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Biomedical subjects

R Manfredini

Publications and source records attributed to R Manfredini.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Combination of transesophageal atrial pacing and echo-dipyridamole test in the diagnosis of coronary disease in patients with suspected angina pectoris and negative exercise test].

BACKGROUND: Echo-dipyridamole test is an useful tool for non-invasive demonstration of inducible myocardial ischemia in patients with coronary artery disease, its sensitivity being consistently higher as compared with classic exercise stress testing. However, in patients with single vessel who often perform a normal or borderline stress test, even the sensibility of echo-dipyridamole test is comparatively reduced. METHODS: In 19 patients with clinically suspected angina (effort-related in 4, at rest in 8, mixed in 7) and normal exercise stress test, standard echo-dipyridamole test was performed. Thereafter, rapid atrial pacing, a procedure associated with a sharp increase of myocardial oxygen consumption, was performed by means of a transoesophageal catheter during the proceeding 5 min and during 4 min of repeated dipyridamole 0.56 mg/kg infusion. RESULTS: Standard echo-dipyridamole test induced ventricular wall motion abnormalities in 3 patients (one with borderline exercise stress test), whereas repeated pacing-sensitized procedure obtained wall motion abnormalities (apical, septal and lateral) in the same and in 4 additional patients. Coronary angiography demonstrated > 70% stenosis in 8/19 patients (single vessel disease in 5), 7 of whom had been correctly recognized by pacing-dipyridamole test; therefore, sensitivity of the latter as compared with standard dipyridamole test was 87% and 37% respectively. The anatomic correlation of induced wall motion abnormalities with coronary arterial stenosis was demonstrated in all cases. Specificity was 100% with both methods. CONCLUSIONS: Although limited by its restricted patient population, this study suggests that atrial pacing, performed via transoesophageal catheter, can significantly improve the positive predictive value of echo-dipyridamole test in coronary artery disease. By means of this simple procedure, the possibility of non invasively diagnosing even single vessel stenosis in patients with inconclusive exercise stress testing can be significantly improved.

Adult↗
PubMed1994

Sudden death in diabetic subjects: evidence for a peculiar circadian variation in occurrence.

Anatomo-physiopathological and chronobiological features of 59 diabetic subjects out of 610 non hospitalized individuals observed for sudden death (SD) in an Emergency Room, over an 8-year period, were studied. Mean age and anatomopathological causes of SD were not different between diabetic (DMs) and non-diabetic subjects (NDs). However the frequency of DMs was higher among subjects who died from circulatory failure death (CFD), rather than from arrhythmic death (AD). Diabetics presented a prevalent peak incidence of SD in the afternoon-late evening; whereas in NDs two peaks were present, respectively in the morning and in the afternoon. According to anatomo-physiopathological causes, DMs presented a higher incidence of acute myocardial infarction (AMI) and CFD between 21:01 and 24:00, whereas in NDs the prevalent peak of AMI was observed in the early afternoon (13:01 to 16:00). Moreover, in DMs SD from acute myocardial failure prevalently occurred in the early afternoon (13:01 to 16:00), whereas in NDs it was uniformly distributed throughout the day. The present study seems to indicate that different anatomo-physiopathological causes of SD may present specific temporal patterns in diabetics.

Circadian Rhythm↗
PubMed1994

Anatomoclinical and chronobiological aspects of sudden death in elderly subjects.

Anatomoclinical and chronobiological aspects of sudden death (SD) of 671 subjects observed at the Emergency Room of Ferrara Hospital from January 1983 to December 1991 were prospectively investigated. 3 groups stratified by age were considered: group A with age < 65 years (no. = 251, 37.4%), group B with age between 65 and 74 years (no. = 210, 31.3%), and group C with age > or = 75 years (no. = 210, 31.3%). SD was classified on the basis of either anatomopathological (i.e.: acute myocardial infarction, acute myocardial failure, intracerebral hemorrhage, rupture of aortic aneurysm, pulmonary embolism), and clinical findings (i.e.: arrhythmic death and circulatory failure death). Patients were grouped into six 4-hour periods according to the time of onset of symptoms, and circadian distribution was tested for uniformity by a chi 2 test for goodness of fit. The analysis found in group C an increased frequency of SD due to pulmonary embolism and rupture of aortic aneurysm, and an increment of males/females ratio in deaths from cardiac causes. In group C the mean age of SD, in particular from acute myocardial infarction, pulmonary embolism or arrhythmic death proved higher in females compared to males. Only for group B was a significant circadian periodicity found for SD from acute myocardial infarction and arrhythmic death, with a peak in the morning.

Age Factors↗
PubMed1994

Antiapoptotic effect of c-fes protooncogene during granulocytic differentiation.

The c-fes protooncogene is expressed at high levels in the terminal stages of granulocytic differentiation. Its product, p92c-fes, exhibits a tyrosine-kinase activity and is involved in the cellular response to GM-CSF, but its role is not yet clarified. To study this problem, the c-fes protooncogene expression has been inhibited in HL60 cells and in fresh leukemic blast cells of Acute Promyelocytic Leukemia (APL) induced to differentiate with All-Trans-Retinoic Acid (ATRA). Inhibition of c-fes function was obtained by treatment of the cells with a specific antisense oligomer complementary to the 5' region of the c-fes mRNA. It was observed that the cells, rather then differentiate to granulocytes, underwent premature cell death showing the morphological and molecular characteristics of apoptosis. Superimposable results are obtained on blast cells from APL. It is possible to conclude that the loss of cell viability that occurs during the in vitro differentiation of myeloid cells, after the complete inhibition of c-fes expression and treatment with ATRA, is due to activation of programmed cell death rather than an accelerated differentiation. Our data suggest that the c-fes product is essential for the survival of myeloid cells during differentiation.

Apoptosis↗
PubMed1993

Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation.

The c-fes protooncogene is expressed at high levels in the terminal stages of granulocytic differentiation, but so far no definite function has been attributed to the product of this oncogene. To tackle this problem, the c-fes protooncogene expression has been inhibited in HL60 cells, and fresh leukemic promyelocytes of acute promyelocytic leukemia have been induced to differentiate with retinoic acid (RA) and dimethylsulfoxide (DMSO). Inhibition was obtained by incubating the cells with a specific c-fes antisense oligodeoxynucleotide. It was observed that the cells, rather than differentiating, underwent premature cell death showing the morphological and molecular characteristics of apoptosis. This process was inhibited by granulocyte and granulocyte/macrophage colony-stimulating factor, but not by interleukin 3 (IL-3), IL-6, or stem cell factor. Our present results demonstrate that the loss of cell viability that occurs during the in vitro differentiation of myeloid cells, after the complete inhibition of the c-fes gene product and treatment with RA-DMSO, is due to activation of programmed cell death. It is concluded that a possible role of the c-fes gene product is to exert an antiapoptotic effect during granulocytic differentiation.

Apoptosis↗
PubMed1993

Chronobiological aspects of acute cerebrovascular diseases.

The study was aimed at further investigating the circadian and circannual patterns of stroke onset. Study design and type of participants: 977 strokes (475 in men and 502 in women) concerning 926 subjects (457 men and 469 women) admitted to Ferrara Hospital in two calendar years (1990-1991), were prospectively investigated. The strokes were classified as based on cerebral infarction (CI), transient ischemic attack (TIA) and cerebral hemorrhage (CH: subarachnoid and intracerebral hemorrhage). Two statistical models of analysis were used. The assessment of circadian and circannual periodicity was performed utilizing the single cosinor method. A separate analysis was performed after distribution of events into 6-hour intervals, and chi-square test for fit was applied to the number of observed versus expected cases. The majority of strokes occurred in the morning between 7 a.m. and noon (35% of cases) and the hypothesis of a uniform distribution of the time onset was rejected on the basis of the chi-square for all subtypes of stroke. A circadian rhythm was found for CI and TIA with acrophase at the 11.56 and 12.41 respectively. Also a circannual periodicity was found for CI with a prevalent peak in October. The spectral analysis detected a circadian cycle for CH having a period of 4 h, and a circannual cycle for TIA with a period of 4 months. This study confirms that stroke is a high-chrono-risk disease, with specific circadian and circannual rhythms. This is very important for a better understanding and control of the underlying factors and in terms of prevention.

Acute Disease↗
PubMed1993

Expression of interleukins 1, 3, 6, stem cell factor and their receptors in acute leukemia blast cells and in normal peripheral lymphocytes and monocytes.

Reverse transcriptase-polymerase chain reaction amplification (RT-PCR) and Southern blot analysis were used to evaluate ligand and receptor expression of interleukin 1 alpha (IL-1 alpha), interleukin 3 (IL-3), interleukin 6 (IL-6) and stem cell factor (SCF) in peripheral blood lymphocytes and monocytes and in several acute leukemia blast cell populations. Resting peripheral lymphocytes and monocytes expressed both ligand and receptor of the four cytokines at considerable levels. The leukemic blast cells of the M1-M4 phenotypes are characterized by almost complete lack of expression of IL-1 alpha, IL-3 and IL-6 and the constant and usually high expression of SCF. On the other hand, these myeloid blast cells express generally high levels of the four cytokine receptors. The data suggest that the regulation of the expression of IL-1 alpha, IL-3 and IL-6, at least in our limited number of leukemic cell populations studied, is independent of that of SCF. The results indicate that, at least in most of the leukemic myeloid blasts cells, the expression of SCF and its receptor, the c-kit oncogene, may permit an autocrine regulation of cell cycling.

Acute Disease↗
PubMed1993

Sudden death may show a circadian time of risk depending on its anatomo-clinical causes and age.

The aim of this study was to determine whether the time of occurrence of sudden death exhibits a circadian rhythm depending on its different anatomoclinical causes. A longitudinal prospective investigation of 610 nonhospitalized subjects who died suddenly in the Emergency Room of Ferrara Hospital between January 1983 and December 1990 was conducted. All subjects underwent autopsy. Sudden death was classified on the basis of the following pathological causes; acute myocardial infarction, acute myocardial failure, intracerebral hemorrhage, rupture of aortic aneurysm, pulmonary embolism, and clinical causes, i.e., arrhythmia and circulatory failure. The investigated cases were stratified into 2 groups according to age; Group A = age < 70 years (n = 301, 49.3%), and Group B = age > or = to 70 (n = 309, 51.7%). The assessment of circadian rhythmicity was performed utilizing the single cosinor method. The results by cosinor analysis found a circadian rhythmicity for cases of sudden death (peak at 14.04, n = 610, p = 0.036), and in particular for females (peak at 13.12, n = 200, p = 0.004). Spectral analysis detected a statistical ultradian cycle in males having an 8-hour period (p = 0.015). A statistically significant circadian rhythm was found for cases of sudden death due to acute myocardial infarction (peak at 15.28, n = 330, p = 0.013), pulmonary embolism (peak at 11.46, n = 56, p = 0.003) and arrhythmia (peak at 13.08, n = 291, p = 0.04). In Group A no significant circadian rhythm was found, whereas in Group B a significant rhythmicity was found for sudden death from cardiac causes at 13.32 (n = 249, p = 0.015), from myocardial infarction at 15.02 (n = 154, p = 0.018) and from arrhythmia at 13.07 (n = 122, p = 0.014). Different circadian patterns of onset of sudden death may be shown in various subgroups of patients, due not only to different pathophysiologic mechanisms but also to anatomo-clinical aspects.

Age Factors↗
PubMed1993

Overexpression of c-kit in a leukemic cell population carrying a trisomy 4 and its relationship with the proliferative capacity.

The expression of c-kit and its ligand, the stem cell factor (SCF), was studied in five cases of acute myeloid leukemia. One of these had a trisomy of chromosome 4, where the c-kit oncogene is located. In this case, the c-kit oncogene was overexpressed, but matched by a low expression of its ligand, SCF. The molecular evaluation of the growth rate by c-myc and the histone H3 expression indicated that the growth fraction of this cell population was very low. In one of the other leukemic cell populations studied, characterized by a low expression of c-kit and an elevated expression of the SCF, the growth fraction was also very low. Our results suggest that at least for some receptor oncogenes, the simple overexpression cannot be taken as an indication that the oncogene is involved in the deregulation of cell proliferation.

Base Sequence↗
PubMed1993

Chronoepidemiology in human diseases.

Current knowledges about time-dependent variations in onset of several acute medical diseases are briefly reviewed. Moreover, temporal variation in relative risk factors are also discussed. Any clue to the increased likelihood of a given event can heighten suspicion and shorten time of effective action. The predictability of a certain event, due to the periodicity of cyclic changes, can be of a practical interest in everyday medical practice.

Cardiovascular Diseases↗
PubMed1993

[The incidence of acute myocardial infarct during the week. A chronobiological evaluation].

Several diseases, and particularly cardiovascular affections, show a periodic fluctuation in their occurrence. We investigated acute myocardial infarction (AMI) incidence in connection with the day of the week, looking for a link with psycho-social phenomena. Eight hundred and fifty-two patients with AMI were considered: they had been admitted to the emergency department of two main towns of northeastern Italy during a calendar year. Eight hundred and seventeen (533 men, 284 women) were eligible for the purpose of this study. The time of symptom onset was recorded, cardiovascular risk factors and occupational condition were evaluated. All data were analyzed through chi-square test of uniformity and Halberg single cosinor test. No statistically significant difference from the uniform distribution appeared in acute events occurrence both in patients as a whole and in single subgroups subdivided according to gender and age. However, the preferential distribution during the days of the week was somewhat different between men (highest incidence at the extreme of the week) and women (highest incidence about mid-week). Statistically significant differences in AMI occurrence in the week were evidenced when patients were analyzed after subdivision according to their occupational condition: working subjects, in comparison with not-working individuals, showed a higher AMI incidence at the beginning of the week with respect to subsequent days. It is therefore likely that the stress associated with the return to work (according to the weekly working pattern of western society) represents an additional important cause of AMI. The mechanisms for that are only speculative.

Aged↗
PubMed1992

Abundance of the primary transcript and its processed product of growth-related genes in normal and leukemic cells during proliferation and differentiation.

The relative abundance of primary transcript and mature mRNA of the c-myc, calcyclin, S14 ribosomal protein, and rRNA genes was determined densitometrically after reverse transcriptase-polymerase chain reaction and Northern blotting analysis in resting and mitogen-stimulated lymphocytes, proliferating and terminally differentiated HL-60 cells, and leukemic blast cells. Transcription and processing of c-myc and rRNA gene transcripts increased proportionally after mitogen stimulation, whereas these processes were independent of cell cycling status in the case of the S14 gene. Normal lymphocytes showed an unexpectedly large amount of primary transcript of the calcyclin gene, whereas the corresponding mRNA was undetectable. The abundance of c-myc, calcyclin, and S14 mRNA in terminally differentiated HL-60 cells decreased sharply, compared to their proliferating counterparts. This decrease reflected post-transcriptional modulation, since the abundance of precursor remained essentially unchanged. After HL-60 differentiation, the 32S rRNA levels remained relatively high, whereas the 45S primary transcript almost disappeared. Leukemic blast cells displayed highly variable precursor/mRNA ratios of c-myc, calcyclin, and S14 genes but consistently high ratios of 32S to 45S RNA, suggesting that the cleavage rate of the 32S rRNA was sharply reduced in these cells, resulting in an accumulation of this molecule. These results suggest the importance of efficient processing of primary transcript to generate adequate functional mRNA, thus regulating gene expression. Furthermore, in terminally differentiated cells and leukemic blast cells a stabilization of the primary transcript without efficient processing can be observed. The role of the stabilization of the primary transcript in terminal differentiation is further supported by the results of run-off transcription, indicating a sharp decrease of c-myc and calcyclin transcription rate in retinoic acid/dimethyl sulfoxide-treated HL-60 cells.

Acute Disease↗
PubMed1992

Sudden death from pulmonary thromboembolism: chronobiological aspects.

The aim of this study was to determine whether sudden cardiac death from pulmonary embolism exhibits any chronobiological rhythm. Five hundred and seven consecutive subjects dying suddenly outside of hospital and brought into our Emergency Department from January 1983 to December 1989 were studied. The time and date of event were accurately recorded. All subjects underwent autopsy and 48 of them were found to have died of pulmonary embolism (23 males, mean age 73.9 +/- 8 years and 25 females, mean age 76 +/- 12 years). All data were analysed by means of single cosinor[19,20]. In the subjects with pulmonary emboli both a circadian and a circannual rhythmicity were found, with a significant acrophase respectively in the morning (h.min. 11.46, P = 0.003) and in winter (-19.3, P = 0.009).

Aged↗
PubMed1992

Acute and chronic nitrendipine administration in essential hypertension: a chronobiologic study.

To evaluate the chronobiologic pattern of the hypotensive effect of nitrendipine, 10 patients with mild-to-moderate arterial hypertension were studied. They received a randomized single dose (20 mg) of nitrendipine and placebo, and 20 mg of nitrendipine daily for 2 months. Systolic and diastolic blood pressure (SBP and DBP, respectively) and heart rate (HR) were measured for 24 h using an automatic noninvasive device. The data were analyzed by single and mean cosinor methods and by ANOVA and Student's paired t test. Chronic administration of nitrendipine resulted in a more effective lowering of the SBP and DBP mesor, compared with placebo and acute administration, preserving the circadian rhythms. The preservation of the HR circadian rhythm agrees with the lack of interference of the drug with neurohormonal mechanisms.

Adult↗