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Biomedical subjects

M Giacomini

Publications and source records attributed to M Giacomini.

At least 19 recordsLinked to original sources

Development of a piezoelectric immunosensor for the measurement of paclitaxel.

This paper describes the development of a piezoelectric immunosensor for the measurement of paclitaxel (taxol), a natural anti-cancer agent. An antibody specific for taxanes was immobilized onto the surface of quartz crystals by means of the layer-by-layer self-assembly technique. The immobilization was achieved using electrostatic interactions between a precursor layer and the antibody molecules. The assembly process was monitored by a quartz crystal microbalance (QCM) and the topography of the modified quartz crystals was investigated by means of atomic force microscopy. The specific interaction of the immobilized antibody with paclitaxel in solution at different concentrations was monitored as a change in resonant frequency of the modified crystal. Moreover, the influence of non-specific adsorption was also characterized. The results show that the proposed immunosensor offers a promising alternative to classical analytical methods for a fast and easy determination of paclitaxel.

Animals↗

Decision tools for life support: a review and policy analysis.

OBJECTIVE: To identify, describe, and compare published documents intended to guide decisions about the administration, withholding, or withdrawal of life support in critical care. DESIGN: Review article. SETTING AND SOURCES: Publicly available, English-language guidelines or decision tools for life support, identified through systematic literature search. MEASUREMENTS AND MAIN RESULTS: Forty-nine documents were included and coded for authorship, source, development methodology, format, and positions taken on 12 common life-support issues. Sources were independent academics (n=21, 43%), professional organizations (n=19, 44%), and provider organizations. Eighteen documents (37%) described no development method. Twenty-three (47%) were produced collectively (e.g., by committees or consensus conference), 7 (14%) mentioned a literature review, and 2 (4%) were based upon the author's professional experience. Tools differed in format and focus; we characterize three types as decision schemas (involving clinical practice algorithms; n=7, 14%), decision guides (reviewing legal or professional positions; n=29, 59%), and decision counsels (more discursive and focusing typically on ethical issues; n=13, 27%). Tools addressed 12 common life-support issues: advance directives (67%), resource considerations (51%), ICU discharge criteria (27%), ICU admission criteria (16%), whether withholding differs from withdrawing life support (59%), whether nutrition and hydration decisions are different from decisions about other types of life support (61%), euthanasia (49%), double effect (47%), brain death (35%), special considerations for patients in a persistent vegetative state (51%), potential organ donors (12%), and pregnant patients (10%). Positions on these key life-support issues varied. CONCLUSIONS: Published tools for guiding life-support decisions vary widely in their genesis, authorship, format, focus, and practicality. They also differ in their attention to, and positions on, key life-support dilemmas. Future research on decision tools should focus on how users interpret and apply the messages in these tools and their impacts on practice, quality of care, participant experiences, and outcomes.

Decision Support Techniques↗

An experience of microbiological data sharing.

OBJECTIVES: The control of infections and their resistance to antibiotics in hospitals is a matter of vital importance in the follow-up of transplant patients. This project has the purpose of translating microbiological reports from an obsolete file structure to a system which could guarantee a more correct and quick transmission of data, a system of storage which reduces the possibility of errors, a smoother manipulation, consultation and updating of data and, at least, a simple way to compute the cost of analysis, based on the costs determined by the national's DRG. METHODS: The proposed solution is a semiautomatic interface which translates these data into a relational database on a daily basis, interprets the requests coming from external centers and produces reports. The prospective to use this tool for several centers indicates to us the need to choose an HL7 output for the interface. RESULTS: A prototype version of this program was installed in February 2004. In this period, routine work has been recorded with an average of 6.5 samples per day, with a maximum of 23 samples. Moreover, historical data from 1998 has been translated. The main source of errors in these data was due to patient identification problems with an average occurrence of 4.06% in the virology section and of 4.16% in the microbiological division. CONCLUSIONS: A complete reorganization of the system would be desirable but at the moment it is not realistic because of obvious budget problems. The proposed approach, mainly the HL7 interface, seems to be a reasonable compromise.

Cross Infection↗

Metabolic treatment of critically ill patients: energy expenditure and energy supply.

Nutrition in critically ill patients should be considered as therapy: assessing the energy expenditure and the termogenic effect of food, and knowing the differences among composition and amount of given substrates, it is possible restore, maintain, or at least limit the derangement of energy equilibrium. Energy metabolism comprehends assumption, storage and oxidation of nutrients: all these factors could be discriminant in critical clinical conditions, particularly cardiac and respiratory failure. Then, this review would lead the decision making process beginning from biochemistry and bioenergetics, until the metabolic strategy practically usable at the bedside of patients during the whole critical phase of their pathology.

Critical Illness↗

[Non invasive mechanical ventilation in acute cardiogenic pulmonary edema: is it all done?].

The aim of the paper is to critically analyse the results obtained by recent literature concerning the most important aspects of application of Non Invasive Mechanical Ventilation for the treatment of Acute Cardiogenic Pulmonary Edema, and to elaborate a definition of what is, on the whole, widely accepted, focusing the attention on those issues which still remain unanswered and therefore require further studies. MEDLINE was searched and the bibliography of a selected group of articles was perused. The literature was analysed and the information gathered has proved to address the questions in a systematic way. All studies concerning the use of a non invasive ventilation technique in the treatment of acute pulmonary edema or acute respiratory failure which included pulmonary edema have been considered. New physiological issues have been introduced on the pathogenesis of acute pulmonary edema. Even though very little non invasive ventilation has been performed outside intensive care units, a growing interest is rising in the opportunity of transferring this technique to a different setting which would include critically ill patients. No random controlled trials and studies have ever established whether positive pressure support is really better than continuous airway pressure, but several trials appear to have excluded the potential for high-risk in the use of assisted ventilation. General opinion has not yet confirmed foreseeable failures in non invasive ventilation at the time of patient admission. A good deal of favorable experimental evidence supports the use of non invasive ventilation in the acute pulmonary edema and guarantees safety when used in intensive care units. Very few trials have been carried out in order to explore application on severe pulmonary edema outside intensive care unit. A whole new world of old and new issues on patient selection criteria, ventilation times, type of ventilation and predictability of failure, could be discovered.

Acute Disease↗

Tailoring biomaterial compatibility: in vivo tissue response versus in vitro cell behavior.

Biocompatibility relies essentially on surface phenomena, represented by cell-cell, cell-material and material (polymer)-protein interactions. An in vivo and in vitro experimental investigation was carried out on the biomaterials of two different classes with a good potential for in situ utilisation. Non-resorbable (Polypyrrole, Polyaniline, Polyimide) and resorbable (PLLA-PDXO-PLLA) materials for tissue engineering were studied for their overall tissue tolerance and cellular interactions. These non-resorbable polymers conceived for biosensor applications and implantable drug-delivery systems are intrinsically conductive. The PLLA-PDXO-PLLA triblock copolymer showed interesting tensile properties for bone and cartilage tissue engineering due to the presence of 1,5-dioxepan-2-one. In vitro and in vivo parallel studies showed an interesting correspondence: a) the cells in contact with the resorbable material that appeared to be capable of migratory-regenerative aspects in vitro exhibited good compatibility in vivo; whereas b) the non-resorbable materials, which are designed to remain in situ in vivo, were seen to have the potential to represent an adverse factor (inflammation, fibrotic reactions) that correlated with some aspects of cell behaviour in vitro.

Absorbable Implants↗

Non-invasive mechanical ventilation in patients with acute cardiogenic pulmonary edema.

AIM: To evaluate the use of noninvasive mechanical ventilation (NIMV) in patients with acute cardiogenic pulmonary edema. METHODS DESIGN: prospective study. SETTING: Emergency Department at a University hospital. PATIENTS: 84 patients with acute respiratory distress due to pulmonary edema. Interven-tions: NIMV, using a pressure support mode and positive end-expiratory pressure (PEEP). A "weaning test" to evaluate clinical stability. MEASUREMENTS: heart rate, arterial blood pressure, respiratory rate, arterial blood gases, electrocardiogram and incidence of myocardial infarction before and after NIMV. Mortality and duration of hospital stay were also considered. RESULTS: A total of 84 patients received NIMV with 14+/-3.6 cm H2O pressure support over PEEP of 8.3+/-2.1 cm H2O and FiO2 1. At the end of the study period, 16 patients (19%) were considered "non responders" and required invasive ventilation; 62 patients (74%) were considered "responders" and subsequently transferred to the medical ward. The hospital mortality was 14% and 25% in the "responder" and "non responder" groups, respectively; the length of stay was 15.7+/-10.1 days in the "responder" group vs 16+/-10.6 days in the "non responder" group. We never found new episodes of myocardial infarction related to NIMV. The only significant difference between "responder" and "non responder" patients was arterial blood pressure. CONCLUSIONS: We hypothesize that "non responder" patients, characterized by blood pressure values lower than "responders", are less "cardiocompetent" and thus unable to cope with the increased work of breathing. NIMV avoided Intensive Care Unit admission for 74% of the observed patients.

Acute Disease↗

[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors.

To date, there are no vasopressin (VP) agonists that exhibit a high affinity and selectivity for the VP V1b receptor with respect to the V1a, V2, and oxytocin receptors. In this study, we describe the synthesis and pharmacological properties of [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP). Binding experiments performed on various membrane preparations revealed that d[Cha(4)]AVP exhibits a nanomolar affinity for V1b receptors from various mammalian species (rat, bovine, human). It exhibits high V1b/V1a and V1b/oxytocin selectivity for rat, human, and bovine receptors. Furthermore, it exhibits high V1b/V2 specificity for both bovine and human vasopressin receptors. Functional studies performed on biological models that naturally express V1b receptors indicate that d[Cha4]AVP is an agonist. Like VP, it stimulated basal and corticotropin-releasing factor-stimulated ACTH secretion and basal catecholamine release from rat anterior pituitary and bovine chromaffin cells, respectively. In vivo experiments performed in rat revealed that d[Cha4]AVP was able to stimulate both ACTH and corticosterone secretion and exhibits negligible vasopressor activity. It retains about 30% of the antidiuretic activity of VP. This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies.

Adrenocorticotropic Hormone↗

Funding in vitro fertilization treatment for persistent subfertility: the pain and the politics.

OBJECTIVE: To consider the arguments for and against funding for in vitro fertilization (IVF) and to explore potential avenues for policy change. DESIGN: Narrative literature review, policy analysis. SETTING: University Department of Obstetrics and Gynecology. PATIENT(S): Sub-fertile women and men. INTERVENTION(S): Fertility treatments, in particular IVF. RESULT(S): The two main arguments used against funding for IVF are that [1] subfertility is a social, not a medical problem, and therefore its treatment is not medically indicated or necessary, and [2] the clinical effectiveness of IVF is unproven. These and other major arguments are critiqued. CONCLUSION(S): Dismissing IVF as medically unnecessary seems premature because medical necessity has not been operationally defined. Demonstrating IVF effectiveness through a randomized trial has not been done but is feasible: a multicenter trial is currently underway in Canada. Dealing with the concern that subfertility treatment challenges the role of women in society, as well as with questions of cost-effectiveness, are more difficult challenges that deserve further debate. The potential for unethical uses and broader social implications of IVF add to its dubious status and provide a convenient rationale for refusing to pay. However, none of these concerns is unique to IVF: many currently covered health services are susceptible to the same criticisms. For all services, judgments of eligibility for coverage should be consistent and transparent and should explicitly separate the issues of cost from other factors.

Canada↗

Doing better with "bad kids": explaining the policy-research gap with conduct disorder in Canada.

Conduct disorder (severe and persistent antisocial behaviour in children and youth) is an important community mental health problem in Canada and has been the focus of considerable recent public policy debate. Good research evidence is available on effective (and ineffective) interventions for conduct disorder. Paradoxically, however, relatively little of the research evidence is incorporated into policy decision-making. There is a policy-research gap. An example (Hamilton, Ontario) is used to illustrate this gap. The gap is then explained using a framework for health policy analysis that incorporates values, institutional structures, and information. Values and institutional structures greatly outweigh research evidence in influencing current Canadian policy-making for the problem of conduct disorder. Possibilities for improving the situation are suggested.

Canada↗

Artificial neural network based identification of environmental bacteria by gas-chromatographic and electrophoretic data.

Chemotaxonomic identification techniques are powerful tools for environmental micro-organisms, for which poor diagnostic schemes are available. Whole cellular fatty acid methyl esters (FAME) content is a stable bacterial profile, the analysis method is rapid, cheap, simple to perform and highly automated. Whole-cell protein is an even more powerful tool because it yields information at or below the species level. The description of new species and genera and subsequent continuous rearrangement provide large amounts of data, resulting in large databases. In order to set up suitable software tools to work on such large databases artificial neural network (ANN) based programs have been used to classify and identify marine bacteria at genus and species levels, starting from the fatty acid profiles and protein profiles respectively. We analysed 50 certified strains belonging to Halomonas, Marinomonas, Marinospirillum, Oceanospirillum and Pseudoalteromonas genera. Both supervised and unsupervised ANNs provide a correct classification of the marine strains analyzed. Moreover, a set of 73 marine fresh isolates were used as an example of identification using ANNs. We propose supervised and unsupervised ANNs as a reliable tool for classification of bacteria by means of their FAME and of whole-protein analyses and as a sound basis for a comprehensive artificial intelligence based system for polyphasic taxonomy.

Bacteria↗

Priority setting for new technologies in medicine: qualitative case study.

OBJECTIVE: To describe priority setting for new technologies in medicine. DESIGN: Qualitative study using case studies and grounded theory. SETTING: Two committees advising on priorities for new technologies in cancer and cardiac care in Ontario, Canada. PARTICIPANTS: The two committees and their 26 members. MAIN OUTCOME MEASURES: Accounts of priority setting decision making gathered by reviewing documents, interviewing members, and observing meetings. RESULTS: Six interrelated domains were identified for priority setting for new technologies in medicine: the institutions in which the decision are made, the people who make the decisions, the factors they consider, the reasons for the decisions, the process of decision making, and the appeals mechanism for challenging the decisions. CONCLUSION: These domains constitute a model of priority setting for new technologies in medicine. The next step will be to harmonise this description of how priority setting decisions are made with ethical accounts of how they should be made.

Costs and Cost Analysis↗

Acceleration of pubertal development following central blockade of the Y1 subtype of neuropeptide Y receptors.

Pubertal development results from the coordinate secretion of gonadotropin-releasing hormone (GnRH) by hypothalamic GnRH neurons. Central administration of neuropeptide Y (NPY) to prepubertal rats can indefinitely delay sexual maturation by inhibiting this GnRH secretion. The aim of the present study was to further investigate the physiological role of NPY in pubertal development, and to assess the potential involvement of its Y1 receptor subtype in this setting. The timing of pubertal development was determined in juvenile female rats receiving chronic i.c.v. infusion of a specific Y1 receptor antagonist (BIBP 3226), and compared with controls. Although treatment with BIBP 3226 did not affect the age at vaginal opening, animals receiving the Y1 antagonist experienced a quicker progression through puberty, corroborated by a significant increase in pituitary luteinizing hormone content. This effect of BIBP3226 on the gonadotrope axis occurred without apparent toxicity, but was accompanied by a transient decrease in body weight gain on the first day of treatment, suggesting an effect on appetite. Together, our results add to the evidence in favour of a role for NPY in the onset of puberty. They are entirely consistent with the proposed inhibition exerted by endogenous hypothalamic NPY before the onset of pubertal development. They also suggest that the Y1 subtype of NPY receptors is involved in this effect.

Aging↗

The many meanings of deinsuring a health service: the case of in vitro fertilization in Ontario.

There is currently much international interest in principles and processes for determining which services should qualify for health insurance packages. However, there has yet been little analysis of the implications of actual deinsurance decisions made by such priority-setting exercises. This paper reports experience from the case of in vitro fertilization (IVF) deinsurance in Ontario, Canada. The analysis addresses some of the more social aspects of financial incentives by characterizing funding structures as means of communicating complex policy objectives, rather than mechanistic reward-penalty systems. Deinsuring IVF was intended to support several policy goals, including: controlling public expenditures, restricting public coverage to 'medically necessary' services, applying evidence of effectiveness as a criterion for medical necessity and implementing part of a policy program to control new reproductive technologies. It may seem a modest step to remove one dubious service from public insurance coverage. Nevertheless, as interpreted by stakeholders, deinsurance of IVF may inadvertently promote the opposite of what policy makers intended. This case suggests that priority-setting decisions based on incomplete information, inconsistently applied principles and too little attention to health system dynamics (perhaps the norm in 'real-world' priority-setting) can have the perverse effect of undermining progress toward health reform goals of improved health, reduced expenditures and more rigorously evaluated services. The case of IVF in Ontario offers several lessons for other jurisdictions engaged in priority-setting and service deinsurance: (1) individual services interact with the rest of the system and cannot be removed without systemic effects, (2) inconsistent use of coverage principles can undermine legitimacy of both priority-setting principles and processes and (3) 'evidence-based' decisions can founder on differing stakeholder ideas about appropriate evidence and on the inconsistent message given by commercializing ineffective or unproven care.

Fertilization in Vitro↗

Towards a "good" death: end-of-life narratives constructed in an intensive care unit.

End-of-life decisions regarding the withdrawal and withholding of life supporting technology have become commonplace within intensive care units (ICUs). In this paper, we examine the dialogue between ICU team members and families regarding limitation of treatment as a therapeutic narrative--that is, as a story which frames therapeutic events as well as the critically ill patient's experience in a meaningful and psychologically comforting way for families and health care providers alike. The key themes of these end-of-life narratives are discussed, as well as the qualities that the stories share with other narratives of the same genre.

Attitude of Health Personnel↗

Comparative effects of levosulpiride and cisapride on gastric emptying and symptoms in patients with functional dyspepsia and gastroparesis.

BACKGROUND: The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well-established in patients with functional dyspepsia, but formal studies comparing different prokinetic drugs are lacking. AIM: To compare the effects of chronic oral administration of cisapride and levosulpiride in patients with functional dyspepsia and delayed gastric emptying. METHODS: In a double-blind crossover comparison, the effects of a 4-week administration of levosulpiride (25 mg t.d.s.) and cisapride (10 mg t.d.s.) on the gastric emptying rate and on symptoms were evaluated in 30 dyspeptic patients with functional gastroparesis. At the beginning of the study and after levosulpiride or cisapride treatment, the gastric emptying time of a standard meal was measured by 13C-octanoic acid breath test. Gastrointestinal symptom scores were also evaluated. RESULTS: The efficacy of levosulpiride was similar to that of cisapride in significantly shortening (P < 0.001) the t1/2 of gastric emptying. No significant differences were observed between the two treatments with regards to improvements in total symptom scores. However, levosulpiride was significantly more effective (P < 0.01) than cisapride in improving the impact of symptoms on the patients' every-day activities and in improving individual symptoms such as nausea, vomiting and early postprandial satiety. CONCLUSION: The efficacy of levosulpiride and cisapride in reducing gastric emptying times with no relevant side-effects is similar. The impact of symptoms on patients' everyday activities and the improvement of some symptoms such as nausea, vomiting and early satiety was more evident with levosulpiride than cisapride.

Activities of Daily Living↗

Pressure support ventilation in patients with acute lung injury.

OBJECTIVES: To assess the success rate of pressure support ventilation (PSV) in acute lung injury patients undergoing continuous positive pressure ventilation (CPPV), to study physiologic changes after the transition from CPPV to PSV, and to investigate differences between patients who succeed and patients who fail PSV according to predetermined criteria. DESIGN: Observational study. SETTING: General intensive care unit in a teaching hospital. SUBJECTS: We studied 48 patients having acute lung injury, as defined by a PaO2/F(IO2) <300 mm Hg and the presence of bilateral infiltrates on chest radiograph, and ventilated with CPPV. We included patients with PaO2 >80 mm Hg, at positive end-expiratory pressure of <15 cm H2O and with F(IO2) up to 1.0. INTERVENTIONS: After enrollment, PSV was instituted and patients were strictly monitored during the following 48 hrs. Subjects who met any of the predefined PSV failure criteria during this period were returned to CPPV (Group F). PSV was continued in the remaining patients (Group S). MEASUREMENTS AND MAIN RESULTS: Gas exchange, respiratory mechanics, and hemodynamics measurements were collected before switching from CPPV to PSV and were repeated at 24 hrs after beginning PSV, or immediately before return to CPPV in Group F patients. The physiologic deadspace volume to tidal volume ratio (V(D)/V(T)) was obtained by the Enghoff's equation from the measurement of the mixed expired CO2 fraction. PSV resulted in a significant PaCO2 decrease (49.2+/-10.9 mm Hg to 44.4+/-7.2 mm Hg) and significant increases in minute volume (V(E))(9.0+/-2.3 L/min to 12.0+/-4.0 L/min) and arterial blood pH (7.405+/-0.054 to 7.435+/-0.064), with stable oxygenation and hemodynamics. In patients who were hypercapnic (PaCO2 >50 mm Hg) during CPPV, the V(E) increase was higher than in normocapnic patients. In the latter patients, PaCO2 and pH did not change significantly going from CPPV to PSV. A total of 38 patients (79%) were allocated to Group S and the remaining 10 patients were included in Group F. In Group S, positive endexpiratory pressure of 9.4+/-2.9 cm H2O (range, 3-14 cm H2O) and a PSV level of 14.9+/-3.8 cm H2O (range, 9-22 cm H2O) were applied. In Group F, positive end-expiratory pressure of 8.9+/-3.1 cm H2O (range, 5-15 cm H2O) and a PSV level of 21.6+/-4.6 cm H2O (range, 16-31 cm H2O) were adopted. Compared with Group S, Group F had a longer duration of intubation (20.2+/-19.2 days vs. 9.2+/-13.5 days), a lower static compliance of the respiratory system (30.4+/-16.5 mL/cm H2O vs. 41.7+/-15.0 mL/cm H2O), and a higher V(D)/V(T) (0.70+/-0.09 vs. 0.52+/-0.10), but similar oxygenation and positive end-expiratory pressure. V(E) was higher in Group F during both CPPV and PSV. CONCLUSIONS: In a relatively high proportion of the investigated patients, PSV was successful. The institution of PSV led to no major changes in oxygenation or in hemodynamics. PSV was associated with increases in V(E) and respiratory frequency. In patients who had been hypercapnic during CPPV, PaCO2 decreased despite a compensated pH. Compared with PSV success patients, patients who failed PSV appeared to be sicker, as shown by the higher duration of respiratory support, increased ventilatory needs, and decreased respiratory system compliance, despite similar arterial oxygenation and positive end-expiratory pressure.

Acid-Base Equilibrium↗