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Biomedical subjects

R Manfredini

Publications and source records attributed to R Manfredini.

At least 91 records · Page 5Linked to original sources

Baroreflex sensitivity, but not heart rate variability, is reduced in patients with life-threatening ventricular arrhythmias long after myocardial infarction.

Low values of heart rate variability (HRV, a marker of vagal tone) and baroreflex sensitivity (BRS, a marker of vagal reflexes) identify patients at higher risk soon after myocardial infarction (MI). However, it is still unknown whether HRV and BRS correlate with malignant arrhythmias after the recovery from the transient post-MI autonomic disturbance. This study assessed whether HRV and BRS would differ in patients with malignant ventricular arrhythmias occurring long after MI compared with those in a control population. Twenty-eight patients entered the study: 14 patients with episodes of sustained ventricular tachycardia or ventricular fibrillation occurring more than 1 year after MI, age (mean +/- SEM) 64 +/- 2 years, and left ventricular ejection fraction 34% +/- 3% (VT/VF group) were compared with 14 similar patients with no ventricular tachycardia (control group). Mean RR interval was not different in the two groups (844 +/- 37 msec in VT/VF and 892 +/- 24 msec in control group). Also, no difference was found in any time- or frequency-domain measure of heart rate variability. However, patients in the VT/VF group had a significantly lower baroreflex sensitivity compared with patients in the control group (4.2 +/- 0.5 vs 8.0 +/- 1.1 msec/mm Hg, p = 0.008). Thus BRS but not HRV was reduced in patients with life-threatening ventricular arrhythmias occurring long after MI. A persistent depression of vagal reflexes may play a role in the occurrence of malignant arrhythmias, and analysis of BRS may potentially be helpful in the identification of patients at high risk long after myocardial infarction.

Aged↗

Time-dependent effect of isradipine on the nocturnal hypertension in chronic renal failure.

Nocturnal hypertension is frequently observed in chronic renal failure and contributes to the risk of target organ damages. We assessed whether antihypertensive therapy may restore a nocturnal blood pressure (BP) fall in this condition. A sustained-release oral formulation (SRO) of isradipine was used, and the possible differences in the response to morning nu evening dosing were also investigated. Sixteen hypertensive patients with chronic renal failure due to parenchymal kidney disease were studied after 2 weeks of single-blind placebo runin. According to the double-blind, randomized, cross-over design, they received 5 mg isradipine SRO at 08:00, or at 20:00 for 4 weeks, separated by a single-blind placebo period of 2 weeks. A 24-h BP monitoring at 10-min intervals was carried out at the end of each treatment using a SpaceLabs 90207 instrument. Under placebo, blunt BP profiles were observed, whereas HR showed a mean nocturnal fall of 17.4%, which remained unaltered after isradipine. Both isradipine treatments were equally effective in reducing the mean 24-h BP levels. However, the evening regimen showed a more pronounced effect during the night. The mean nocturnal fall in systolic/diastolic BP represented 4.8/8.7% and 7.5/10.9% of the corresponding daytime mean after morning and evening dosing, respectively. Only the evening administration reset the normal synchronization of the 24-h BP and HR profiles. Our findings demonstrate that antihypertensive treatment may restore a nocturnal BP fall in renal patients. An evening regimen of isradipine SRO seems more apt than a morning regimen to obtain this therapeutic goal.

Antihypertensive Agents↗

Dissociated 24-hour patterns of somatotropin and prolactin in fatal familial insomnia.

To assess the changes in the 24-hour profiles of serum somatotropin and prolactin levels during total disruption of the sleep/wake cycle sustained over several months, we studied 2 subjects affected by fatal familial insomnia, a rare disease characterized by selective thalamic degeneration that causes chronic sleep loss. Under standardized conditions and polysomnographic control, the patients underwent repeated 24-hour study sessions covering the entire clinical course of the disease. Hormones were assayed at 30-min intervals. Four healthy volunteers were used as controls. A sleep/wake cycle was always absent in fatal familial insomnia. Serum somatotropin and prolactin concentrations never exceeded the normal range of variation. The nocturnal elevation of somatotropin disappeared simultaneously with sleep loss, whereas a significant 24-hour component of variations in serum prolactin levels was present for months after total disruption of the sleep/wake cycle, with normally placed nocturnal acrophases. Complete obliteration of the 24-hour component was achieved for prolactin only in the advanced stages, through a progressive decrease in 24-hour amplitude of variation. Selective and progressive degeneration of the mediodorsal and anterior ventral nuclei of the thalamus causes an early obliteration of the 24-hour rhythm of somatotropin and a later disappearance of circadian prolactin rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circadian variation in the occurrence of paroxysmal supraventricular tachycardia in clinically healthy subjects.

The purpose of this study was to assess prospectively the circadian distribution of spontaneous paroxysmal supraventricular tachycardia (PSVT) in drug-free subjects with no previous history or symptoms and signs of concomitant heart or lung disease. Of 112,424 presumably diurnally active patients admitted to the Emergency Department of a city hospital during a 2-year period (1990-1991), a total of 185 patients were screened with these characteristics. Time of symptom onset was exactly recordable in 177 (75 men and 102 women). Analysis of variance documented a higher incidence in the morning-afternoon hours. Cosinor analysis, although not a perfect method for the time series analysis, verified circadian rhythmicity with afternoon peak times. Our findings suggest that a circadian pattern in intrinsic electrical instability of the heart conduction system exists irrespective of the circadian fluctuations in the pathophysiologic mechanisms of the cardiovascular or lung diseases most frequently associated with PSVT itself.

Adult↗

Role of c-fes protooncogene in myeloid differentiation.

The main purpose of this report is to provide a review of the present knowledge on the structure, function, and possible regulatory role of c-fes in the genetic programs underlying the proliferation and differentiation of hematopoietic myeloid cells. Fes encodes a non-receptor tyrosine kinase that is highly expressed in immature and differentiated cells of the granulocytic and mono-macrophagic lineages. It is therefore possible that c-fes is involved in the signal transduction of myeloid cell differentiation, even if the specific substrates phosphorylated by this protooncogene are only poorly characterised. Several experimental models have been established to evaluate the role of c-fes in myeloid differentiation, in particular: the differentiation capacity of HL60 cells lacking the p92(c-fes) protein, the transfection of c-fes gene into K562 cells and transgenic animals overexpressing c-fes. The results obtained point to the importance of c-fes in myeloid cells, since it appears to be involved in granulocytic maturation as an antiapoptotic gene, and in macrophagic maturation as a regulatory gene.

Journal Article↗

All-trans-retinoic acid induces simultaneously granulocytic differentiation and expression of inflammatory cytokines in HL-60 cells.

All trans-retinoic acid (ATRA) can induce granulocytic differentiation both in vitro and in vivo, and its activity is mediated by the retinoic acid receptor-alpha (RAR-alpha). In the present study, we evaluated the ability of this inducer in HL-60 cells, to stimulate simultaneously granulocytic differentiation and the expression of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-3, IL-6, tumor necrosis factor-alpha (TNF-alpha), and stem cell factor (SCF). The level of expression of these cytokines in ATRA-treated HL-60 cells was compared with that observed in normal and lipopolysaccharide (LPS)-treated peripheral granulocytes. The results indicate that the expression of these cytokines is enhanced during differentiation so that the pattern observed in ATRA-treated HL-60 cells is close to that of LPS-stimulated normal granulocytes. In addition, tetra phorbol acetate (TPA)-treated HL-60 cells express several of the above listed cytokines. It is concluded that ATRA not only induces granulocytic differentiation of HL-60 cells, but also activation of these terminally differentiated cells. The activating cytokine expression in these cells appears related to the progress of the differentiation program induced by ATRA since normal granulocytes do not respond to this inducer by activation of the expression of these genes. Furthermore, the cytokine activation is a specific effect of ATRA, since DMSO does not have any stimulatory effect.

Base Sequence↗

Angiovideo-assisted hemodynamic correction of varicose veins.

OBJECTIVE: Evaluation of the feasibility and utility of angioscopy in the hemodynamic correction (French acronyms is CHIVA) of primary varicose veins disease. EXPERIMENTAL DESIGN: Prospective evaluation of 25 patients, undergoing hemodynamic correction of primary varicose disease with intraoperative videoangioscopic guide. Patients have been selected according to criteria emerged from a prospective study that we had previously conducted. Follow-up lasted 1 year (range 8-18 months). SETTING: Department of Surgery, University of Ferrara, Italy. Institutional practice. One-day surgery. PATIENTS: Their selection has been carried out in our Vascular Laboratory. The adopted clinical criteria of selection were: Primary varicose disease of the long saphenous vein territory, no previous thrombophlebitis and/or sclerotherapy. Doppler cw and Duplex criteria followed were: competent deep venous system, long saphenous vein diameter minor than 10 mm and incompetent perforating veins diameter minor than 4 mm. INTERVENTIONS: 25 hemodynamic corrections according to the CHIVA method described by Franceschi. An angioscope, introduced through a distal collateral of the long saphenous vein, permitted the precise interruption of the venous-venous shunts and of the superficial venous system, just below the perforators chosen as re-entry points in the deep venous system. MEASURES: Clinical: varices and symptomatology reduction. Duplex and Doppler cw: detection of the superficial blood flow re-entry, in the deep venous system, through the perforators and identification of recurrences or new refluxes. Pre and postoperative Ambulatory Venous Pressure and Refilling Time have also been measured. RESULTS: In 20 patients symptoms and varices relief were recorded (80%), in 5 patients varices reduction was observed only during walking (20%). In 2 of these latter patients there was no re-entry through the perforators, with a recurrent sapheno-femoral reflux in 1 of them. Early complications recorded were: 2 long saphenous vein thrombosis (8%); 7 ecchimosis (28%) when heparine/saline solution had been used for angioscopic clearance. CONCLUSIONS: Intraoperative angioscopy is feasible and useful when the hemodynamic situation is complex and the Duplex map is difficult to be interpreted by the surgeon. In this series the second look percentage rate has been minor compared to the percentage rates published so far by other authors.

Adolescent↗

[Acute anterior myocardial infarction in a patient with left atrial myxoma during pregnancy].

It is a case report of a patient who had an acute anterior myocardial infarction during the 22th week of pregnancy, probably due to coronary embolization from a large left atrial myxoma. The patient had a previous operation for a right adrenal adenoma causing a Cushing Syndrome. It is hypotized an association between adrenal adenoma and atrial myxoma, like "Carney Syndrome".

Adenoma↗

Emergency admissions of opioid drug abusers for overdose: a chronobiological study of enhanced risk.

STUDY OBJECTIVE: To determine whether there is a specific temporal risk for opioid drug overdose. DESIGN: To study patients presenting to the ED in a comatose state from accidental drug opioid overdose. PARTICIPANTS: Two hundred seventy-four patients were admitted to the ED of the Hospital of Ferrara, Italy, from 1988 to 1990, 225 men (82.1%; mean age, 25 +/- 3.4 years) and 49 women (17.9%; mean age, 23.5 +/- 2.8 years). INTERVENTIONS: Month, day, and hour and minute of admissions were recorded, and time-qualified frequency data were analyzed by the single cosinor method. RESULTS: Cosinor analysis demonstrated a significant circadian rhythm for both the total number of observations and the separate male and female subgroups with an early evening peak ("acrophase") at about 7:00 PM. No significant circannual rhythm was evident, but for the total group a significant 6-month rhythm was demonstrable with peaks in late November and late May. CONCLUSION: There is a distinct "chronorisk" of opioid drug overdose in the early evening hours.

Adult↗

Expression and function of nerve growth factor and nerve growth factor receptor on cultured keratinocytes.

Keratinocytes, a key cellular component both for homeostasis and pathophysiologic processes of the skin, secrete a number of cytokines and are stimulated by several growth factors. Nerve growth factor (NGF) is synthesized in the skin and basal keratinocytes express the low-affinity nerve growth factor receptor (NGF-R). We present evidence that normal human keratinocytes in culture express the low- and the high-affinity NGF-R both at the mRNA level, as determined by reverse-transcription polymerase chain reaction and at the protein level, as shown by cytofluorimetric analysis. NGF significantly stimulates the proliferation of normal human keratinocytes in culture in a dose-dependent manner. This effect can be prevented by the addition of both an anti-NGF neutralizing antibody and a high-affinity NGF-R (trk) specific inhibitor, the natural alkaloid K252a. By contrast, keratinocyte proliferation is not inhibited by an anti-low-affinity NGF-R monoclonal antibody, thus suggesting that NGF effect on human keratinocytes is mediated by the high-affinity NGF-R. Moreover, NGF mRNA is expressed in normal human keratinocytes and NGF is secreted by keratinocytes in increasing amounts during growth, as detected by enzyme-linked immunosorbent assay. These results suggest that NGF could act as a cytokine in human skin and take part in disorders of keratinocyte proliferation.

Antibodies, Monoclonal↗

Expression of B7 costimulatory molecule in cultured human epidermal Langerhans cells is regulated at the mRNA level.

Langerhans cells (LC) belong to the dendritic cell lineage and are the principal antigen-presenting cells of squamous epithelia. Short-term cultured LC (cLC) exhibit a marked augmented capacity to stimulate allogeneic T cells and acquire the ability to activate naive T cells, probably in relation to enhanced expression of accessory signals. In this study, we evaluated the expression of B7 costimulatory molecule (CD80) in human freshly isolated (fLC) and cLC at both the protein and mRNA level. Staining of frozen skin sections did not reveal any epidermal dendritic cell reactive with either of two different anti-B7 monoclonal antibodies. fLC in suspension did not exhibit any B7 staining as evaluated by two-color flow-cytometry analysis and immunoelectron microscopy. In contrast, LC that were cultured for 24-72 h displayed strong surface B7 reactivity with a characteristic patchy pattern. Treatment with dispase and trypsin did not reduce B7 staining of cLC. Following warming to 37 degrees C, cLC tagged with anti-B7 monoclonal antibody and gold-conjugated secondary antibody could internalize surface B7 by using the organelles of receptor-mediated endocytosis. B7 mRNA, detected by the reverse-transcriptase polymerase chain reaction technique, was expressed at a low level in purified (> 90% HLA-DR+) fLC but not in LC-depleted epidermal cells, and was markedly upregulated in purified cLC. The results indicate that 1) fLC do not express B7 protein on their surface, but acquire B7 during culture, 2) surface B7 is not sensitive to trypsin, 3) B7 expression is regulated primarily at the mRNA level, and 4) membrane B7 can be internalized within cLC. B7 molecule on CLC may be relevant to their increased antigen-presenting cell potency and ability to stimulate naive T lymphocytes.

Antibodies, Monoclonal↗

Acute intracerebral haemorrhage: circadian and circannual patterns of onset.

Hypothesis of the circannual and circadian variation in onset of intracerebral haemorrhage (CH) was verified, by means of single cosinor method and chi-square test for goodness of fit, in 161 consecutive patients (94 men and 67 women) admitted into the Institute of Neurosurgery of Ferrara Hospital, Italy, over 9 years. The majority of CH occurred in the morning between 06.00 AM and 12.00 noon (36.7% of cases, p < 0.001); when considering the specific anatomical sites, typical supratentorial haemorrhages showed a similar pattern (37.4%, p = 0.01). A similar morning behavior was found when considering subgroups by sex (men 36.2%, women 37.3%), age > or = 60 years (42.5%), no presence of hypertension (39.7%), no presence of diabetes mellitus (33.3%) and non-smokers (30.4%). The results by cosinor analysis yielded a circadian rhythmicity both for total sample and, for the men's subgroup, with a morning peak at 11.44 and 11.25, respectively. For women, however, spectral analysis found a significant ultradian cycle, having a period of 12 h (p = 0.01). A circannual periodicity, with a prevalent peak in February, was found for total sample and males subgroups, too. The results of this study confirm that intracerebral haemorrhages present a characteristic circadian and circannual pattern in onset.

Adult↗

Circadian variation in the occurrence of fatal pulmonary embolism. Differences depending on sex and age.

Published studies have indicated a circadian variation in the occurrence of several acute cardiovascular events, e.g., myocardial ischemia, myocardial infarction, sudden cardiac death and cardiac arrest. The aim of this study was to determine if there is a circadian variation in the occurrence of fatal pulmonary embolism, and to evaluate possible differences in the temporal pattern in relation to sex and age. 230 cases of fatal pulmonary embolism (74 out-of-hospital and 156 hospitalized) observed in a general hospital over a 9-year period were considered. The total sample was stratified both by sex and into four groups by age including, respectively, subjects aged less than 60 years (group A), between 60 and 69 (group B), between 70 and 79 (group C) and 80 years and over (group D). The data were analyzed by the single cosinor method. A significant morning pattern was found for the total population (p = 0.011), females (p = 0.033), and age subgroups C and D (p = 0.015 and 0.008), with respective acrophases at 11.57, 11.23, 10.54 and 13.24. A morning pattern in the onset of fatal pulmonary embolism is confirmed for the total population, although sex and age seem also to play an important role.

Age Factors↗