PubMed Health⌕ Search

Biomedical subjects

R Giorgi

Publications and source records attributed to R Giorgi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluating the prognosis of multiple, severely traumatized children in the intensive care unit.

OBJECTIVE: To assess the Pediatric Risk of Mortality (PRISM) score and to identify other prognosis factors in severe, multiple trauma in children. DESIGN: Retrospective study over a 9-year period. SETTING: A Pediatric Intensive Care Unit (PICU) in a University Hospital. PATIENTS AND PARTICIPANTS: One hundred and thirty-three traumatized children, 8.6 years (8 months-16 years), were reviewed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Pediatric Trauma Score (PTS), Injury Severity Score (ISS), New ISS (NISS), Glasgow Coma Scale (GCS) score, and PRISM were calculated. The areas under the Receiver Operating Characteristic (ROC Az) curves, were compared. Univariate and multivariate analyses were performed. The mortality rate was 25.6%. PRISM performed well for discrimination between survivors and non-survivors. Az PRISM 0.9387 (0.029) was not different from Az GCS score 0.9451 (0.027) (P=0.568), but was significantly different from Az ISS 0.756 (0.052) (P<0.001), Az NISS 0.7606 (0.051) (P<0.001), and Az PTS 0.8244 (0.047) (P=0.016). Death was significantly associated with head trauma (P=0.014), PRISM >35, PTS <5, GCS <7, and ISS or NISS >32 (P<0.00001). PRISM >35 (P=0.001) and GCS <7 (P=0.003) were independent risk factors of death. CONCLUSIONS: PRISM is a reliable tool for evaluating the prognosis of multiple, severely traumatized children. Its relative simplicity and the fact that it is extremely widespread as a general prognosis score in PICUs represent other arguments for its use. Due to the leading influence of head trauma on mortality, GCS, a score even simpler than PRISM, showed identical accuracy regarding survival prediction.

Adolescent↗
PubMed2001

Tolerance to the antinociceptive effect of Crotalus durissus terrificus snake venom in mice is mediated by pharmacodynamic mechanisms.

Crotalus durissus terrificus venom exerts central and peripheral antinociceptive effect mediated by opioid receptors. The present work investigated the tolerance to the antinociceptive effect of the venom and characterised the mechanisms involved in this phenomenon. The hot plate test, applied in mice, was used for pain threshold determination. The venom (200 microg/kg) was administered by oral route, daily, for 14 days, and the nociceptive test was applied before and on days 1, 7 and 14 of the treatment. Prolonged treatment with venom lead to the development of tolerance to the antinociceptive effect. Tolerant animals exhibited increased sodium pentobarbital-induced sleeping time, although total hepatic microsomal cytochrome P450 was not altered. The antinociceptive effect of a single dose of venom (200 microg/kg) is mediated by kappa opioid receptors. Mice long-term-treated with venom showed cross-tolerance to U-TRANS, an agonist of kappa-opioid receptor, but not to morphine or DAMGO, two mu-opioid receptor agonists. Prolonged administration of venom did not cause symptoms of abstinence syndrome. These data indicate that prolonged treatment with C. durissus terrificus venom induces tolerance to the antinociceptive effect and that pharmacodynamic mechanisms are involved in the genesis of this phenomenon.

Analgesics↗
PubMed2001

Tubular lesions and tubular cell adhesion molecules for the prognosis of lupus nephritis.

BACKGROUND: To assess the prognostic value of tubular lesions and cell adhesion molecules' expression, a retrospective study with immunohistochemistry was performed on 152 patients presenting lupus nephritis from January 1985 to December 1999. METHODS: The following clinical parameters were recorded: age, sex, race, time of systemic lupus erythematosus (SLE) diagnosis, time of the biopsy, proteinuria, creatininemia, and renal function at the end of follow-up. All biopsies were re-evaluated according to a tubular grading, an inflammatory grading, the percentage of sclerosed glomeruli, the percentage of crescents, and the current WHO classification. Immunohistochemistry was performed with anti-CD40, anti-CD44, and anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibodies. RESULTS: Patients were 136 women (89.5%) and 16 men with a mean age of 31.2 years +/- 12.8 at the time of biopsy. The mean follow-up period was 94.3 months +/- 64.1. Eighty-eight biopsies (58%) showed various degrees of tubular atrophy. Males (P = 0.001) and tubular grading (P = 0.0001) were linked with renal survival in univariate and multivariate analysis. CD40 (P = 0.01) and ICAM-1 (P = 0.001) tubular expressions were linked with renal survival. ICAM-1 tubular expression provided additional information for the prognosis of the patients with biopsies showing tubular atrophy (P = 0.005) or not (P = 0.05). CONCLUSIONS: Our study shows that tubular lesions are good indicator of lupus nephritis outcome. Furthermore, tubular expression of cell adhesion molecules like ICAM-1 and CD40 also serves to predict the outcome.

Adult↗
PubMed2001

Pax-2 expression in adult renal tumors.

To assess the expression of the homeogene Pax-2 in adult renal cell carcinomas, we did a retrospective immunohistochemical analysis of 56 frozen tumor samples representing all major histologic subtypes of renal tumors. There were 33 conventional renal cell carcinomas (58.9%), 12 papillary renal cell carcinomas (21.4%), 4 chromophobe cell renal carcinomas, 4 urothelial cell renal carcinomas, and 3 oncocytomas. Forty-five tumors (62.5%) were localized, and 21 tumors had extrarenal involvement. Eight patients (14%) had metastatic disease at the end of the follow-up. We searched for relationships between Pax-2 expression and nuclear grading, TNM staging, Ki-67 proliferation index, expression of transforming growth factor-beta1 (TGF-beta 1), an in vitro down-regulator of Pax-2 expression, and finally cytogenetic abnormalities. All histologic subtypes expressed Pax-2 protein, except urothelial renal carcinomas. The highest expression was in papillary renal cell carcinomas. In this subtype, all tumors and 83.3% +/- 12.3% of tumor cells were immunoreactive for Pax-2. All but 2 conventional renal cell carcinomas expressed Pax-2, but with 26.3% +/- 29.6% of immunoreactive cells (P <.001). Pax-2 expression was not correlated with nuclear grading (P =.6), tumor size (P =.3), and TGF-beta 1 expression (P =.1). Nevertheless, Pax-2 expression correlated with the Ki-67 proliferation index only for the conventional histologic subtype (P =.03). In this histologic subtype, Pax-2 expression was higher in patients with metastatic disease than in those without (P =.02). Pax-2 expression was not associated with specific cytogenetic abnormalities like trisomy 7 (P =.1), 3p deletion (P =.5), and hyperdiploidy (P =.2). TGF-beta 1 expression, positive in 33 tumors (59%), was not correlated with either Pax-2 expression (P =.1) or current prognostic factors such as nuclear grading (P =.2). Interestingly, we also observed an expression of TGF-beta RI and TGF-beta RII in the tumors with high nuclear grading (P =.005). We conclude that Pax-2 protein is expressed in all major histologic subtypes of renal cell carcinomas. The pattern of expression differs between these subtypes. Pax-2 expression in conventional renal cell carcinomas is correlated with the proliferation index and is significantly higher in patients with metastatic disease. HUM PATHOL 32:282-287.

Adenoma, Oxyphilic↗
PubMed2001

Relative survival: comparison of regressive models and advice for the user.

BACKGROUND: Relative survival is a method of analysis of failure-time data used to estimate the net survival. Cancer registries frequently use this method. The main regressive models are the Hakulinen and Tenkanen model, and the Esteve et al. model, which are easily used in practice thanks to their specific software (SURV and RELSURV, respectively). An assessment of the behaviour of the models is made, with the aim of giving advice for users of lifetime data in practice. METHODS: Simulations were done by respecting, then violating, the basic hypothesis supporting the theoretical foundation of these two proportional hazard models (independence of the death and censor process, proportionality of risks). For each simulation, 100 files of either 100, 1,000, or 10,000 individuals were generated to assess the behaviour of the model. RESULTS: Moderate censor rates, with or without proportionality assumption, lead to the use of the Hakulinen and Tenkanen model, especially for studies with little information. Non-proportionality of risks in the Hakulinen and Tenkanen model could be tested and analysed. If assumptions underlying the models are respected, the Esteve et al. model seems to be more precise. DISCUSSION: The choice of a model in practice depends on its performance, and on the user's knowledge of statistics and computer science. Non-proportionality of risks is common in cancer registries. In theory, non-proportionality of risks could be taken into account for both relative survival models but, for the moment, it is feasible in routine only for the Hakulinen and Tenkanen model. Characteristics of the software should also be taken into account for routine relative survival analyses.

Data Interpretation, Statistical↗
PubMed2001

Elaboration and formalization of current scientific knowledge of risks and preventive measures illustrated by colorectal cancer.

OBJECTIVES: Present the method used to elaborate and formalize current scientific knowledge to provide physicians with tools available on the Internet, that enable them to evaluate individual patient risk, give personalized preventive recommendations or early screening measures. METHODS: The approach suggested in this article is in line with medical procedures based on levels of evidence (Evidence-based Medicine). A cyclical process for developing recommendations allows us to quickly incorporate current scientific information. At each phase, the analysis is reevaluated by experts in the field collaborating on the project. The information is formalized through the use of levels of evidence and grades of recommendations. GLIF model is used to implement recommendations for clinical practice guidelines. RESULTS: The most current scientific evidence incorporated in a cyclical process includes several steps: critical analysis according to the Evidence-based Medicine method; identification of predictive factors; setting-up risk levels; identification of prevention measures; elaboration of personalized recommendation. The information technology implementation of the clinical practice guideline enables physicians to quickly obtain personalized information for their patients. Cases of colorectal prevention illustrate our approach. CONCLUSIONS: Integration of current scientific knowledge is an important process. The delay between the moment new information arrives and the moment the practitioner applies it, is thus reduced.

Colorectal Neoplasms↗
PubMed2001

Guideline development: focus on breast cancer screening in the EsPeR project.

We describe in this paper, the implementation of a clinical practice guideline focused on breast cancer screening. Our aim in conceiving such a computerized guideline was first to help general practitioners in appreciating the risks their female patients might develop breast cancer and secondly to suggest them the screening measures adapted to each particular case. This implementation enables us to present our general methodology to elaborated and promulgate guidelines within the EsPeR project. This methodology aims at providing guidelines based on knowledge validated according to the EBM principles, that can be used in real time and updated according to current knowledge.

Algorithms↗
PubMed2001

An adaptive medical e-learning environment: the MEDIDACTE project.

Most e-learning systems offer the same tools and resource materials to students who are different in terms of motivations, training backgrounds, technical skills and learning objectives. Adaptive systems development is a challenge intended to improve the efficiency of these systems. This communication presents the design and implementation of an adaptive medical e-learning environment. The authors describe the MEDIDACTE architecture developed in three levels namely, the educational resource, educational project and user level. Current MEDIDACTE implementation and integration in Marseille Medical University curriculum are presented.

Computer Literacy↗
PubMed2000

delta-opioid receptors and nitric oxide mediate the analgesic effect of Crotalus durissus terrificus snake venom.

The antinociceptive effect of Crotalus durissus terrificus venom was investigated in a model of inflammatory hyperalgesia induced by carrageenin. The rat paw pressure test was applied before and 3 h after the intraplantar (i.pl.) injection of carrageenin. The venom administered per os before and 1 or 2 h after carrageenin blocked hyperalgesia. When carrageenin was injected in both hind paws and naloxone into one hind paw, antinociception was abolished only in the paw injected with naloxone. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) and nor-binaltorphimine, antagonists of micro- and kappa-opioid receptors, respectively, did not alter the effect of the venom. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI 174,864), an antagonist of delta-opioid receptors, antagonised this effect. Prolonged administration of the venom did not induce tolerance to this antinociceptive effect. N(G)-methyl-L-arginine (L-NMMA) and methylene blue, inhibitors of nitric oxide synthase and soluble guanylate cyclase, respectively, injected i.pl., antagonised antinociception. These data indicate that both delta-opioid receptors and nitric oxide participate in the mediation of the peripheral antinociceptive effect of C. durissus terrificus venom.

Analgesics, Non-Narcotic↗
PubMed2000

The use of the personalized estimate of death probabilities for medical decision making.

Data coming from the French national statistics on the cause of deaths are used to calculate the probabilities of death from pathologies. These probabilities are calculated according to age, sex, and place of residence of the patient to "personalize" the estimate. This individual prediction of the risk of death is proposed for pathologies for which the feasibility and the utility of prevention measures had been demonstrated. Relative risks of death according to the socioprofessional category, which are coming from the scientific literature, are used to adjust the probabilities of death as a function of the patient socioprofessional category. The aim of this work is to guide a scientist toward a prevention strategy according to the age and characteristics of patient. The use of computers by the scientists will make possible the diffusion of such tool of prediction to improve a personalized prevention.

Cause of Death↗
PubMed2000

[From knowledge to clinical practice: the introduction of evidence-based medicine].

INTRODUCTION: The paper presents the new paradigm for medical practice which has been emerging for a decade: evidence-based medicine. CURRENT KNOWLEDGE AND KEY POINTS: The paradigm proposes new skills for the physicians, de-emphasizing intuition and empiricism in medical practice, and proposes the intensive use of medical literature for the medical practice. FUTURE PROSPECTS AND PROJECTS: The article presents the main characteristics of the approach which is raising new important questions about the evolution of medical practice and the validity of the paradigm.

Delivery of Health Care↗
PubMed2000

Tubular lesions determine prognosis of IgA nephropathy.

To assess the prognostic value of histological classification for renal outcome, we did a multivariate analysis of 194 patients with immunoglobulin A (IgA) nephropathy between 1985 and 1995. We also evaluated semiquantitative scales of tubular lesions and vessel lesions. At the time of the biopsy, 65 patients (33.5%) had chronic renal failure. At the end of the follow-up, 33 patients (17%) required hemodialysis. The mean age of the patients was 37.8 +/-18.9 years with predominance of men (sex-ratio: 3.12). Patients were followed-up for a mean of 43.2 +/- 37.2 months. Univariate analysis showed that hypertension (P < 10(-4)), nephrotic syndrome (P = 0.01), and crescents (P = 0.02) were significant in predicting renal failure, unlike subendothelial topography of IgA deposits (P = 0.05) and proteinuria (P = 0.05). Hematuria was a protective factor (P = 0.03). Multivariate analysis showed that tubular grade 2 (relative risk [RR], 5.5) and tubular grade 3 (RR = 28.8) were the best factors to predict chronic renal failure. The histological classification of Haas was significant in the univariate analysis, but not in the multivariate analysis. Tubular grading predicted renal outcome better than did the other histological parameters.

Adolescent↗
PubMed1998

Antinociceptive effect of the calcium-binding protein MRP-14 and the role played by neutrophils on the control of inflammatory pain.

Macrophages secrete a variety of chemical mediators that play a central role in the pathophysiology of inflammatory pain. Therefore, the activation or deactivation of these cells in an inflammatory focus could modulate the intensity of the algogenic response. Based on these premises and on our previous demonstration that the calcium-binding protein MRP-14, highly expressed in neutrophils, deactivates activated macrophages in vitro, we decided to investigate the role of MRP-14 and of neutrophils in the control of inflammatory pain in mice. Our results show that this protein is endowed with antinociceptive activity. When tested in the writhing model it was able to inhibit pain response but did not change the behavior of the animals in the hot plate test. This observation indicates that MRP-14 down-regulates inflammatory but not central pain. Using a model of acute neutrophilic peritonitis induced by glycogen, a close correlation between neutrophil migration and antinociception was detected. Surgical adrenalectomy demonstrated that the antinociceptive response induced by glycogen was not due to endogenous liberation of glucocorticoids. The treatment of animals either with a monoclonal antibody anti-MRP-14 or a monoclonal antibody that depletes the animals of neutrophils reverts the antinociceptive response observed in the glycogen-induced peritonitis. These data define the calcium-binding protein MRP-14 as a novel mediator for the control of inflammatory pain and consequently discloses an anti-inflammatory role for the neutrophil.

Abdomen↗
PubMed1998

The antinociceptive effect of Crotalus durissus terrificus snake venom is mainly due to a supraspinally integrated response.

The antinociceptive effect of Crotalus durissus terrificus snake venom, previously demonstrated in the hot-plate test, was investigated in mice using the tail-flick model. The venom, administered by the intraperitoneal, subcutaneous or oral route, did not modify the basal latency time to the noxious stimulus and the association of the venom with morphine did not alter the opioid analgesic effect of this drug. These data indicate that the antinociceptive effect of the venom is mainly due to a supraspinally integrated response.

Animals↗
PubMed1998

Mutational analysis of N-RAS and GAP-related domain of the neurofibromatosis type 1 gene in chronic myelogenous leukemia.

RAS mutations can be detected in a variable number of patients with myeloproliferative disorders such as myelodysplastic syndromes and acute myeloid leukemia, but are rare events in chronic myelogenous leukemia in chronic phase. However, there is good evidence supporting the involvement of RAS signalling pathway in CML and this could be due to alterations in RAS activity regulatory proteins. The neurofibromatosis (NF1) gene down-regulates the RAS signal transduction pathway through the inhibitory function of its GAP-related domain (GRD) on RAS protein. The loss or alteration of neurofibromin (the NF1 protein) may produce a disfunction similar to point mutations in the RAS gene resulting in the permanent stimulation of the RAS signal transduction pathway. Mutations involving the GRD region of the NF1 gene (GRD-NF1) have been described in a variety of tumors such as colon carcinoma and astrocytoma. Germline mutations and deletions in the NF1 gene, as seen in neurofibromatosis type 1, are also associated with certain myeloid disorders. In the present work, we sought to identify mutations in the codons 12/13 and 61 of RAS gene and in the Lys-1423 codon of GRD-NF1, which are well known hot spots in these genes, in a group of 36 adults and ten children with chronic myelogenous leukemia in chronic phase and blast crisis. Using the PCR-SSCP and the allele-specific restriction assay (ASRA) techniques, we were not able to observe any RAS or NF1 detectable mutation. These findings suggest that RAS and GRD-NF1 mutations are not involved either in chronic phase or in the progression to blast crisis in chronic myelogenous leukemia in adults and children.

Adult↗
PubMed1995

4-Diazinyl- and 4-pyridinylimidazoles: potent angiotensin II antagonists. A study of their activity and computational characterization.

A series of N-[biphenylyl(tetrazolyl)methyl]-2-butylimidazoles containing variously substituted diazine or pyridine moieties either as their free bases or N-oxide derivatives attached to the 4-position of the imidazole ring was synthesized and tested for interaction with the AT1 receptors of rat adrenal cortex membranes (receptor binding assay). Some compounds were then chosen for further evaluation in vivo in the A II-induced pressor response in conscious normotensive rats. The most potent in the AT1 binding assay were found to be compounds in which the diazine or pyridine ring nitrogen is adjacent to the point of attachment between the two heteroaromatic rings such as 2-butyl-4-(3,6-dimethylpyrazin-2-yl)-1-[[2'-(1H-tetrazol-5-y l)-biphenyl-4- yl]methyl]-1H-imidazole (3b) or 2-butyl-4-[5-(methoxycarbonyl)pyrid-2-yl]-1-[[2'-(1H-tetrazol++ +-5- yl)biphenyl-4-yl]methyl]-1H-imidazole (6c). The binding affinities and oral activities of the pyridine N-oxide imidazoles in which a stabilizing group ortho to the pyridine ring nitrogen is present were markedly improved as in 2-butyl-4-[(3-methoxycarbonyl)-6-methyl-N-oxopyridin-2-yl]-1-[[2'- (1H- tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole 31b. Molecular modeling studies were carried out to determine the molecular electrostatic potential values of related model systems and to correlate their receptor interaction energies with the observed activities of our compounds.

Administration, Oral↗
PubMed1994

Absolute configuration and biological activity of mequitamium iodide enantiomers.

The enantiomers of 1-methyl-3-(10H-phenothiazine-10-ylmethyl)-1-azoniabicyclo[2 ,2,2]octane iodide (1) were prepared by chiral chromatographic resolution of the precursor mequitazine (2). The (+)-(S)-enantiomer 1b is 10-fold more potent than (-)-(R)-enantiomer 1a as a histamine antagonist, while the two enantiomers show the same antimuscarinic activity in vitro. The absolute configuration of the more active dextrorotatory isomer has been determined by X-ray analysis. Conformational analysis and molecular modeling suggest that the (+)-(S)-enantiomer can adopt a conformation similar to that attributed to the receptor binding conformers of classical antihistamines.

Acetylcholine↗