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R Manfredini

Publications and source records attributed to R Manfredini.

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

A functionally active RARalpha nuclear receptor is expressed in retinoic acid non responsive early myeloblastic cell lines.

Although all-trans retinoic acid (ATRA) can restore the differentiation capacity of leukemic promyelocytes, early leukemic myeloblasts are conversely not responsive to ATRA induced granulocytic differentiation. To assess whether this resistance to ATRA is related to an impaired function of the Retinoic Acid Receptor alpha (RARalpha), we performed an analysis of RARalpha expression and transactivation activity, in several myeloid leukemic cell lines, representative of different types of spontaneous acute myeloid leukemias. Our results indicate that a functionally active RARalpha nuclear receptor is expressed in all the analyzed cell lines, regardless of their differentiation capacity following exposure to ATRA. The observation that ATRA treatment is able to induce the expression of retinoic acid target genes, in late- but not in early-myeloblastic leukemic cells, raises the possibility that the differentiation block of these cells is achieved through a chromatin mediated mechanism. Acetylation is apparently not involved in this process, since the histone deacetylase inhibitor trichostatin A, is not able to restore the differentiation capacity of early leukemic myeloblasts. Further investigation is needed to clarify whether myeloid transcription factors, distinct to RARalpha, play a role in the resistance of these cells to ATRA treatment.

Alkaline Phosphatase↗
PubMed2001

Day-night variation in aggressive behavior among psychiatric inpatients.

Self-directed aggressive behaviors of human beings show a 24h pattern. The aim of this study was to evaluate if violence of psychiatric inpatients against one another and hospital staff varies over the 24h. The clock time occurrence of 334 episodes of assault behaviors by 119 psychiatric inpatients (78 males and 41 females, mean age 34.8+/-11.3 years) committed during a 5-year span in the psychiatric unit of the university-based hospital of Ferrara, Italy, was evaluated. The clock time of each event was categorized by hour during the 24h and into one of four 6h intervals for analysis of temporal variation by cosinor and chi2 tests, respectively. A significant 24h variation, characterized by an early afternoon peak, was detected irrespective of gender and number (single vs. repeated) of episodes committed. Changes during the 24h in ward activity, patient contact, and endogenous circadian rhythms are likely to contribute to the observed 24h pattern, although further study is needed to confirm our findings and to define causal factors.

Adult↗
PubMed2001

Circadian differences in the individual sensitivity to opiate overdose.

OBJECTIVE: The aim of the present study was to test whether circadian differences in the response to opiates exist in humans and, if so, whether they are synchronized with the well-known circadian variations in overdose frequency. DESIGN: Daily variations in opiate overdose frequency, total amount of naloxone necessary to treat the comatose state, and frequency of hospitalization were examined in pure, nonlethal, consecutive cases of opiate (presumably intravenous heroin) overdoses. Furthermore, daily variations in the frequency of lethal overdoses were examined in all cases observed during the same period. SETTING: An 8-yr prospective, observational study in the city and suburban area of Ferrara, Italy. PATIENTS: A total of 518 consecutive cases of nonlethal opiate overdoses in 327 different patients, plus 110 consecutive cases of lethal opiate overdoses with precise or presumptive time of death. RESULTS: Analysis of the circadian distribution of nonlethal overdoses showed a significant peak in the afternoon to early evening. Analysis of the distribution of the hourly average amount of naloxone used to rescue patients from coma showed an opposite circadian variation, with a significant peak in the early morning. The hospitalization risk was also significantly higher from 3:00 to 8:59 am. However, in a subset of representative cases, plasma morphine concentrations did not change significantly in different hours of the day. Analysis of circadian distribution of lethal overdoses showed a significant peak in the evening hours. The death risk (calculated as the percentage of lethal events in the total number of intoxications within a given time frame) was significantly higher from 3:00 to 8:59 am. CONCLUSION: The present data provide evidence for the existence of circadian variations in the individual sensitivity to opiate overdose.

Adult↗
PubMed2001

Chronobiology of non fatal pulmonary thromboembolism.

BACKGROUND: It as been demonstrated that acute myocardial infarction, sudden cardiac death, stroke, and fatal pulmonary embolism show an increased onset rate during certain periods of the day, week, or year. According to some authors, the highest risk appears to occur in the morning, on weekends and during winter. This paper, therefore, intends to examine whether a circadian, weekly, or annual rhythm in the incidence rate of deep vein thrombosis (DVT) and non-fatal pulmonary embolism (PE) in ageing patients does exists. METHODS: A survey was conducted into 212 patients affected by DVT and PE, admitted to the Second Medicine Institute of Padua, Italy, over a period of two solar years. Thromboses were diagnosed via echo-Doppler examination of the legs and pulmonary embolism via perfusive and ventilatory scintiphotographs. RESULTS: In the overall sample, a circadian variation was found, both for deep vein thrombosis (peak at 12:26 hrs, p=0.001), and pulmonary embolism (peak at 10:26 hrs, p=0.001). A weekly, rhythmic recurrence was also found for the two complaints, with a peak on Saturdays, while no significant annual rhythmic recurrence was found. There was, however, a tendency towards an increase during the winter and summer months. CONCLUSIONS: The results may have important clinical applications, both in prevention and in the timing of drug dosage.

Chronobiology Phenomena↗
PubMed2001

[Epistaxis and circadian rhythm].

It is known that many physiological variables show a rhythmic variability along a time span, e.g.: day, week, month or year. It is possible that the temporal overlapping of a constellation of factors may act as favouring and/or triggering factors for the onset of several acute diseases. Among these, epistaxis shows a circadian variability too. Such pattern, characterised by a prevalent peak in the morning and a secondary one in the evening, strictly resembles that of arterial blood pressure. The lack of differences between the temporal pattern of hypertensive and normotensive subjects suggests that the physiological pattern of blood pressure, and not strictly a condition of hypertension, may play a favouring role in certain hours of the day, probably together other local factors.

Circadian Rhythm↗
PubMed2000

Renal infarction: an uncommon mimic presenting with flank pain.

A 39-year-old woman arrived to the emergency department complaining of a constant, progressive, left flank pain, with no beneficial effect from spasmolytic and nonsteroidal antiinflammatory drugs. Two years before, she suffered another episode of right flank pain and stranguria, but instrumental examinations (ultrasonography, urography) remained negative. Besides a mild tenderness in the left flank, physical examination was normal. Blood chemistry panel showed leukocytosis (17.2 x 10(3) mL, neutrophils 82.8%) and a slight increase of serum lactate dehydrogenase (LDH) (543 U/L versus 230 to 460 U/L). Urinanalysis showed a slight hemoglobinuria (0.5 mg/dL), and sediment contained some red cells and leukocytes. Diagnostic examinations (ultrasonography, computed tomography) showed a left renal nonhomogeneous space-occupying lesion, orientative for renal malignancy. She was transferred to the urology department and operated. Both intraoperatory and histological diagnosis was ischemic infarction and, after exclusion of all possible underlying causes, final diagnosis was idiopathic renal infarction. Diagnostic procedures and literature reports are discussed.

Adult↗
PubMed2000

Circadian variation in onset of acute cardiogenic pulmonary edema is independent of patients' features and underlying pathophysiological causes.

BACKGROUND: The present study aimed to confirm the existence of a circadian pattern in the onset of acute pulmonary edema (APE) and to verify whether sex, age, preexisting diseases, and clinical causes determining the event may influence it. SUBJECTS AND METHODS: The study considered all consecutive cases of APE observed at the St. Anna General Hospital of Ferrara, Italy, during a 7-year period from January 1, 1992, to December 31, 1998. The sample population was divided into subgroups by sex, age (<75 and > or =75 years), presence or absence of diabetes and hypertension, clinical causes determining the event (i.e., acute myocardial infarction (AMI), pulmonary embolism, arrhythmias). The most important associated or concomitant diseases were also considered (i.e., coronary heart disease and angina, previous myocardial infarction, chronic cardiac failure, dilatative cardiopathy, chronic atrial fibrillation, valvular disease, chronic obstructive pulmonary disease, chronic cor pulmonale, malignancy, chronic renal failure). Time of symptom onset of each event was recorded accurately, then tabulated into 24 increments of 1h (e.g., 06:00 to 06:59 was reported as 6 A.M.). For statistical chronobiological analysis, partial Fourier series were used. RESULTS: During the 7-year period, 1321 consecutive cases of APE in 1014 different subjects were observed. The majority of events occurred at night, and statistical analysis showed a 24h rhythmicity both in the total sample population and in all considered subgroups, with the only exception being patients with pulmonary embolism and arrhythmias, for which the small number of cases made the study of rhythms in APE impossible. CONCLUSIONS: The nighttime preference in the occurrence of APE appears to be quite independent of all demographic features or underlying pathophysiological causes.

Acute Disease↗
PubMed2000

Platelet alpha2-adrenoceptor alterations in patients with essential hypertension are normalized after treatment with doxazosin but not propranolol.

OBJECTIVE: Marked alterations have been demonstrated to occur in the platelet alpha2-adrenoceptors of patients with essential hypertension. The purpose of this study was to determine whether antihypertensive treatment with alpha-adrenergic blocker doxazosin or beta-adrenergic blocker propranolol can affect the affinity and the density of platelet alpha2-adrenoceptors in such patients. SUBJECTS AND METHODS: In two groups of 22 previously untreated, essential hypertensive patients, the mean affinity (Kd) and density (B(max)) of platelet alpha2-adrenoceptors were studied by [3H]-UK 14304 binding assays; the first assays were performed before any medication was begun, the second were performed after treatment for up to 13 weeks with doxazosin or propranolol. A third group of 22 healthy normotensive volunteers matched by age, sex and body mass index was used as control. RESULTS: Blood pressure did not differ significantly in the two hypertensive groups, and treatment with the two drugs resulted in closely similar, normal blood pressure levels. Kd and B(max) values were significantly higher in the two hypertensive groups than in controls. After treatment with propranolol the binding parameters did not change significantly, whereas after treatment with doxazosin Kd and B(max) returned to normotensive values. CONCLUSIONS: In previously untreated, essential hypertensive patients platelet alpha2-adrenoceptors have a lower affinity but a higher density than in normotensive subjects. Despite similar effects on blood pressure, the treatment with the alpha-adrenergic blocker doxazosin is followed by restoration of normal findings in the binding assays of platelet alpha2-adrenoceptors whereas the treatment with the beta-adrenergic blocker propranolol does not alter the Kd and B(max) values.

Adrenergic alpha-Agonists↗
PubMed1999

Induction of a functional vitamin D receptor in all-trans-retinoic acid-induced monocytic differentiation of M2-type leukemic blast cells.

Different types of acute myeloid leukemia blast cells were induced to differentiate in vitro with all-trans-retinoic acid (ATRA) and vitamin D3 (VD). M0/M1 leukemic cells are not sensitive to differentiating agents, whereas M3 leukemic cells are induced to undergo granulocytic differentiation after ATRA treatment but are not sensitive to VD. M2 leukemic blast cells behave differently because they undergo monocytic differentiation with both the differentiation inducers. To gain some insight into the maturation of M2-type leukemic cells, we studied the molecular mechanisms underlying monocytic differentiation induced by ATRA and VD in spontaneous M2 blast cells as well as in Kasumi-1 cells (an acute myeloid leukemia M2-type cell line). Our results indicate that ATRA as well as VD efficiently increases the nuclear abundance of VD receptor (VDR) and promotes monocytic differentiation. VDR is functionally active in ATRA-treated Kasumi-1 cells because it efficiently heterodimerizes with retinoid X receptor, binds to a DR3-type vitamin D-responsive element, and activates the transcription of a vitamin D-responsive element-regulated reporter gene. Consistent with these findings, VD-responsive genes are induced by ATRA treatment of Kasumi-1 cells, suggesting that the genetic program underlying monocytic differentiation is activated. The molecular mechanism by which ATRA increases the nuclear abundance of a functional VDR is still unknown, but our data clearly indicate that the M2 leukemic cell context is only permissive of monocytic differentiation.

Acute Disease↗