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Biomedical subjects

Sandro Forconi

Publications and source records attributed to Sandro Forconi.

13 recordsLinked to original sources

A "fat" cough.

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Cardiac Surgical Procedures↗

Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members.

BACKGROUND AND PURPOSE: Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. SUMMARY OF REVIEW: CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. CONCLUSIONS: At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Aged↗

Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study.

BACKGROUND: Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (P=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9+/-1.1%; after IR: 1.2+/-0.7%, P<0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0+/-0.9%; after IR: 6.2+/-1.1%, P=NS; P<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 10.3+/-1.5%; after IR: 1.3+/-1.4%, P<0.05). CONCLUSIONS: In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K(ATP) channels. Further studies are needed to test the potential clinical implications of this finding.

Adult↗

Folic Acid does not limit endothelial dysfunction induced by ischemia and reperfusion: a human study.

Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7+/-1.0%; after IR, 1.5+/-1.3%, P<0.01). A similar effect was observed in the folic acid group (before IR, 6.3+/-1.1%; after IR, 2.1+/-1.0%, P=ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.

Blood Flow Velocity↗

The role of reactive free radicals in ischemic preconditioning--clinical and evolutionary implications.

Ischemic preconditioning is a condition of reduced sensitivity to ischemic damage. This protective state can be induced by exposure to periods of brief, sublethal, ischemia prior to a protracted ischemic event, but, more interestingly, also by administration of specific drugs. Recent studies have emphasized the central role of free radicals (including superoxide anion and nitric oxide) in this process. In line with these observations, studies have demonstrated that also drugs such as organic nitrates, which are able to release nitric oxide (but also the highly oxidant superoxide anion) can induce preconditioning. Starting from our observations made in human experimental models regarding the effects of chronic therapy with organic nitrates, we criticize the hypothesis whereby nitrates might be used to induce a state similar to preconditioning upon chronic exposure. As well, we propose a theory for the evolutionary meaning of ischemic preconditioning based on the hypothesis that, while protective over short periods of time, continuous exposure to oxidant free radicals might be associated with a loss of this protective effect and, in certain cases, with an increased oxidative damage.

Biological Evolution↗

Current perspectives. Therapy with organic nitrates: newer ideas, more controversies.

Because of their potent hemodynamic effects, organic nitrates have been introduced in the cardiovascular pharmacopoeia since more than a century in the treatment of coronary artery disease and congestive heart failure. Today, nitroglycerin is the most commonly prescribed generic drug in Italy. While their hemodynamic effects and some of their side effects (e.g. nitrate tolerance, the rebound phenomenon) are at least in part known, little is known regarding other effects of nitrates, for instance their antiaggregant, preconditioning-mimetic, and antiatherosclerotic properties. These effects might have tremendous importance in the treatment of cardiovascular patients. At the same time, the effects of nitrate-derived oxygen free radical species require further investigation. This review provides an update on recent findings in this field.

Cardiovascular Diseases↗

Pulmonary embolism in very old patients.

BACKGROUND AND AIMS: Diagnosis of pulmonary embolism (PE) in the elderly remains difficult and is often late, although its incidence increases steadily with age. Since few studies have reported the clinical picture of this disease in very old patients, the aim of our study was to focus on clinical, instrumental and laboratory aspects in patients 75 years of age and over with suspected PE. METHODS: Symptoms, signs, risk factors for venous thromboembolic diseases, 12-lead electrocardiograms, B-mode echocardiograms, chest X-rays, leg compression venous ultrasonography, latex-assay quantitative D-dimer, and arterial blood gas analyses were collected for 96 elderly patients of 75 years and over (mean age 81.22 +/- 4.81) with suspected PE, admitted to our acute geriatric ward from 1997 to 2000. Patients were divided into two groups: 59 patients with PE (PE+) confirmed by pulmonary angiography, scintigraphic lung scan or necropsy, and 37 patients with normal lung scan or without PE at necropsy (PE-). RESULTS: Dyspnea and chest pain were the most common symptoms in both groups, but significantly more frequent in the PE+ group. Tachycardia, fever, cyanosis, and tachypnea were the most common objective signs in both groups; tachycardia and tachypnea were not significantly different between the two groups. Bed rest, venous insufficiency and leg deep vein thrombosis were the most common venous risk factors in PE+ and significantly different with respect to PE-. Sinus tachycardia, ST-T abnormalities and right bundle branch block were the most common electrocardiographic aspects in PE+; echocardiograms showed significantly more frequent acute involvement of right heart in PE+, whereas chest X-rays were rarely compatible with PE and did not reveal differences between the two groups. D-Dimer was significantly higher in PE+ but was below 500 ng/mL only in 25% of cases in PE-. More severe hypoxemla, oxy-hemoglobin hyposaturation and increased alveolar-arterial oxygen gradients were found at arterial blood gas analysis in PE+. CONCLUSIONS: Although many analyzed clinical, instrumental and laboratory aspects were significantly more frequent in the PE+ group, they were all non-specific and not conclusive for diagnosis of PE. Our retrospective study focus may add information about the picture and diagnostic difficulties of PE in very old patients.

Age Factors↗

[Diagnostic and therapeutic features of pulmonary embolism in elderly patients].

BACKGROUND: Pulmonary embolism (PE) is often underdiagnosed in the elderly for nonspecificity and atypicity of presentation. The aim of this study was to evidence, retrospectively, the clinical, instrumental and laboratory aspects in the diagnosis of elderly patients with suspected PE and to observe the antithrombotic primary prophylaxis, acute antithrombotic treatment and its hemorrhagic side effects in patients with confirmed PE (CPE). METHODS: We conducted an observational, retrospective, study on 118 hospitalized patients > or = 65 years (49 males and 69 females, mean age 77.76 +/- 7.17 years) during a 5-year period who underwent a scintigraphic lung scan for suspected PE. Clinical, instrumental and laboratory findings of 75 patients with CPE were compared with 43 patients with unconfirmed PE (UCPE). RESULTS: Symptoms of dyspnea and chest pain and all the considered signs, except tachycardia, were significantly more frequent in the CPE group. Bed rest > 4 days, venous insufficiency, deep vein thrombosis, obesity and stroke were the risk factors significantly more frequent in the CPE group. Sinus tachycardia, incomplete right bundle branch block, ST-T alterations were significantly more present in the CPE group. Cardiomegaly was the only significant more frequent chest X-ray finding in the CPE group, while echocardiography showed a significant involvement of the right ventricle in the CPE group. Plasma D-dimer levels were significantly higher in the CPE group but the mean values were > 500 micrograms/l in both groups. In arterial blood gas analysis we found more severe hypoxemia, arterial hyposaturation and higher alveolar-oxygen gradient in the CPE group, while we did not find a more frequent respiratory alkalosis in this group. Heart failure, ischemic heart disease and chronic obstructive pulmonary disease were the more frequent diagnoses in the UCPE group. None of the patients received thrombolysis. Seventy percent of the CPE patients received intravenous heparin; 9 hemorrhagic side effects occurred, 3 of them being major with one fatal in one patient treated with subcutaneous unfractionated heparin. CONCLUSIONS: Our study shows the diagnostic difficulties of PE in the elderly because of nonspecifcity of clinical, instrumental and laboratory aspects. Although many of these aspects are significantly more frequent in the CPE group, the same are often the main aspects also in the UCPE group. Moreover, our study reveals the low utilization of antithrombotic primary prophylaxis and high risk of hemorrhagic side effects of heparin in this subgroup of patients.

Age Factors↗

High levels of human chromogranin A in umbilical cord plasma and amniotic fluid at parturition.

OBJECTIVE: The human placenta is a neuroendocrine organ that produces several hypothalamic and pituitary hormones that are secreted during pregnancy and parturition into maternal and fetal circulation and amniotic fluid. Human chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla and released in response to several stressful events. During pregnancy, intrauterine tissues express and synthesize CgA mRNA and peptide and secret it into the biologic fluids of pregnancy, so we investigated whether maternal, umbilical, and amniotic human CgA levels are affected by the stress of parturition. METHODS: We measured pregnancy CgA levels in maternal and umbilical cord plasma and in amniotic fluid at term (39-40 weeks), by enzyme-linked immunosorbent assay at elective cesarean (n = 16), after spontaneous vaginal delivery (n = 12), and longitudinally throughout labor and 2 hours postpartum. RESULTS: CgA levels were highest in umbilical cord blood (P <.001). Umbilical cord plasma and amniotic fluid CgA levels were significantly higher at spontaneous vaginal delivery than at cesarean (P <.001), and the levels were not changed in maternal plasma according to cervical dilatation and postpartum. CONCLUSIONS: The present findings showed that the stress of parturition increased CgA levels in umbilical cord plasma and amniotic fluid and was probably of fetal origin. Whatever the mode of delivery, CgA levels in infants were much more elevated than in mothers, providing evidence for an unusual and sustained high level of sympathoadrenal stimulation in full-term neonates.

Adult↗