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Biomedical subjects

A Fanelli

Publications and source records attributed to A Fanelli.

At least 19 recordsLinked to original sources

Monitored anesthesia care.

According to the American Society of Anesthe-siologists (ASA), a monitored anesthesia care (MAC) is a planned procedure during which the patient undergoes local anesthesia together with sedation and analgesia. Actually MAC is the first choice in 10-30% of all the surgical procedures. The 3 fundamental elements and purposes of a conscious sedation during a MAC are: a safe sedation, the control of the patient anxiety and the pain control. The patients undergoing conscious sedation are able to answer to orders appropriately and to protect airways. Last but not least, another purpose of any MAC is to get the patient appropriately satisfied, allowing him to get his discharge as faster as possible. There are many surgical procedures which can be performed using a MAC. The patient consciousness evaluation is of extreme importance during the surgical procedure performed with MAC: to this purpose the clinical and electroencephalographic evaluations such as Bispectral Index are very useful. MAC can be obtained with the association of fast half-life drugs or drugs getting a clinical effect which can vary according to the surgical requirements, using an infusion regiment. Apart from the pharmacological choice, this procedure can be performed with patient controlled sedation techniques or with continued intravenous infusion or with target controlled infusion.

Analgesia↗

Erythropoietin-dependent anaemia: a possible complication of diabetic neuropathy.

We report the case of a 52-year-old woman with long-term type 1 diabetes mellitus, complicated with proliferative retinopathy, autonomic neuropathy and microalbuminuria and moderate renal failure. A normochromic, normocytic are generative anaemia had been diagnosed for three years. Clinical and biological investigations for the aetiology of anaemia remained normal or negative. Anaemia was associated with a concentration of erythropoietin (EPO) in the normal range, but inappropriately low regarding anaemia. Treatment with recombinant EPO induced a rapid increase in haemoglobin level and improved the patient's quality of life. The role of diabetic neuropathy in the genesis of anaemia, in conjunction with a modest renal impairment is discussed.

Albuminuria↗

[Prospective follow-up study of renal function in type 2 diabetes].

Type 2 diabetes mellitus is the main cause of increase in patients suffering from end-stage renal failure in France. We performed an observational study of the change in renal function of type 2 diabetic patients, attending our diabetology clinic. Clinical and biological data were regularly entered in an informatic database (Pénélope, Poitiers University Hospital). We prospectively followed 351 type 2 diabetic patients (age at diagnosis: 40 to 75 years), for 32 months (extremes: 1-120). Renal function was graded in 4 stages according to plasma creatinine and urinary albumin excretion (UAE) determined by nephelometry on random urinary sample: absent (UAE < 20 mg/L et creatinine < 150 mumol/L), incipiens (UAE 20 to 200 mg/L and creatinine < 150 mumol/L), established (UAE = 200 mg/L et creatinine < 150 mumol/L) advanced (creatinine = 150 mumol/L). Glycated haemoglobin (HbA1c) was determined by HPLC. Systolic/Diastolic Blood Pressure (SBP/DBP) was measured with a mercury sphygmomanometer. We defined renal events as the change from one stage of nephropathy to a higher one. A total of 351 type 2 diabetic subjects were studied: 194 men/157 women mean age 63 +/- 11 years, mean diabetes duration 10 +/- 9 yr. At baseline, 206 patients had no nephropathy, 98 incipient nephropathy, 28 established nephropathy and 19-advanced nephropathy. Baseline stage of nephropathy was related to SBP (p < 0.0001), DBP (p = 0.0002), diabetes duration (p = 0.0064) but not HbA1c (p = 0.2182) or sex (p = 0.4794). Among those 332 subjects without baseline advanced nephropathy, 134 progressed in nephropathy. Progression of nephropathy was not related to the presence of hypertension (SBP/DBP > or = 160/95 mmHg) (log-rank = 0.22; p = 0.6377). Conversely, patients with a poor glycaemic control (HbA1c > or = 10%) had a worse renal-event free survival (log-rank = 4.89; p = 0.0269). Glycaemic control is a risk factor for the progression in nephropathy of type 2 diabetic patients.

Adult↗

Glucagon-like peptide (GLP)-1 and leptin concentrations in obese patients with Type 2 diabetes mellitus.

AIMS: To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemic and isoinsulinaemic conditions, between obese patients with and without Type 2 diabetes mellitus. METHODS: Ten male obese (body mass index (BMI) > 30 kg/m2) patients with Type 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, GLP-1(7-36)amide and GLP-1(7-37) concentrations were measured 0, 30, 60, and 90 min after a 50-g oral glucose load administered 90 min after the beginning of a euglycaemic hyperinsulinaemic clamp. RESULTS: GLP-1(7-36)amide concentrations before the glucose load were significantly lower in diabetic patients than in controls (median (quartiles): 50.5 (44.7-53.2) vs. 128.7(100-172.5) pg/ml; P < 0.01), while no difference was observed in baseline GLP-1(7-37). In non-diabetic subjects, GLP-1(7-36)amide and GLP-1(7-37) concentrations increased significantly after the oral glucose load, while no glucose-induced increase in GLP-1 concentration was observed in diabetic patients. GLP-1(7-36)amide at 30, 60, and 90 min, and GLP-1(7-37) at 30 min, of the glucose challenge, were significantly lower in diabetic patients. Leptin concentrations were not significantly different in diabetic patients when compared to non-diabetic subjects, and they did not change after the oral glucose load. DISCUSSION: Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.

Blood Glucose↗

Psychology of the scientist: LXXXII. Coverage of classical conditioning in textbooks in the psychology of learning, 1952-1995.

Objective information was obtained from 89 textbooks in the psychology of learning published from 1952 through 1995 to answer questions about their coverage of classical conditioning. We found (a) that classical conditioning consistently received less coverage than instrumental and operant conditioning, (b) that the distinction of classical and instrumental conditioning has become established as a textbook-construction device, (c) that use of the classical-instrumental distinction by textbook authors has "hardened" after a period of "fluidity" in the 1970s, (d) that the currency of references in the basic classical (as well as instrumental) conditioning chapters diminished from 1952 to 1995. Findings are discussed in regard to the possibility that, as a class, and in comparison to other textbooks, the textbooks of the psychology of learning fall short of fulfilling some of their recognized roles.

Animals↗

The c-erbB-2 oncogene amplification by competitive PCR in aneuploid cell clones flow sorted from breast cancer samples.

The amplification of c-erbB-2 oncogene has been reported to have clinical relevance as a prognostic index in breast cancer. However, controversies still remain about its interpretation, mainly due to the inaccuracy of methods used for this purpose and to the unpredictable variability of the ratio between cancer and normal cells. Accurate quantitative assay, combined with strategies for selection or enrichment of tumor cell populations, could shed a new light on the relationships between molecular alterations and their clinical relevance. In this study, amplification of c-erbB-2 was measured by competitive PCR in 21 aneuploid breast cancers using a multiple DNA competitor both in whole homogenized cancer cells and in aneuploid enriched clones obtained after flow cytometry cell sorting. Most breast cancers (10/12) carrying c-erbB-2 oncogene amplification showed a significant increase in copy number in sorted aneuploid clones, and 2/9 apparently not amplified in basal samples were found to be amplified after being sorted for the aneuploid population. A general concordance between amplification and c-erbB-2 overexpression was found. The mean degree of amplification in sorted aneuploid clones is increased in breast cancers with the highest levels of c-erbB-2 protein overexpression. These data indicate that in breast cancers the amplification of c-erbB-2 oncogene is mainly associated with aneuploid cells.

Aneuploidy↗

Ciona intestinalis nuclear receptor 1: a member of steroid/thyroid hormone receptor family.

Nuclear hormone receptors comprise a large family of zinc finger transcription factors, some with hydrophobic ligands, such as thyroid hormone, vitamin D, steroids, etc., and others for which no ligand has been found. Thyroid hormone receptors (TRs) generally are considered to be confined to the vertebrata that possess a thyroid gland. Tunicates represent the most primitive of the chordates, and there are data supporting a role for thyroid hormone in their metamorphosis, but no data are available on TRs in this genus; hence, we have studied Ciona intestinalis. Screening of a Ciona library with the DNA binding domain of Xenopus laevis TR (xTR) resulted in the isolation of a nuclear hormone receptor, C. intestinalis nuclear receptor 1 (CiNR1). CiNR1 is similar to TRs of more evolved species with a conserved DNA binding domain whereas the ligand binding domain shows poor homology to vertebrate sequences. The C-terminal part of CiNR1 spans approximately 200 amino acids more than other TRs, lacks the AF2 transactivation domain, and is not able to bind triiodothyronine. Phylogenetically, CiNR1 appears to be close to the common ancestral gene of TRs. Expression of CiNR1 was limited to the developing embryo and the larval stage, which suggests a role during development and metamorphosis. In transfection experiments, CiNR1 down-regulated basal transcription of a reporter gene driven by the TR palindrome responsive element. When CiNR1 was cotransfected with chicken TRalpha, it attenuated the normal thyroid hormone response in a dominant negative fashion. This attenuation required the C-terminal portion of the molecule.

Amino Acid Sequence↗

Reticulocytes and reticulated platelets: simultaneous measurement in whole blood by flow cytometry.

Reticulated platelets are a fraction of newly released circulating elements characterized by a residual amount of RNA. It has been suggested that the reticulated platelet count, providing an estimate of thrombopoiesis in the same way as erythrocyte reticulocyte count is a measure of erythropoiesis, may be useful in the study of thrombocytopenic disorders. Reticulated red cells and platelets can be analyzed by flow cytometry using specific stains for nucleic acids such as Thiazole Orange and Auramine-O. The aim of our work was to perform the simultaneous evaluation of reticulated elements in whole blood using a standard flow cytometer and to correlate the results obtained with a dedicated cytometer. A group of 14 patients with abnormal absolute reticulocyte counts (range 1.1-11%) and a group of 41 patients showing a platelet discrimination error when analyzed with a dedicated flow cytometer (Sysmex R1000) were enrolled. Linear amplification of both scatter and fluorescence was used to perform reticulocyte count. A gate was set on platelet dimensions, and logarithmic amplification of scatter and fluorescence was used to count reticulated platelets. A good correlation was obtained both for results of reticulocyte count (r2 = 0.9825) and for reticulated platelets (r2 = 0.8717) between our method and those using dedicated instruments. These data show that reticulated platelet count may be easily introduced in clinical laboratories that routinely perform reticulocyte count by flow cytometry.

Benzophenoneidum↗

Possible pathogenetic role of activated platelets in the primary antiphospholipid syndrome involving the central nervous system.

Neurological disorders occurring in the primary antiphospholipid syndrome (neuro-PAPS) have not yet been completely understood. Platelet activation has been suggested to play a crucial role in the pathogenesis of hemostatic disorders in the antiphospholipid syndrome, but no association with neuro-PAPS has been investigated so far. Therefore, we investigated 16 patients with PAPS by flow cytometry in the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoprotein CD62. In addition, the relationship among activated platelets and anticardiolipin antibodies (aCL) was evaluated. Compared to normal subjects CD62 was found significantly increased in these patients. Furthermore, a significantly increased percentage of CD62-positive platelets was found in the neuro-PAPS group (nine patients) compared to the non-neuro-PAPS patients (seven subjects). On the contrary, no significant difference was found between the two groups with regard to aCL IgG and platelet number. Furthermore, within the neuro-PAPS group, no difference was evidenced, in the CD62-positive platelet percentage, between the four subjects with thrombocytopenia and the five with the normal blood platelet count. Similarly, neuro-PAPS subjects with previous peripheral arterial and/or venous thrombosis did not show a significantly more elevated level of CD62-positive platelets. Finally, a linear correlation was found between the aCL IgG level and the CD62-positive platelet percentage in all the patients and, more significantly, in the neuro-PAPS group, but not within the non-neuro-PAPS patients. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, aCL, and neurological disease that patients affected by PAPS might undergo.

Adult↗

Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment epithelium.

The retinal pigment epithelium transports lactate between two tissue compartments, the interphotoreceptor matrix and the choriocapillaris. In this report we describe a 2.45-kb cDNA isolated from a chick cDNA RPE library that encodes a membrane protein found only in RPE cells. The deduced protein has 542 amino acids with twelve putative membrane spanning domains. The cDNA has been designated MCT3 based on its 45% identity in amino acid sequence and structural similarity with the monocarboxylate transporters MCT1 and MCT2. Stable transfectants (pCl-neo/MCT3), made in a rat thyroid epithelial cell line (FRTL-5), express MCT3 RNA. Transfectants had enhanced pyruvate uptake (used as a measure of lactate uptake) which was proton-dependent and inhibited by alpha-cyano-4-hydroxycinnamate. In summary, MCT3's unique expression in RPE cells, multiple potential phosphorylation sites, and basolateral distribution suggest that MCT3 may regulate lactate levels in the interphotoreceptor space.

Amino Acid Sequence↗

Flow cytometric detection of circulating activated platelets in primary antiphospholipid syndrome. Correlation with thrombocytopenia and anticardiolipin antibodies.

Platelet activation has been suggested to play a crucial role in the pathogenesis of haemostatic disorders in antiphospholipid syndrome (APS). In 16 patients with primary APS (PAPS) we investigated by flow cytometry the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoproteins CD62 and CD63. In addition, the relationships among activated platelets, thrombocytopenia, antiphospholipid antibodies (aPL) and platelet associated IgG (PalgG) were evaluated. Compared to normal subjects CD62, but not CD63 expression, was found significantly increased in patients. All thrombocytopenic subjects showed a percentage of CD62 expressing platelets above the cut off. In thrombocytopenics a significantly increased percentage of CD62 and higher levels of aCL IgG were found compared to PAPS patients with normal platelet count. No correlation was found between activated platelets and both lupus anticoagulant antibodies and PalgG. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, thrombocytopenia and aPL levels.

Adult↗

Flow cytometric measurement of DNA content in human solid tumors: a comparison with cytogenetics.

The aims of this study were: (1) to test the accuracy of flow cytometery (FC) in the measurement of DNA content in human solid tumors, (2) to correlate the FC DNA-index (DI) with the chromosome modal number (CMN) provided by cytogenetic analysis (CG), and (3) to investigate the most frequent pitfalls in FC histograms classification. FC and CG analyses were performed in parallel on 113 samples of human solid tumors of different origin. FC provided an evaluable histogram in 110 out of 113 cases (97%), whereas a successful CG culture was obtained in 79 out of 113 samples (72%). In the 79 cases evaluable by both FC and CG, a concordant ploidy status was found in 66 cases (84%) (47 diploid and 19 aneuploid) (P < 0.001, chi-square test). In the 19 concordant aneuploid tumors a close correlation between the CMN and the DI was found (y = 0.019 x + 0.151; r = 0.860). Concerning the 13 discordant cases, 11 (85%) were classified as aneuploid by FC and as diploid by CG, while 2 cases (15%) were CG aneuploid (1 near-diploid and 1 tetraploid) and FC diploid. The current study suggests that FC is a reliable method for the measurement of tumor DNA content of the studied solid tumors. Special attention should be paid to the improvement of DNA histograms quality, in order to reduce the difficulties in the detection of near-diploid and near-tetraploid cell populations. Multiple sampling should be warranted whenever possible.

Aneuploidy↗

Inhibition of iodide transport in rat thyroid cells using N-substituted anthranilic acid derivatives.

The purpose of this study was to test the effects of chloride channel blockers on iodide uptake in thyroid cells, in the hope of eventually using these blockers to identify and isolate a putative iodide transporter. The chloride channel blockers used in this report are derivatives of N-substituted anthranilic acid and were synthesized using published procedures. For these studies FRTL-5 cells, a line of continuous-growing rat thyroid cells, were used as a model system to study effects on iodide transport. In these cells, there are at least two ways for transmembrane iodide movements, a sodium-dependent influx step and a proposed channel that normally mediates iodide efflux. Two derivatives studied decreased iodide accumulation in FRTL-5 cells, but were found also to lower intracellular pH and ATP levels. To simplify interpretation of the effect of the drugs on iodide transport, we extended the studies using plasma membrane vesicles made from pig thyroid. Iodide entry in these vesicles depended on a sodium gradient and was independent of ATP levels. Iodide transport in plasma membrane vesicles and FRTL-5 cells was measured at 30 sec when the uptake was nearly linear and therefore likely to reflect iodide entry. The uptake was measured using three concentrations of iodide and three of drug. Kinetic analysis of the data described a competitive inhibition by the drugs with a Ki of approximately 250 microM. In summary, N-substituted anthranilic acid derivatives reversibly inhibit iodide entry in FRTL-5 cells and pig plasma membrane vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Setting up and statistical evaluation of a new haemoglobin assay.

A new method for the determination of haemoglobin concentration in human whole blood has been devised. The assay takes advantage of the lysis of erythrocytes that occurs when blood penetrates the pores of a microporous membrane by a strong capillary effect. The released haemoglobin reacts with the reagents previously dried on the membrane, diffuses through the pores of the membrane and produces a uniform coloured spot whose reflectance at 556 nm can be evaluated at the side to that of application of the sample. In the experimental conditions used by authors, a linear relationship was obtained when the reciprocal reflectance was plotted against the haemoglobin concentration. Data obtained by the reflectometric method were compared with reference values on the same samples from centralized laboratories. Statistical analysis gave a correlation coefficient of 0.985 and only 4% of all haemoglobin determinations were outside the 95% confidence interval. No interference was observed by haematocrit, erythrocyte count, mean corpuscular volume or mean corpuscular haemoglobin concentration and leukocyte count. This method proved to be useful for rapid, accurate and precise assay of total haemoglobin on both capillary and venous blood.

Blood Cell Count↗

Histamine induced changes in breathing pattern may precede bronchoconstriction in selected patients with bronchial asthma.

BACKGROUND: In asthmatic patients methacholine or histamine challenge may result in more rapid and shallow breathing. Bronchoconstriction can also be associated with changes in the pattern of breathing. However, few studies, particularly in patients with asthma, have investigated the possibility that changes in the pattern of breathing may precede the onset of bronchoconstriction. METHODS: Eight subjects were selected from 34 consecutive asthmatic patients who had previously exhibited a significant increase in respiratory frequency (Rf) and decrease in tidal volume (VT) accompanying a 20% or greater fall in FEV1 during a histamine bronchial provocation test. These patients also had bronchial hyperresponsiveness (histamine PC20FEV1 0.1-0.25 mg/ml). VT, Rf, and the ratio of VT to Rf were evaluated breath by breath under control conditions and two minutes after inhalation of either saline or each of a series of progressively increasing concentrations of histamine. In each subject the coefficient of variation (CV) for each breathing pattern variable was calculated under control conditions and at each histamine concentration over at least 30-40 breaths. For FEV1, VT and Rf step by step coefficients of variation were averaged and the mean (2SD) CV was considered to represent a threshold value in each patient. RESULTS: Histamine challenge resulted in increased Rf and Rf/VT, and decreased VT and FEV1. In all but one subject change in Rf and Rf/VT beyond the threshold value preceded change in FEV1 beyond the threshold value. The threshold concentrations of histamine for Rf and Rf/VT did not correlate with the threshold value for FEV1. CONCLUSIONS: In selected asthmatic patients a change in breathing pattern occurs prior to a change in FEV1. These results suggest that narrowing of the airways, in terms of decrease in FEV1, does not play a major part in the initial change in the pattern of breathing. This may be caused by direct stimulation of vagal airway receptors.

Adult↗