Search PubMed⌕ Search

Biomedical subjects

E Ronchi

Publications and source records attributed to E Ronchi.

At least 19 recordsLinked to original sources

Genetic testing: policy issues for the new millennium.

The purpose of this article is to provide a brief overview of the policy considerations underlying the Organization for Economic Cooperation and Development (OECD) workshop, "Genetic Testing: Policy Issues for the New Millennium," which was organised and hosted by the governments of the United Kingdom (UK) and Austria in Vienna, 23-25 February 2000, with the support of the European Commission (EC). It reviews the various topics presented at the meeting and offers a brief summary of its main conclusions.

Biotechnology↗

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95% confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95% CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

Administration, Oral↗

Effects of vitamin E on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

A randomized controlled open trial studied the effect of vitamin E supplementation (300 mg/day) on clinic and 24-h ambulatory blood pressure (BP) in 142 treated hypertensive patients. After 12 weeks, clinic BP decreased whether or not patients were randomized to vitamin E. Ambulatory BP showed no change in systolic BP and a small decrease in diastolic BP (-1.6 mm Hg, 95% confidence intervals from -2.8 to -0.4 mm Hg), approaching statistical significance in comparison to the control group (P = .06). Vitamin E supplementation thus seems to have no clinically relevant effect on BP in hypertensive patients already under controlled treatment.

Antihypertensive Agents↗

[Rhabdomyolysis caused by improper intraoperative positioning. Clinical and medico-legal aspects].

The etiology, diagnosis, pathology and treatment of rhabdomyolysis due to intraoperative malpositioning and the medico-legal implications of physicians involved in the surgical treatment and anesthesia of the patient are described. According to the Italian law, the anesthesiologist is the only physician of the surgery-anesthesia team responsible for the patient's positioning. The anesthesiologist must assume primary responsibility for protecting the patient from iatrogenic injuries due to improper positioning, and/or inadequate preventive measures.

Adolescent↗

Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro.

Genistein significantly inhibited cell growth (IC50 around 10 microM) of MCF-7, MDAMB-231 and HBL-100 cell lines, but not of skin-derived fibroblasts and counteracted the growth-stimulatory effects exerted by estradiol and growth factors. It abolished the paracrine stimulation observed in MCF-7 cells in co-culture with MDAMB-231 or fibroblasts. Genistein-treated cells accumulated in the S and G2/M phases of the cell cycle and underwent apoptosis. Genistein decreased tyrosine phosphorylation induced upon treatment with transforming growth factor-alpha. Finally, genistein bound the estrogen receptor (ER) (relative affinity constant Kd = 4 nM), induced pS2 and cathepsin-D transcription and increased nuclear ER levels.

Antineoplastic Agents↗

Effects of photoperiod on brain corticosteroid receptors and the stress response in the golden hamster (Mesocricetus auratus).

Following exposure to short daylengths, in golden hamsters, changes in basal adrenal glucocorticoid secretion are associated with a significant increase in Type I receptor binding, and are preceded by alterations in the stress-induced release of glucocorticoids, which is one of the major modes of operation of the hypothalamo-pituitary-adrenocortical axis (HPA). These results lend support to the hypothesis that corticosteroid receptors, and in particular the Type I receptor subtype, play a central role in the regulation of circadian and circannual rhythms of the HPA.

Adrenalectomy↗

[Anesthesiologic incidents from esophageal intubation. Presentation of three cases and medico-legal evaluation].

Undiagnosed esophageal intubation is still prominently in anesthesia-related morbidity and mortality. Three cases of undiagnosed esophageal intubation taken into consideration for possible anesthesiologic malpractice are presented. A review of the international anesthetic-related morbidity and mortality statistics indicates that this misadventure remains a problem even among anesthesia personnel, a medical population specifically trained in such a procedure. It is not only the frequency of this misadventure but the potential catastrophic consequences for the patient that underline the importance of being able to recognise and correct an esophageal intubation. The reliability of commonly prescribed methods of assessing tracheal tube position is reviewed and the conclusion is drawn that continuous end-tidal carbon dioxide measurement during anesthesia is perhaps the most reliable means under all circumstances for determining proper tube position and should be employed routinely whenever possible.

Adult↗

Oral doxophylline in patients with chronic obstructive pulmonary disease.

Doxophylline, or 2-(7'-theophyllinemethyl)1,3-dioxolane, is a theophylline derivative which has shown interesting bronchodilating activity, and it appears to determine few adverse effects. The aim of the present investigation was to evaluate clinical therapeutic effects of the drug in the treatment of 2 groups of patients suffering from moderate to severe chronic obstructive pulmonary disease differing in acute response to the inhaled beta 2-agonist salbutamol and to compare changes of lung function tests to serum concentration of doxophylline. We studied 67 patients with chronic obstructive pulmonary disease (median age 63 years, 9 females and 58 males) who were all clinically stable at the time of the study. Patients were separated into 2 groups on the basis of their reaction to inhalation of 200 micrograms of salbutamol: those with an increased FEV1 of more than 20% from baseline value (group 1), and those with no increase (group 2). Doxophylline was administered orally at the dose of 400 mg 3 times daily. Serum levels of doxophylline were determined by high-pressure liquid chromatography. Spirometry and blood gas analysis were performed before and 10 days after treatment. Four patients stopped drug assumption because of side effects (3 for dyspepsia and 1 for anxiety). In group 1 (34 patients), a significant increase in SVC, FVC, FEV1, FEF 25-75% and PEFR was observed. In group 1 (29 patients), only PEFR significantly increased. No modifications in blood gas analysis were observed. The mean serum level of doxophylline was 14 micrograms/ml in group 1 and 9 micrograms/ml in group 2: the difference was statistically significant. The relation between serum levels of doxophylline and FVC showed an increase in the parameter up to the concentration of 12-13 micrograms/ml, after which a plateau phase was observed. On the basis of our data, doxophylline appears to have an interesting bronchodilating effect in patients responsive to the inhaled beta 2-agonist salbutamol. The lower limit of the therapeutic range seems to be 12-13 micrograms/ml. The upper limit of the therapeutic range was not determined because it was not possible to obtain serum samples when side effects occurred.

Administration, Oral↗

Expression of exogenous genes transferred into the avian limb in ovo.

We report on a simple method of direct gene transfer which allows the ectopic expression of proteins and the study of mesoderm-specific genes in the chick embryo. We microinjected into the avian embryonic limb several plasmids containing reporter genes under the control of various promoter sequences, including a minimal chicken muscle acetylcholine receptor alpha-subunit promoter [Klarsfeld, A., Daubas, A., Bourachot, B. and Changeux, J.P., Mol. Cell. Biol., 7 (1987) 951-955]. Gene expression is detectable for 3 days, is reproducible, is restricted to the site of injection, and correlates with the amount of DNA injected. Our observations indicate that it is possible to transfer and express genes in ectodermal and mesodermal cells of the chick limb by direct DNA injection and that the method can be used to analyze promoter sequences in vivo during specific windows of development.

Animals↗

Adverse events in the treatment of hypertensive patients.

We evaluated frequency and type of adverse events (AE) and measures adopted in outpatients attending a hospital hypertension unit in a two-part study: (1) a retrospective review of the charts of the 412 patients seen in 1991 with at least one follow-up visit and (2) a prospective study of the 491 patients seen in 1993 with at least one follow-up visit for whom physicians were asked to fill out an AE form. In 1991 18.6% of patients spontaneously reported an AE; those with an AE were older (p<0.001) than those without and included a greater proportion of females (p<0.002). This retrospective analysis of AE is reproducible as demonstrated by a blind review of 30 randomly selected charts undertaken by two independent observers (McNemar's test:p=ns). In 1993 AE were reported by 24.4% of patients who had more follow-up visits (p<0.001) and included a higher proportion of females (p=0.016) than the subgroup without AE. AE were different in the two studies (p<0.001), more specific and drug-related in 1993. AE were usually considered as mild or moderate (87.4%), the drugs most often involved were calcium antagonists and ACE-inhibitors and the measure adopted was switching to another substance (44%). The frequency of AE reporting varied widely between different physicians.

Journal Article↗

Promoter-specific regulation of gene expression by an exogenously added homedomain that promotes neurite growth.

pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoprotein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoproteins. Externally added pAntp specifically down-regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoprotein target sites.

Animals↗

Down-regulation of the Drosophila morphogen bicoid by the torso receptor-mediated signal transduction cascade.

Anterior body pattern in Drosophila is specified by the graded distribution of the bicoid protein (bcd), which activates subordinate genes in distinct anterior domains. Subsequently, transcription of these target genes is repressed at the anterior pole owing to the activity of the receptor tyrosine kinase torso (tor). We show that both activation by bcd and repression by tor can be reproduced by a minimal promoter containing only bcd-binding sites upstream of a naive transcriptional start site. Repression requires the D-raf kinase and is associated with phosphorylation of bcd protein. Repression does not require either tailless or huckebein, which were previously thought to constitute the sole zygotic output of the tor signaling system. Finally, addition of a heterologous transcriptional activation domain to bcd renders the protein insensitive to tor-mediated repression. We propose that phosphorylation resulting from the activity of the tor signal transduction cascade down-regulates transcriptional activation by the bcd morphogen.

Animals↗

Immunocytochemical study of GnRH and GnRH-associated peptide in male Syrian hamsters as a function of photoperiod and gonadal alterations.

Hypothalamic luteinizing-hormone-releasing hormone (GnRH) and gonadotropin-releasing-hormone-associated peptide (GAP) biosynthesis and storage were estimated by immunocytochemistry in male golden hamsters maintained in different photoperiods. Intact or castrated male hamsters with subcutaneously inserted testosterone implants were exposed to long-day (14:10) or short-day photoperiods (10:14) for 4-8 weeks. Exposure to short photoperiod for 4 weeks, an interval characterized by a suppression of gonadotropin secretion but not gonadal regression, was associated with an increase in the number of GnRH- and GAP-immunoreactive cells in the diagonal band of Broca/medial septum. Furthermore, morphometric analysis revealed that these animals displayed significantly more GnRH but not GAP immunoreactivity in the median eminence as opposed to hamsters exposed to long-day photoperiods. In additional studies, gonadally regressed hamsters exposed to short day lengths for 8 weeks had equal numbers of GnRH cells as did the long-day controls. These patterns suggest that reproductive quiescence in golden hamsters is not the result of depletions of neuronal GnRH stores available for secretion.

Animals↗

Steady state analysis of hypothalamic GnRH mRNA levels in male Syrian hamsters: influences of photoperiod and androgen.

An in situ hybridization assay, utilizing a free floating technique was used to estimate the steady state levels of hypothalamic luteinizing hormone-releasing hormone (GnRH) mRNA levels in the brains of male golden hamsters maintained in different photoperiods. In situ histochemistry was performed using a 32P-labelled 66-nucleotide long oligomer complementary to the sequence of the human GnRH mRNA coding region. The oligonucleotide hybridized specifically to mRNA encoding the GnRH precursor as suggested by the distribution of labelled neurons and as shown by an RNAse protection assay on septal and preoptic-hypothalamic mRNA from gonadally regressed hamsters. To test the hypothesis that short-day photoperiods reduce GnRH synthesis, intact male hamsters or castrated males bearing subcutaneously inserted testosterone implants were exposed to long-day (14 h light:10 h dark) or short-day (10 h light 14 h dark) photoperiods for 4 weeks. Exposure to short day lengths never caused a decrease in GnRH expressing neurons and actually was associated with an increase in the number of radiolabelled cells specifically in the diagonal band of Broca/medial septum in the gonadally intact group. The mean number of grains per labelled cell for the short day animals similarly was not reduced from that seen in long day animals. The results are consistent with previous studies on photoperiod and GnRH content in the same brain regions and support the notion that the suppression of the synthesis of GnRH does not accompany the low levels of LH secretion observed during the early stages of reproductive quiescence in this species.

Animals↗

[Absorption of short-acting insulin mixed with different slow-release formulations].

Several authors point to a different action of soluble insulin when mixed with a lente formulation containing either protamine or zinc. We evaluated glucose and insulin profiles in 17 type I diabetics, every one of whom was given what was considered the optimal amount of insulin twenty minutes before a standard evening meal. The patients were studied on two occasions, one week apart. According to a randomized sequence, those who received first the protamine-soluble mixture, took the Zn-soluble combination after one week and vice-versa. At the same time, we determined anti-insulin antibodies in order to rule out any different immunological interference, in the two moments of the study. Our results confirm that protamine-insulin given together with regular shows a serum insulin peak which is earlier and higher than that obtained with the corresponding mixture of Zn-insulin and regular (ANOVA: F = 5, 96; p = 0.02); blood glucose levels were lower with the former regimen, even though the difference did not reach statistical significance. Our conclusion is that Zn-containing insulin partly inactivates regular insulin when administered in the same syringe, and this may have an impact on the long-term treatment of the diabetic patient.

Adult↗

Expression of P-glycoprotein in breast cancer tissue and in vitro resistance to doxorubicin and vincristine.

Expression of P-glycoprotein was evaluated by C219 monoclonal antibody immunoblots in 34 previously untreated and 14 pretreated breast cancers and in benign breast lesions or histologically normal breast glands. P-glycoprotein was not detectable in the few cases of normal or benign tissue. P-glycoprotein was expressed in the 170 kD areas of 29% (10/34) of untreated and 64% (9/14) of previously treated tumours (P = 0.02). In treated tumours, high intensity expression was observed more frequently than in untreated breast cancer (40% vs. 9%). Moreover, there was a significant association between P-glycoprotein expression and in vitro resistance to doxorubicin and vincristine. Simultaneous resistance was observed in all of the P-glycoprotein positive and in only 56% of the P-glycoprotein negative tissues (P less than 0.01). Some aspects of the typical multidrug resistant phenotype, such as P-glycoprotein expression and simultaneous resistance to doxorubicin and vincristine, could be detected in small subsets of breast cancer patients. No relation between P-glycoprotein expression and the type of previous clinical treatment was observed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Compliance and long-term prognosis in hypertensive patients. Case series in a specialized hospital outpatient service].

In this study of ambulatory patients who had their first visit at the hypertension Unit of the Ospedale San Carlo Borromeo in Milan during the years 1979-1983, we report some data regarding compliance and long-term prognosis of mild hypertension. In these 5 years, 445 mild hypertensives (mean DBP: 103.3 +/- 13.2 mmHg) came to our facilities at least once: of these, 57 (12.9%) have been in constant touch with the outpatient clinic until today; 310 (69.6%) have been lost to follow-up after less than 1 year; 78 (17.5%) had an irregular pattern of attendance with a mean length of follow-up of 3.49 +/- 1.8 years. These data indicate a less than ideal compliance especially for patients who were older, smokers, not married and with no previous pharmacological treatment at the first visit. Index of morbidity and mortality for all causes and for cardiovascular disease and blood pressure control were better, although without reaching statistical significance, in the 57 patients with the best compliance. Altogether our data point to a reevaluation of the approach to the problem of mild hypertension through specialised hospital facilities.

Adult↗