Medical fiction could be misleading.
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Emergency Service, Hospital↗
Biomedical subjects
R Manfredini
Publications and source records attributed to R Manfredini.
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↗
Circadian variation in spontaneous rupture of abdominal aorta.
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Aged↗
Seasonal variation in the onset of acute microcrystalline arthritis.
OBJECTIVE: To determine whether acute attacks of uric acid and calcium pyrophosphate microcrystalline arthritis show a seasonal variation and, if so, to verify whether the distribution of single episodes shows a rhythmic circannual pattern. METHOD: All suspected cases of microcrystalline acute arthritis observed at the General Hospital of Ferrara during an 8 yr period (January 1990-December 1997) were considered. Diagnosis was made on the basis of history, physical examination and analysis of synovial fluid by means of polarized light microscopy. Month and day of each event were categorized both into four 3-month periods (by seasons) and 12 monthly intervals. Two different statistical methods have been utilized: chi(2) test for goodness of fit and partial Fourier series. RESULTS: During the period considered, 210 episodes of acute gout were observed [196 in males (93.3%) and 14 in females (6.7%)] in 179 different subjects, and 179 episodes of acute pseudogout [58 in males (32.4%) and 121 in females (67.6%)] in 165 different subjects. Gout attacks showed a higher frequency peak in spring [76 cases (36. 2%), P<0.001]. Analysis of distribution of events by gender confirmed the clear spring pattern in males (36.2%), whereas the paucity of cases in females did not allow any valid statistical analysis. Pseudogout attacks showed a higher frequency peak in autumn [52 cases (29.1%)], without reaching a statistically significant level either for the total sample or for subgroups divided by gender. Analysis of the seasonal distribution of gout or pseudogout events was significantly different (chi(2) 15.7, P=0.001). Chronobiological evaluation by means of Fourier analysis showed a circannual pattern for gout attacks, both for the total sample (P=0.006) and the male subgroup (P=0.003), characterized by a peak in April and a trough in October. Again, as for pseudogout events, no seasonal variation was found, either for the total sample or subgroups by gender. CONCLUSIONS: The present study gives further confirmation that acute gout attacks exhibit a circannual distribution in their occurrence, being more frequent in April, whereas pseudogout attacks do not. Moreover, the seasonal distribution of gout and pseudogout acute events is significantly different.
Acute Disease↗
From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events.
A growing body of evidence substantiates that the occurrence of cardiovascular events in unevenly distributed in time, especially during the 24 h. These temporal patterns are indicative of temporal variation in the (1) pathophysiological mechanisms that trigger cardiovascular events and (2) physiological status of the cardiovascular system, which combine to give rise to 24 h and other periodicities in the susceptibility to disease. The classic assumption of epidemiologic studies is constancy (or homeostasis) in one's risk to disease during the 24 h, as well as other, time domains. However, we propose a new concept, that of chronorisk since it takes into account the temporal variability in the pathophysiological mechanisms and their reciprocal temporal interactions that lead to day-night and other time-dependent patterns in cardiovascular events. This chronobiological approach, which is expected to contribute new insight into the prognostic and therapeutic assessment of cardiovascular events, is worthy of broader application in cardiovascular and other fields of medicine and warrants further investigation.
Cardiovascular Diseases↗
Circadian variation in the onset of acute critical limb ischemia.
Research has identified a circadian rhythm for several acute thrombotic cardiovascular and cerebrovascular diseases. We investigated the possible existence of a circadian variation in the onset of acute critical limb ischemia. Out of a consecutive series of 198 cases, precise determination (within 30 minutes) of the time of symptom onset was possible in 156 (78.8%). Partial Fourier series were applied to hourly data and the best-fitting curves for circadian rhythmicity were calculated. Both in the total population and in subgroups by gender and location of ischemia, a highly significant circadian pattern of occurrence was demonstrated with peak in the morning (approximately 0800) and nocturnal minimum around midnight. This study is the first demonstration of the circadian pattern of acute arterial occlusion of the limbs, in agreement with several studies showing a circadian pattern to the time of onset of acute myocardial infarction and other unfavorable acute events related to thrombosis. This opens up the potential for therapeutic implications, suggesting the need to adjust the dose of drugs based on the time of day. Further studies dealing with circadian variation in the efficacy of thrombolytic agents are so needed.
Acute Disease↗
In vitro versus in vivo assessment of vein wall properties.
Venous compliance reflects the mechanical properties of the vein wall. Clinical methods of measurement have not been validated by comparison with the accepted in vitro measurement. Despite this, clinical assessment of vein compliance may have a series of useful applications: (1) to assess the progression of chronic venous insufficiency and the related hemodynamic forces acting on the saphenous vein wall; (2) to determine the suitability of the saphenous vein for replacement of an arterial conduit by testing its mechanical properties; and (3) to select the saphenous vein with preferable mechanical performance for coronary artery bypass. The aim of this study is to assess the relationship between in vitro and two in vivo methods of compliance measurement. Compliance of the saphenous vein was determined in 20 patients, using both an invasive and a noninvasive (A and B, respectively) method. Duplex scanning was used for diameter measurement. Venous pressure was derived either intravenously with a needle transducer, or noninvasively with limb length measurement. Patients underwent saphenous excision with further in vitro compliance measurement of the same vein segment (method C). The compliance values obtained with the three methods showed different degrees of correlation (r= 0.516, p = 0.0001 for method A versus method C; r = 0.658, p = 0.0001 for method B versus method C; r = 0.993, p = 0.0001 for method A versus method B). The relationships with the in vitro measurements that were determined validate both in vivo methods for assessment of saphenous vein compliance. Due to its completely noninvasive design, method B appears to have potential use for clinical assessment of saphenous vein wall properties.
Biomechanical Phenomena↗
Systemic and topical effects of intradermal hydrofluoric acid.
A 35-year-old man attempted suicide by subcutaneous self-administration of hydrofluoric acid (5 cc of a domestic rust removal solution containing 7% hydrofluoric acid). A burn 9 x 7 cm in diameter immediately appeared at the injection site (left forearm and fold of the elbow). In the emergency department, the burn was copiously washed with isotonic solution and treated with cutaneous and subcutaneous injections of magnesium chloride, 10% solution of calcium gluconate, and 2% xylocaine, then continuously maintained under topical treatment with calcium gluconate. Seven hours after injection, the patient was severely hypocalcemic (Ca+2 0.64 mmol/L). Ten hours after injection, in addition to the persistent hypocalcemia (Ca+2 0.81 mmol/L), hyponatremia (123 mmol/d), hypokalemia (3.4 mmol/L), and hypochloremia (95.6 mmol/L) had developed. The hypocalcemia was corrected with infusion of calcium gluconate (8.92 mEq of Ca+2 as total amount). The patient underwent surgical intervention 7 days after admission, followed by several interventions of plastic surgery.
Adult↗
A needle infixed in the heart.
A 34-year-old man self-fixed a needle into his heart, in the interventricular septum. The foreign body was localized by X-ray, echocardiography, and computed tomography. At surgical opening of the pericardial lamina, the needle was extracted with no need of cutting open the cardiac muscle.
Adult↗
Antisense inhibition of Bax mRNA increases survival of terminally differentiated HL60 cells.
Cell sensitivity to programmed cell death is primarily modulated by members of the Bcl-2 family, as the balance of homodimer or heterodimer formation between proapoptotic and antiapoptotic members defines apoptosis susceptibility in the great majority of cellular contexts. It is, therefore, important to clarify if the Bax protein is limiting for activation of the genetic program of programmed cell death or can be complemented by different Bcl-2 family members, such as Bak or Bad. To gain some insight into the role of Bax in the molecular mechanisms of apoptosis of myeloid cells, we inhibited this gene in all-trans-retinoic acid (ATRA)-treated HL60 cells using the methodology of antisense oligodeoxynucleotides (AS-ODN). Our results indicate that Bax inhibition has no effect on the proliferation and differentiation capacity of HL60 cells. Instead, the survival rate of terminally differentiated Bax-inactivated HL60 (Bax(-) HL60) cells is almost three times higher in respect to control cultures, indicating that in mature granulocytes Bax is not efficiently complemented by others members of the Bcl-2 family proteins.
Apoptosis↗
Circadian rhythms, athletic performance, and jet lag.
Rapid air travel across several time zones exposes the traveller to a shift in his/her internal biological clock. The result is a transient desynchronisation of the circadian rhythm, called jet lag, lasting until the rhythm is rephased to the new environmental conditions. The most commonly experienced symptoms are sleep disorders, difficulties with concentrating, irritability, depression, fatigue, disorientation, loss of appetite, and gastrointestinal disturbance. Apart from the decrements in mental and physical performance directly consequent on such symptoms, competitive athletes are also exposed to the additional negative consequences of a shift from the optimal circadian window of performance. A brief summary of the possible negative effects of jet lag on athletic performance and potentially alleviating strategies is given.
Adaptation, Physiological↗
Chronobiological patterns of onset of acute cerebrovascular diseases.
There is a considerable amount of data indicating that several major unfavorable cerebrovascular events are not randomly distributed over time, but show a peculiar distribution along the day, the week, and the months of the year. The authors review the available evidence on the chronobiological (circadian, weekly, and seasonal) patterns of onset of acute cerebrovascular diseases and variations in their possible triggering mechanisms. The existence of a peculiar chronobiological pattern in the onset of acute cerebrovascular disease, characterized by both circadian (morning and evening occurrence), circaseptan (last and first days of the week), and circannual (especially in winter) is confirmed, although differences depending on biological (gender, age), pathological (diabetes, hypertension, smoke, alcohol), cultural, social, and environmental factors exist. A deeper knowledge of the underlying pathophysiologic mechanisms could provide more effective insights for both preventive strategies and optimization of therapeutic approach.
Age of Onset↗
Impaired baroreflex sensitivity is correlated with hemodynamic deterioration of sustained ventricular tachycardia.
OBJECTIVES: The goal of this study was to evaluate clinical and autonomic variables (heart rate variability and baroreflex sensitivity) related to hemodynamic tolerability of VT in patients with sustained monomorphic VT and a healed myocardial infarction. BACKGROUND: Sustained ventricular tachycardia (VT) with hemodynamic deterioration is associated with a worse prognosis than that of well tolerated VT. The causes of hemodynamic deterioration of VT are incompletely understood. METHODS: Twenty-four consecutive patients with sustained monomorphic VT and a healed myocardial infarction (mean age +/- SD 66 +/- 8 years, left ventricular [LV] ejection fraction 37 +/- 11%) were assigned to group 1 if the VT was well tolerated (n = 11) or to group 2 if faintness or syncope occurred or if systolic blood pressure was < 90 mm Hg with clinical signs of shock (n = 13). RESULTS: No difference was found between the two groups in age, LV function, rate and duration of the VT or heart rate variability. However, patients in group 2 had a significantly lower baroreflex sensitivity (3.4 +/- 1.1 vs. 7.1 +/- 3.7 ms/mm Hg, p = 0.003). Multiple logistic regression analysis showed that only the value of baroreflex sensitivity (p = 0.0003)-but not age, LV ejection fraction, VT cycle length or SD of the RR interval (all p > 0.25)-correlated with the tolerability of the VT. Finally, LV ejection fraction (p = 0.0001) and baroreflex sensitivity (p = 0.0003)-but not age, cycle length of the tachycardia or SD of the RR interval-predicted cardiac death or unstable VT during follow-up. CONCLUSIONS: These data suggest that an impaired cardiovascular reflex response may play a key role in the hemodynamic deterioration of sustained VT and that the evaluation of baroreflex sensitivity in patients at high risk for sustained VT may become useful both in risk stratification and in the individualization of treatment.
Aged↗
Antisense inhibition of c-fes proto-oncogene blocks PMA-induced macrophage differentiation in HL60 and in FDC-P1/MAC-11 cells.
To gain some insight into the role of c-fes in macrophage differentiation, we have analyzed the ability of HL60 leukemic promyelocytic cells and FDC-P1/MAC-11 murine myeloid precursor cells to differentiate in response to phorbol esters after inhibition of c-fes function. Fes inactivation has been obtained by using oligodeoxynucleotides (ODN) complementary to the 5' region of c-fes mRNA and to 5' splice junctions of c-fes primary transcript. After 5 days (d) in culture, in several separate experiments performed with different ODN preparations, a complete inhibition of c-fes expression was observed in HL60 and in FDC-P1/MAC-11 cells. No perturbation of cell growth was evident in our experimental conditions in both cell lines after c-fes inhibition. Furthermore, in HL60 cells lacking c-fes product, an almost complete downregulation of the alpha 4 beta 1 fibronectin receptor occurred. However, in both cell lines, the induction of macrophage differentiation by phorbol esters resulted in an almost complete maturation arrest as evaluated by morphological, cytochemical, immunological criteria, and by the cytofluorimetric cell cycle analysis. A loss of the adhesion capacity of both myeloid cell lines, when compared to terminally differentiated macrophages, was also observed. These results suggest that HL60 and FDC-P1/MAC-11 cells, when treated with phorbol 12-myristate 13-acetate, require c-fes protein expression to activate the genetic program underlying macrophage differentiation.
Animals↗
Circadian rhythmicity in the occurrence of spontaneous acute dissection and rupture of thoracic aorta.
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Aged↗
Ultrasonographic assessment of ambulatory venous pressure in superficial venous incompetence.
PURPOSE: In spite of its invasiveness, measurement of ambulatory venous pressure (AVP) is widely considered the gold standard measurement of venous function. We studied a technique for noninvasive ultrasonographic AVP determination in superficial venous incompetence. METHODS: A linear relationship between venous pressure (measured by echo-guided venous puncture) and diameter (measured by transverse axis duplex imaging) was preliminarily demonstrated with multiple measurements in different conditions (supine, sitting, standing, and Trendelenburg positions, after exercise with and without cuff occlusion) in a saphenous tract at the thigh of 82 limbs in which reflux had been previously demonstrated. Then AVP was measured in another group of 44 patients who had demonstrated superficial venous incompetence, both with and without proximal occlusion, using again the same invasive method and a new noninvasive technique. The latter technique consisted in the construction of a linear diameter/pressure curve obtained after saphenous diameter (by high-resolution sonography) and noninvasive pressure (using hydrostatic values) determinations in the sitting and standing positions. Further measurement of saphenous diameter after standardized exercise permits extrapolation of the AVP values from the curve. RESULTS: Linear regression analysis demonstrates that (1) beginning from 20 mm Hg, the pressure/diameter relationship of the incompetent greater saphenous vein is linear; and (2) AVP values derived invasively and noninvasively are significantly correlated (r = 0.7347 and p < 0.0001 for AVP derived without occlusion; r = 0.7270 and p < 0.0001 for values recorded with occlusion). CONCLUSIONS: The proposed technique appears able to reliably assess noninvasively AVP values in superficial venous incompetence. In addition, it can be performed with equipment that is widely used for vascular investigations.
Exercise↗
Undiagnosed sleep-disordered breathing among male nondippers with essential hypertension.
OBJECTIVE: A blunting of the nocturnal fall in arterial blood pressure is found in a minority of patients (nondippers) with essential hypertension. We tested whether sleep-disordered breathing (snoring and apnea or hypopnea) might explain such a finding for male patients, among whom its prevalence is much higher. SETTING AND PATIENTS: We studied 100 new cases of hypertension in men, observed consecutively by a local group of general practitioners and diagnosed essential hypertensives in a referral clinic. By using 24 h ambulatory blood pressure monitoring with a SpaceLabs 90207 device, 15 patients were classified initially nondippers (daytime ambulatory blood pressure > or = 136/87 mmHg; night-time decrease by < 10% of the daytime mean), but only 11 were confirmed to be nondippers by continuous blood pressure monitoring with a Finapres device. Ten dippers matched by age, body mass index and mean 24 h blood pressure were used as controls. MAIN OUTCOME MEASURES: Parameters of nocturnal polysomnography. RESULTS: During polysomnography, the nondippers exhibited a blunting of the sleep-related fall in blood pressure and an increased variability in blood pressure associated with sleep-disordered breathing (heavy snoring for all, with an apnea or hypopnea index > 10 in 10 cases). Six of the control patients breathed normally and four snored nonapneically. There was a normal fall in nocturnal blood pressure in all 10 cases. CONCLUSIONS: The nondipper condition appears to be associated with undiagnosed apneic snoring for an unselected population of previously untreated male subjects with a diagnosis of essential hypertension. Ambulatory blood pressure monitoring of such patients is of limited diagnostic value.
Adult↗
Neuropsychological deficits in asymptomatic atrial fibrillation.
OBJECTIVE: To assess the preclinical effects on cognitive functions of nonrheumatic atrial fibrillation (NRAF) in patients with negative history for cerebrovascular disease. MATERIALS AND METHODS: The study included 37 consecutive patients with chronic (n=16, mean age 65.3+/-6.6 years) or paroxysmal (n=21, mean age 58.3+/-9.5 years) NRAF and an equal number of control subjects in sinus rhythm, who were matched for age, education and presence of hypertension. A comprehensive neuropsychological battery including tests of attention, memory, language and visuospatial skills was administered. RESULTS: Patients with chronic NRAF showed significantly poorer performances in tasks exploring attention and verbal memory functions, while the paroxysmal group was significantly impaired in a long-term memory task. The neuropsychological findings were confirmed excluding from both groups patients with CT evidence of cerebrovascular damage. A small subgroup of patients was also submitted to cerebral MRI. CONCLUSION: Neurologically asymptomatic NRAF is related to a subclinical but significant impairment in attention and memory. These deficits could be produced by minor ischemic lesions due to microembolization, or by diffuse hypoxic damage due to hypoperfusion.
Adult↗