioning pancreatic neuroendocrine tumor, or pancreatic adenocarcinoma were excluded. Forty patients were identified, demographic and clinical characteristics recorded, and long-term follow-up obtained. INTERVENTIONS: Therapy included either a Whipple procedure or distal pancreatectomy. Two patients underwent a biliary bypass. MAIN OUTCOME MEASURES: Tumor histology, morbidity, and survival. RESULTS: Three hundred thirty-six patients with a pancreatic mass were treated during this 8-year period. Two hundred ninety-six of these had pancreatic adenocarcinoma. Forty (11.9%) of the 336 patients had other types of pancreatic tumors. Two thirds of these patients were female, with an average age of 57 years. Seventy-five percent of these tumors were either malignant or potentially malignant. In several instances, cystic tumors were diagnosed as inflammatory pseudocysts and managed accordingly. Fourteen (35%) of 40 patients had no symptoms and their tumor was found on a computed tomographic scan performed for another indication. Percutaneous biopsy was performed in 9 patients, of whom 5 were assigned an incorrect diagnosis. There were no operative deaths, although the postoperative complication rate was 23%. CONCLUSIONS: In this series, nearly 12% of patients presenting with a pancreatic mass did not have pancreatic adenocarcinoma, but rather more favorable lesions amenable to operation. Preoperative biopsy should not be carried out. Curative procedures can be safely performed in centers seeing a large number of patients with pancreatic tumors, and the long-term results of extirpation are excellent.
Adenocarcinoma↗
Natural fluctuations of hepatitis C viral load in a homogeneous patient population: a prospective study.
The aim of this study was to determine the variation in hepatitis C viral load over an extended period of patient follow up. Serum samples were collected from 49 female individuals who were identified as having been infected from the same source of hepatitis C-contaminated anti-D immunoglobulin during the period from 1977 (May) to 1978 (November). All patients attended the hepatitis C clinic at Cork University Hospital, Cork, Ireland. The study group was homogeneous with respect to gender, hepatitis C virus (HCV) genotype (1b), and duration of infection. None of the patients had received antiviral therapy at the time of completion of study. Viral load quantifications were assessed using the Roche Monitor (F. Hoffmann-La Roche, Ltd., Basel, Switzerland) assay. The mean age of the study group at time of infection was 30.3 years (SD +/- 6.1) with a range from 18.5 to 43 years. The mean time of follow-up was 4. 1 years (SD +/- 1.0) with a range from 1.2 to 5 years. The mean rate of change of viral load per year was 0.23 log(10) viral copies per mL serum for the study group (SD +/- 0.19) with a range of -0.18 to 0.78 that was significantly different from zero, P < 10(-10). The rate of change of viral load per year was negatively correlated with viral load at first determination, r = -.35, P =.01. Age at infection did not correlate with the slope of change of viral load, P =.10. In conclusion, most women infected with HCV 1b will have an increase in viral load over time but a few patients who acquire infection early in adult life will show a decrease in viral load.
Adolescent↗
Linking manager values and behavior with employee values and behavior: a study of values and safety in the hairdressing industry.
Five theoretical processes that link values and behavior were identified: value congruence, value-behavior consistency, behavioral modeling, value internalization, and descriptive norms. A values questionnaire was administered to 219 employees and their managers. Values for preventive safety procedures and time urgency were linked to safety behavior of employees in the hairdressing industry. Hairdressers are frequently exposed to hazardous chemicals, and the safety behavior measured was wearing protective gloves. Results support value internalization (linking manager's and employee's values) and behavioral modeling (linking manager's and employee's behavior). Employee time urgency values were also negatively related to safety behavior (value-behavior consistency). Descriptive norms and value congruence were not supported. Strategies to align values within organizations and the management of safety at work are considered.
Adult↗
Goals and strategies for teaching death and dying in medical schools.
Teaching medical students to respond to needs of the dying represents an important challenge for medical educators. This article describes the goals and objectives that should be identified before medical schools can meet this challenge, as well as strategies that, when implemented, will provide students with the necessary knowledge, skills, and attitudes to meet the needs of the dying patients. The goals and objectives were identified through a modified group consensus process developed during Choice In Dying's 5-year project "Integrating Education on Care of the Dying into Medical Schools." The authors have diverse experiences and backgrounds and are actively involved in death and dying teaching at 11 medical schools. They conclude that after accepting the goals and objectives, key medical school faculty can work cooperatively to develop strategies to integrate them into the school's curriculum. Without first establishing a set of goals and objectives and developing evaluation methods, medical schools could miss their mark in fostering the student's ability to care for the dying.
Journal Article↗
Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women.
OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen.
Adult↗
Comparative analysis of the efficacy of A1 adenosine receptor activation of Gi/o alpha G proteins following coexpression of receptor and G protein and expression of A1 adenosine receptor-Gi/o alpha fusion proteins.
HEK293T cells were transiently transfected to express either the human A1 adenosine receptor together with pertussis toxin-resistant cysteine-to-glycine forms of the alpha subunits of Gi1 (C351G), Gi2 (C352G), and Gi3 (C351G) and wild-type Go1alpha or fusion proteins comprising the A1 adenosine receptor and these Gi/o G proteins to compare A1 adenosine receptor agonist-mediated activation of these Gi family G proteins upon coexpression of individual Gi/o G proteins and receptor versus expression as receptor-G protein fusion proteins. Addition of the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) to membranes of pertussis toxin-treated cells resulted in a concentration-dependent stimulation of [35S]GTPgammaS binding with comparable amounts of NECA required to produce half-maximal stimulation following transfection of A1 adenosine receptor and Gi/o G proteins either as fusion proteins or as separate polypeptides. However, the magnitude of agonist-mediated activation of GTPgammaS binding was greatly enhanced by expressing the A1 adenosine receptor and Gi family G proteins from chimaeric open reading frames. This observation was consistent following the study of more than 40 agonists. No preferential activation of any G protein was observed with more than 40 A1 receptor agonists following cotransfection of receptor with G protein or transfection of receptor-G protein fusion proteins. These studies demonstrate the utility of using fusion proteins to study receptor-G protein interaction, show that the A1 adenosine receptor couples equally well to the Gi/o G proteins Gi1alpha, G i2alpha, Gi3alpha, and Go1alpha, and demonstrate that for a range of agonists there is no selectivity for activation of any particular A1 adenosine receptor-Gi/o G protein combination.
Adenosine-5'-(N-ethylcarboxamide)↗