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Biomedical subjects

M Bobbio

Publications and source records attributed to M Bobbio.

At least 19 recordsLinked to original sources

Growth hormone-independent cardiotropic activities of growth hormone-releasing peptides in normal subjects, in patients with growth hormone deficiency, and in patients with idiopathic or ischemic dilated cardiomyopathy.

Growth hormone releasing peptides (GHRPs) are synthetic molecules endowed with potent neuroendocrine activities mediated by specific receptors in the pituitary and in the central nervous system. GHRPs receptors have been reported even in perpheral tissues, particularly in the myocardium, where they probably mediate growth hormone (GH)-independent activities. We studied in humans the cardiac effects of hexarelin administration in 7 normal adults, in 7 severe GH-deficient patients, and in 12 patients with severe dilated cardiomyopathy. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP), heart rate (HR), and GH levels were evaluated at baseline and every 15 min up to 60 min after acute 2.0 microg/kg iv hexarelin administration. Basal LVEF in dilated cardiomyopathy was impaired and lower (p < 0.001) than in GH deficiency, in turn lower (p< 0.001) than in normal subjects. Hexarelin signficantly (p < 0.05) increased LVEF in normal and in GH-deficient subjects, but not in dilated cardiomyopathy, without significant variations in MBP and HR. Hexeralin significantly (p < 0.05) increased GH levels in normal subjects and in dilated cardiomyopathy but not in GH deficiency. These findings suggest that, in humans, the acute administration of hexarelin exerts a GH-independent positive inotropic effect likely mediated by specific GHRPs myocardial receptors.

Adult↗

[The new limitations of the Italian Regulatory Agency on Drugs].

In Italy the reimbursement of few free-of-charge drugs is limited to subgroups of patients or to one of the approved indications. In February 2001 new rules will become mandatory for Italian physicians. The text of the new rules related to drugs mostly used by cardiologists (levocarnitine, ticlopidine, hypolipemic drugs) is reported.

Heart Diseases↗

Normal IGF-I and enhanced IGFBP-3 response to very low rhGH dose in patients with dilated cardiomyopathy.

Well-nourished patients with dilated cardiomyopathy (DCM) show slight reduction of mean basal IGF-I levels which, however, display a response to a rhGH dose as low as 5.0 microg/kg/day similar to that of age-matched control subjects (CS). To further investigate peripheral GH sensitivity, we studied the IGF-I and IGFBP-3 responses to 4-day s.c. 2.5 microg/kg/day rhGH administration, the lowest effective dose able to increase IGF-I levels in normal subjects, in 10 DCM patients [age (mean+/-SE): 57.6+/-1.0 yr, body mass index (BMI): 24.0+/-1.2 kg/m2, left ventricular ejection fraction: 26.2+/-3.2%, NYHA (New York Heart Association): I/0, II/4, III/4, IV/2] and in 9 age-matched healthy CS (age: 55.3+/-1.2 yr, BMI: 23.7+/-1.8 kg/m2). Basal IGF-I levels in DCM were lower though not significantly than those in CS (147.7+/-9.8 vs 174.7+/-17.0 microg/l). Basal IGFBP-3 levels in DCM were similar to those in CS (3.1+/-0.3 vs 2.7+/-0.2 mg/l). In CS 4-day rhGH increased IGF-I levels (222.4+/-14.9 microg/l; p<0.01 vs baseline) but did not modify IGFBP-3 levels (3.0+/-0.2 mg/l). In DCM IGF-I levels were increased by 4-day rhGH administration (175.7+/-11.0 microg/l; p<0.05 vs baseline) with a similar percent extent than in CS. On the other hand, in DCM, but not in CS, 4-day rhGH significantly increased IGFBP-3 levels (3.5+/-0.3 mg/l; p<0.05 vs baseline). Therefore, in conclusion, testing with the lowest effective rhGH dose further suggest that peripheral GH sensitivity in well-nourished DCM is preserved. On the other hand, DCM patients show enhanced IGFBP-3 sensitivity to stimulation by rhGH.

Cardiomyopathy, Dilated↗

Patients with dilated cardiomyopathy show reduction of the somatotroph responsiveness to GHRH both alone and combined with arginine.

OBJECTIVE: Altered function of the GH/IGF-I axis in patients with dilated cardiomyopathy (DCM) has been reported. In fact, DCM patients show reduction of IGF-I levels, which could reflect slight peripheral GH resistance or, alternatively, reduced somatotroph secretion. Spontaneous GH secretion has been reported to be altered by some but not by other authors, whereas the GH response to GHRH, but not that to GH-releasing peptides, seems reduced in DCM patients. On the other hand, it is well known that the GH response to GHRH in humans is markedly potentiated by arginine (ARG), which probably acts via inhibition of hypothalamic somatostatin release; in fact the GHRH+ARG test is known as one of the most reliable to evaluate the maximal secretory capacity of somatotroph cells. METHODS: In order to further clarify the somatotroph function in DCM, in well-nourished patients with DCM (34 male, 4 female; age (mean+/-s.e. m.) 57.8+/-1.1 years; body mass index (BMI) 24.6+/-0.6kg/m(2); left ventricular ejection fraction 23.2+/-1.6%; New York Heart Association classification I/1, II/17, III/18, IV/2) we studied the GH response to GHRH (1.0 microgram/kg i.v.) alone or combined with ARG (0.5g/kg i.v.). The results in DCM patients were compared with those in age-matched control subjects (CS) (39 male, 7 female; age 58.9+/-1.0 years; BMI 23.2+/-0.3kg/m(2)). RESULTS: Mean IGF-I levels in DCM patients were lower than in CS (144.3+/-6.9 vs 175.1+/-8. 4 microgram/l, P<0.05) whereas basal GH levels were similar in both groups (1.7+/-0.3 vs 1.7+/-0.3 microgram/l). The GH response to GHRH in DCM patients was lower (P<0.05) than that in CS (GH peak 6.5+/-1.2 vs 10.7+/-2.1 microgram/l). In both groups the GH response to GHRH+ARG was higher (P<0.001) than that to GHRH alone. However, the GH response to GHRH+ARG in DCM patients remained clearly lower (P<0.01) than that in CS (18.3+/-3.2 vs 34.1+/-4.6 microgram/l). The GH response to GHRH alone and combined with ARG was not associated with the severity of the disease. CONCLUSION: DCM patients show blunted GH responses to GHRH both alone and combined with ARG. Evidence that ARG does not restore the GH response to GHRH in DCM patients makes it unlikely that the somatotroph hyporesponsiveness to the neurohormone reflects hyperactivity of hypothalamic somatostatinergic neurons.

Arginine↗

[Surrogate end points].

In order to evaluate the efficacy of a treatment, "minor" end points (the reduction in serum cholesterol, blood pressure, serum creatinine) that have a pathophysiological or statistical relationship with the true end points (reduction in mortality, incidence of myocardial infarction, or surgical procedures) are often adopted. They are called surrogate end points because they are used instead of true end points. In cardiology the results of clinical trials with clofibrate, milrinone, flecainide and more recently with doxazosine have demonstrated that the reduction of a surrogate end point does not correspond to the reduction of mortality. To define a treatment for a patient, clinicians should distinguish surrogate from true end points choosing evidence-based treatments and avoiding those that are supported only by pathophysiological assumptions.

Evidence-Based Medicine↗

[The SET-UP study].

Explore the source record for details and available documents.

Clinical Trials as Topic↗

[Cardiologists and limitations of statins reimbursement].

BACKGROUND: In Italy of five approved HMG-CoA reductase inhibitors (atorvastatin, cerivastatin, fluvastatin, pravastatin, and simvastatin) only the last two are reimbursed by the National Health System for secondary prevention of coronary artery disease. METHODS: During the 1999 Annual Meeting of the National Association of Hospital Cardiologists (ANMCO) a questionnaire was included in the meeting material. The aim was two-fold: 1) to evaluate whether Italian cardiologists approve the National Health System policy to reimburse only pravastatin and simvastatin for secondary prevention, and 2) to assess which end-points are considered sufficient to grant the reimbursement of additional HMG-CoA reductase inhibitors. RESULTS: Two hundred and thirty-two completed questionnaires were collected and analyzed: 90.1% (95% confidence interval-CI between 85.1 and 93.6%) of cardiologists agree that only HMG-CoA reductase inhibitors with evidence-based mortality reduction should be reimbursed in Italy for secondary prevention; 75.0% (95% CI between 69.4 and 80.6%) follow the State guidelines in order to choose the approved HMG-CoA reductase inhibitors and 69.4% (95% CI between 63.5 and 75.3%) judge that at least the demonstration of coronary artery plaque reduction should be considered as an evidence-based decision to include new HMG-CoA reductase inhibitors for reimbursement. CONCLUSIONS: Most of Italian cardiologists who answered the questionnaire agreed with the limitation of reimbursement to only HMG-CoA reductase inhibitors with evidence-based demonstration of mortality reduction and asserted that the only reduction in blood cholesterol levels should not be considered proof of efficacy.

Adult↗

Cholesterol and long-term mortality after acute myocardial infarction in elderly patients.

METHOD: We investigated the association of total serum cholesterol concentrations and subsequent overall and coronary mortality in 304 patients aged > or =65 discharged from hospital after acute myocardial infarction. RESULTS: There was no association between total cholesterol concentrations and mortality due to either coronary heart disease or to all causes in all patients or, separately, in men, women, patients younger than 75 and patients aged 75 years and older.

Aged↗

Peak exercise oxygen consumption in chronic heart failure: toward efficient use in the individual patient.

OBJECTIVES: This study sought to 1) assess the short-, medium-and long-term prognostic power of peak oxygen consumption (VO2) in patients with heart failure; 2) verify the consistency of a nonmeasurable anaerobic threshold (AT) as a criterion of nonapplicability of peak VO2; 3) develop simple rules for the efficient use of peak VO2 in individualized prognostic stratification and clinical decision making. BACKGROUND: Peak VO2, when AT is identified, is among the indicators for heart transplant eligibility. However, in clinical practice the application of defined peak VO2 cutoff values to all patients could be inappropriate and misleading. METHODS: Six hundred fifty-three patients consecutively considered for eligibility for heart transplantation were followed up. Outcomes (cardiac death and urgent transplantation) were determined when all survivors had a minimum of 6 months of follow-up. RESULTS: Contraindication to the exercise test identified very high risk patients. The relatively small sample of women did not allow inferences to be drawn. In men, peak VO2 stratified into three levels (< or = 10, 10 to 18 and >18 ml/kg per min) identified groups at high, medium and low risk, respectively. The prognostic power of peak VO2 < or = 10 ml/kg per min was maintained even when the AT was not detected. In patients in New York Heart Association functional class III or IV, peak VO2 did not have prognostic power. In patients in functional class I or II, peak VO2 stratification was prognostically valuable, but less so at 6 than at 12 or 24 months. Age did not influence peak VO2 prognostic stratification. CONCLUSIONS: A contraindication to exercise testing should be considered a priority for listing patients for heart transplantation. Only in less symptomatic male patients does a peak VO2 < or = 10 ml/kg per min identify short-, medium- and long-term high risk groups. A peak VO2 >18 ml/kg per min implies good prognosis with medical therapy.

Anaerobic Threshold↗

Administration of thrombolytic therapy to 17,944 patients with acute myocardial infarction: the GISSI-3 database.

BACKGROUND: There is growing interest in assessing therapy for acute myocardial infarction. Because thrombolysis was not a study therapy in the GISSI-3 trial, the decision about thrombolysis was left to the responsible physicians. We evaluated the data on thrombolytic therapy among patients with acute myocardial infarction enrolled in the GISSI-3 trial to study the relation between rate of prescription and the characteristics of patients and participating coronary care units. METHODS: Complete clinical data were available for 17,944 patients randomized between June 1991 and July 1993 from 200 coronary care units in Italy. Demographic and clinical information were obtained for each patient, and each coronary care unit was classified according to patient volume, level of technology, and wide geographic area in which it was located. A multivariate logistic regression was performed with administration of thrombolytic therapy as the dependent variable and previously defined clinical and structural variables as independent variables. RESULTS: The most important factor in administration of thrombolytic therapy was that less than 6 hours elapse from symptom onset to hospital admission (odds ratio [OR] 14.05; 95% confidence interval [CI] 12.3 to 16.0). Next were location of coronary care unit in southern Italy (OR 1.81; 95% CI 1.62 to 2.01), presence of ST elevation at entrance electrocardiogram ECG (OR 1.47; 95% CI 1.35 to 1.61), absence of previous myocardial infarction (OR 1.35; 95% CI 1.22 to 1.49), and presence of catheterization laboratory or cardiac surgery program or both in the same hospital (OR 1.24; 95% CI 1.14 to 1.35). Coronary care units with high or low patient volume did not show different rates of administration of thrombolytic agents. CONCLUSIONS: The GISSI-3 experience confirmed a high rate of prescription of thrombolytic therapy to patients admitted within 6 hours of symptom onset and those with ST-segment elevation on entrance electrocardiogram. It demonstrated that patients admitted to coronary care units with catheterization laboratories or cardiac programs or both have higher chances of receiving thrombolytic treatment than those admitted to hospitals without these capabilities.

Adult↗

Myocardial revascularization through a mini-thoracotomy with thoracoscopic assistance.

OBJECTIVE: Left internal mammary artery harvesting through a mini-thoracotomy makes gaining the proximal portion of this vessel very difficult and exposes the patient to the risk of chest wall trauma due to excessive spreading of the ribs. The adoption of video thoracoscopic assistance can give several advantages to the procedure. METHODS: With the patient in a 30 degrees left-side-up thoracotomy position, a 8-12 cm anterior thoracotomy is performed in the left fourth or fifth intercostal space. Two thoracoscopic ports are inserted in the third and fourth left intercostal spaces in the midaxillary line. Complete mobilization of the left internal mammary artery is performed with a mixed surgical and thoracoscopic technique. RESULTS: Since July 1996, 12 patients underwent myocardial revascularization with the left internal mammary artery through a mini-thoracotomy, with the aid of video assisted thoracoscopy. There were no deaths or perioperative infarctions. Mean hospital stay was 4 days (3-6). In nine patients a postoperative angiographic study was performed: in all cases the length of the mammary artery pedicle was adequate; one patient underwent a successful angioplasty on a narrowed anastomosis on the left anterior descending artery. In another patient the left internal mammary artery had been grafted to a diagonal branch. In all other cases angiography showed good results. CONCLUSIONS: Thoracoscopic assistance helps achieving complete mobilization of the left internal mammary artery, maximizing its useful length, without an extended thoracotomy.

Endoscopy↗

Clinical and epidemiological characteristics of juvenile myocardial infarction in Italy: the GISSI experience.

BACKGROUND: No clinical and epidemiological data are available about acute myocardial infarction (AMI) at a young age in large populations, due to the low prevalence of AMI in younger people. The aim of the present study is to analyze epidemiological and clinical characteristics of AMI among younger people in Italy, using the data bases of the three GISSI studies. METHODS: Analysis of epidemiological and clinical characteristics of AMI according to different age groups in the three GISSI studies that collected data from 1985 to 1993. RESULTS: In the GISSI-2 and GISSI-3 data bases, the prevalence of AMI at a young age (2 and 1.8% respectively; difference -0.2% with 95% CI from -0.4 to 0.3%), hospital mortality (2.3 and 1.9% respectively; difference -0.4% with 95% CI from -1.9 to 1.0%), and the rate of young female patients (8 and 7% respectively; difference -1% with 95% CI from -3.6 to 1.6%) are similar. In the GISSI-2 study, we observed that in comparison to elderly patients (> 70 years) young patients (< 40 years) are more frequently smokers (83.9 vs 21.0%; difference 62.9% with 95% CI from 58.5 to 67.3%) and have a higher rate of family history for CAD (42.1 vs 21.1%; difference 21.0% with 95% CI from 15.3 to 26.7%) and of hypercholesterolemia (28.3 vs 15.0%; difference 13.3% with 95% CI from 18.5 to 80.8%), but show a lower prevalence of hypertension (12.2 vs 44.3%; difference from -32.1% with 95% CI from -28.0 to -36.2%) and diabetes (2.9 vs 18.8%; difference -15.9% with 95% CI from -13.5 to -18.3%). AMI at a young age is generally the first event in ischemic heart disease; in comparison with older patients with previous AMI (6.4 vs 17.4%; difference -11.0% with 95% CI from -7.8 to -14.0%) and history of angina (23.2 vs 40.0%, difference -16.8% with 95% CI from -11.8 to -21.9%) this is less frequent. The rate of complications is lower in younger as opposed to older patients for both early (7.7 vs 31.2%; difference -23.5% with 95% CI from -20.0 to -26.9%) and late heart failure (2.9 vs 18.5%; difference -15.6% with 95% CI from -13.2 to -18.0%), as well as for angina (6.4 vs 10.5%; difference -4.1% with 95% CI from -1.1 to -7.1%), reinfarction (1.0 vs 3.3%; difference -2.3% with 95% Ci from -1.1 to -3.6%) and complete AV block (1.6 vs 6.6%; difference -5.0% with 95% CI from -3.3 to -6.7%). In young patients, we observed lower in-hospital (1.6 vs 21.1%; difference -19.5% with 95% CI to -21.6%) and six-month mortality (1.3 vs 8.1%; difference -6.8% with 95% CI from -5.0 to -8.5%). CONCLUSIONS: The incidence and mortality of AMI at a young age was steady during the period between 1988 and 1993. AMI at a young age is a clinical entity with specific characteristics that differ from those found in old patients. In addition, it has peculiar risk profile with a better short- and medium-term outcome.

Adult↗

[Models of preoperative risk stratification in cardiac surgery: the prediction of mortality or of survival?].

BACKGROUND: The need to assess the quality of heart surgery outcomes stimulated the development of pre-surgical risk stratification models in order to predict outcome on the basis of patient characteristics. The aim of the study was to compare the predictive accuracy of hospital mortality according to the following three models: Parsonnet (NBI Score), Higgins (CCF Score) and Roques (French Score), in a setting totally independent from the one in which the models were derived. METHODS: For each of the 516 patients undergoing heart surgery at our institution between January 1992 and December 1993, we calculated the pre-surgical risk according to the three models. Then we compared the predicted mortality against the observed mortality by means of the Shannon accuracy index, the ROC curve analysis and the overestimation histogram. RESULTS: Overall observed mortality (1.5%) was similar to the predicted mortality by the NBI Score (1.5 +/- 2.1%, p = ns), the CCF Score (1.7 +/- 2.0%, p = ns) and the French Score (1.9 +/- 2.5%, p = ns). The predictive accuracy of global mortality is very high and equal with the three models, and it is very low in the 8 patients who died (NBI Score = 0.06 +/- 0.06; CCF Score = 0.125 +/- 0.067; French Score = 0.102 +/- 0.07, p = ns). The area under the ROC curve is identical in the 3 models. CONCLUSIONS: The predicted mortality obtained by the three models is not significantly different from the observed mortality and therefore, the global accuracy is similar and very high, while it is very low for patients who will die. The models for pre-surgical risk stratification are useful for comparing the results among different institutions or different surgeons, or for monitoring the results over time in the same institution, but they cannot be used to accurately predict the individual risk of hospital mortality.

Aged↗