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Biomedical subjects

Roberto Delsignore

Publications and source records attributed to Roberto Delsignore.

15 recordsLinked to original sources

Endothelial dysfunction and cardiovascular risk profile in long-term withdrawing alcoholics.

BACKGROUND: Rates of cardiovascular morbidity and mortality are greater in heavy alcoholics than in either teetotallers or light-to-moderate drinkers. OBJECTIVE: On the assumption that factors leading to atherosclerotic damage remain operative even after long-term alcohol withdrawal, we studied the possible mechanisms of raised cardiovascular risk in former heavy alcoholics. METHODS: Forty-two apparently disease-free, normotensive alcoholics detoxified for 37.1 +/- 31.9 (SD) months, median 24, participated in the study. They were compared with 39 lifetime alcohol-abstaining control subjects, carefully matched for age, sex, body mass index, smoking and dietary habits, physical activity, lipids and fasting glucose. Endothelial function (flow-mediated dilation of brachial artery, high-resolution ultrasound technique), blood pressure, and some parameters of endothelial activation, oxidative stress, vascular inflammation and insulin sensitivity were measured. RESULTS: The maximal percentage of flow-mediated dilatation was reduced in detoxified alcoholics (10.1 +/- 4.6 versus 14.9 +/- 7.4, P < 0.001) who also showed significantly higher blood pressure (systolic 127.5 +/- 12.9 versus 118.2 +/- 10.7 mmHg, P < 0.001; diastolic 79.4 +/- 7.1 versus 74.6 +/- 6.4 mmHg, P < 0.01; mean 95.4 +/- 8.2 versus 89.1 +/- 7.3 mmHg, P < 0.001), uric acid (5.0 +/- 1.1 versus 4.4 +/- 0.8 mg/dl, P < 0.05), high-sensitivity C-reactive protein (2.1 +/- 2.0 versus 1.0 +/- 0.9 mg/l, P < 0.01), endothelin-1 (0.38 +/- 0.11 versus 0.17 +/- 0.10 pg/ml, P < 0.001) and fasting insulin (10.4 +/- 4.5 versus 5.6 +/- 1.6 muU/ml, P < 0.001) with abnormal homeostasis model assessment index of insulin resistance (2.3 +/- 1.1 versus 1.2 +/- 0.4, P < 0.001). CONCLUSION: Previous heavy alcoholism, in spite of long-term withdrawal, is associated with endothelial dysfunction and a wide cluster of haemodynamic, vascular and metabolic abnormalities that indicate an unfavourable cardiovascular and metabolic risk profile even in apparently disease-free former alcoholics.

Adult↗

Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy.

BACKGROUND: In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension. This observational study was designed to evaluate the prevalence of pulmonary hypertension in hyperthyroidism and to determine the role of methimazole in regulating pulmonary vascular resistance in these patients. METHODS: We studied 114 patients, 78 women and 36 men, whose mean age was 51+/-13years. Forty-seven had Graves' disease and 67 had a nodular goiter. All subjects were ambulatory and were recruited in a consecutive order. The control group (group 2) included 20 healthy subjects matched for age and sex. Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressure (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli's equation. We performed a 120-day follow-up in the patients with pulmonary hypertension and we divided them into two subgroups: group 1A (n=33), patients treated with methimazole, and group 1B (n=17), subjects treated with partial thyroidectomy. RESULTS: We found a mild pulmonary hypertension in 50 patients in group 1 (43%) and in none of those in the control group. The mean+/-SD PAPs was 27.77+/-6.56 in group 1 and 21.32+/-2.55 in group 2. A negative correlation was found between the T.S.H. value and the level of PAPs (r=-0.85; p<0.001). During the follow-up, group 1A went from a PAPs value of 34.3+/-3.2 to 29.2+/-3.3 after 15days of therapy and group 1B from 34.3+/-3.0 to 34.1+/-2.9 (p<0.001). CONCLUSIONS: The results of the present study demonstrate a frequent association between hyperthyroidism and mild and transient pulmonary hypertension. Subjects treated with methimazole have a more rapid drop in PAPs.

Journal Article↗

Clinical management of paroxysmal nocturnal hemoglobinuria in pregnancy: a case report and updated review.

UNLABELLED: Because women with paroxysmal nocturnal hemoglobinuria (PNH) are especially vulnerable to thromboembolic phenomena, pregnancy is a time of increased risk for both mother and fetus. However, pregnancies in affected women are rare; only case reports and small studies have been reported so far. We present the case of a 20-year-old woman with PNH who, while undergoing medical tests in preparation for a bone marrow transplant, was discovered to be pregnant. We also review the obstetric literature on pregnancy complicated by PNH, which indicates that both maternal and fetal mortality is exceptionally high (11.6% and 7.2%) with the major cause of maternal mortality being thromboembolism. Major maternal complications are more frequent postpartum (30.2%) than antepartum or intrapartum (16.3%). TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that paroxysmal nocturnal hemoglobinuria (PNH) during pregnancy increases adverse events for both the mother and the fetus, state that maternal and fetal mortality are both high, and explain that the major complications occur in the postpartum period.

Adult↗

Is steroid therapy needed in the treatment of destructive thyrotoxicosis induced by alpha-interferon in chronic hepatitis C?

OBJECTIVE: Treatment with interferon (IFN) of patients affected by chronic hepatitis C (CH-C) may produce alterations in thyroid function, such as hypothyroidism, Graves'-like hyperthyroidism and destructive thyrotoxicosis (DT). IFN-induced DT is characterized by suppressed serum TSH levels, normal or elevated FT4 and FT3 concentrations, with the presence or absence of thyroid peroxidase antibodies and antithyroglobulin antibodies, the absence of thyroid receptor antibodies and radioactive iodine uptake suppressed or <5%. DESIGN: IFN-induced DT is a mild clinical disease, because thyroid-destructive processes last for a short time and involve a small portion of the gland. At present, the therapeutic approach in DT suggests IFN withdrawal and 1-2 months of methylprednisolone treatment. METHODS: In consideration of possible untoward side effects of steroid treatment in patients with CH-C, we studied two groups of patients with CH-C who developed DT after treatments with various preparations of recombinant IFN (with or without ribavirin). Patients sequentially entered the study during a 4-year period, at the time of DT diagnosis, when IFN therapy was discontinued. The first 12 subjects (group A) were treated with 8-16 mg/day methylprednisolone for 30-40 days after IFN withdrawal; in the following 15 patients (group B), IFN withdrawal was not followed by any additional treatment. All patients underwent clinical and laboratory controls of thyroid function at 1, 2, 3 and 6 months after DT diagnosis. RESULTS: The results showed restoration of euthyroidism in both group A and group B patients at 6 months after DT diagnosis, regardless of steroid treatment. CONCLUSIONS: The simple withdrawal of IFN therapy in patients with CH-C, who had developed DT, appears to be effective in the treatment of the thyroid disease. This therapeutic approach should be preferred in order to avoid possible undesired side effects of steroid therapy in patients with CH-C.

Adult↗

Hyperinsulinemia predicts hepatic fat content in healthy individuals with normal transaminase concentrations.

Although the prevalence of insulin resistance (IR) and compensatory hyperinsulinemia (CH) is increased in patients with nonalcoholic fatty liver disease, the role of IR/CH in regulation of hepatic fat content in healthy volunteers with normal concentrations of alanine transaminase (ALT) has not been defined. To address this issue, hepatic fat content was quantified by ultrasound in 69 (30 men, 39 women) healthy individuals, without known risk factors for liver disease and with plasma ALT concentrations of less than 30 U/L. Experimental variables quantified included body mass index, waist circumference, systolic and diastolic blood pressures, and fasting plasma glucose, fasting plasma insulin (FPI), and lipid concentrations. Subjects were classified as having no (55%), mild (27%), or moderate to severe (18%) hepatic steatosis on the basis of the ultrasound results. Statistically significant (P < .05-.001) correlations (Spearman rho values) existed between liver fat content and ALT (0.26), body mass index (0.52), waist circumference (0.50), systolic blood pressure (0.28), diastolic blood pressure (0.27), fasting plasma glucose (0.47), FPI (0.56), triglycerides (0.30), and high-density lipoprotein cholesterol (-0.35). Multivariate general discriminant analysis and multiple linear regression analysis indicated that FPI was the only independent predictor (P < .001) of both liver fat content and ALT concentrations. Fasting plasma insulin (a surrogate estimate of IR/CH) predicts hepatic fat content and ALT in healthy volunteers with normal transaminase concentrations, independently of the other anthropometric and metabolic variables measured.

Aged↗

Graves' disease in interferon-alpha-treated and untreated patients with chronic hepatitis C virus infection.

An association between Graves' disease (GD) and chronic hepatitis C (C-HC) has been observed both in the presence and the absence of recombinant interferon-alpha (rIFN-alpha) treatment. rIFN-alpha-induced GD is characterized by suppressed thyroid-stimulating hormone levels; normal or elevated free triiodothyronine (FT3) and free thyroxine (FT4) values; the presence of thyroid peroxidase antibodies, antithyroglobulin antibodies, and thyroid receptor antibodies; and high iodine thyroid uptake. In contrast, GD developed during C-HC without rIFN-alpha is less clearly defined. In this study, we examined two groups of patients: group A, 28 patients with C-HC treated with rIFN-alpha who developed GD after 1 to 9 months, and group B, 10 patients with C-HC who developed GD without a previous rIFN-alpha treatment. At the time of GD, both groups started methimazole therapy; thyroid function was reevaluated after 3, 6, 9, and 12 months. Group A patients continued IFN. After 12 months, all patients of group A were euthyroid, and 21 of them (75%) had already stopped methimazole treatment, whereas all patients of group B were euthyroid and only 2 (20%) had stopped methimazole. In conclusion, the data show a better course of GD, with a more precocious and significantly higher number of recoveries in patients with rIFN-alpha-induced GD than in rIFN-alpha-unrelated disease. Further studies are needed to establish whether the two types of GD differ not only from a clinical point of view but also because of different underlying pathogenetic mechanisms.

Antiviral Agents↗

Pulmonary complications in diabetes mellitus: the role of glycemic control.

Insulin deficiency induces an increase in blood glucose levels that, in long run, becomes toxic for many organs and systems. Microangiopathy and derangements in the immune function are known consequences of hyperglycemia, but the way in which these systemic alterations may affect pulmonary function has been scarcely investigated. Although confirmation from large clinical trials is still to come, the diabetic disease seems to hit the pulmonary microcirculation as any other organ by increasing vessel wall thickness and impairing gas exchange, which leads to a measurable loss of function and respiratory efficiency. In addition, a diabetic lung is more susceptible to low respiratory tract infections by atypical microorganisms and more likely to host severe episodes of pneumonia than a normal, non-diabetic lung. This is a review of current knowledge on the impact of diabetes mellitus in lung health. We have paid special attention to the role of metabolic control in preventing damage to the lung by sustained hyperglycemia.

Diabetes Complications↗

[Thyroid dysfunction and pulmonary hypertension].

Prior observational studies and several case reports have suggested an association between thyroid dysfunction and pulmonary hypertension. This review was designed to evaluate the prevalence and the pattern of pulmonary vasculature involvement in hyper- and hypothyroidism. We identified original research papers and reviews by going through leading journals that publish basic and clinical research in the fields of pulmonary hypertension, hyperthyroidism and hypothyroidism, by electronically searching the Medline database. We directed special attention to papers published from 1972 to 2003. Our findings indicate the presence of a frequent association between hyperthyroidism and pulmonary hypertension (35% in the largest series of cases) which decrease after achievement of a euthyroid state. A possible explanation includes an influence of thyroid hormones which affect growth and maturation of vascular cells and enhanced catecholamine sensitivity causing pulmonary vasoconstriction. Furthermore, several studies suggest a high prevalence of transient pulmonary hypertension in hypothyroidism (49% in the largest series of cases), in these cases autoimmunity play a key role.

Animals↗

Low vitamin D status, high bone turnover, and bone fractures in centenarians.

The oldest olds, including centenarians, are increasing worldwide and, in the near future, will represent a consistent part of the population. We have studied bone status and metabolism in 104 subjects over 98 yr of age to evaluate possible interventions able to avoid fragility fractures and disability. Ninety females and 14 males not affected by any acute disease were considered. After a complete clinical assessment, blood was drawn for evaluating bone turnover markers, and performance tests together with skeletal ultrasonography (either at the phalanges or at the heel) were performed. We found that 38 subjects had sustained a total of 55 fractures throughout their lives, and 75% of these were fragility fractures. Twenty-eight fractures occurred at the proximal femur, with 14 after the age of 94 yr. Serum 25-hydroxyvitamin D was undetectable in 99 of 104 centenarians. PTH and serum C-terminal fragment of collagen type I were elevated in 64 and 90% of centenarians, respectively, with a trend toward hypocalcemia. Bone alkaline phosphatase levels were close to the upper limit. Serum IL-6 was elevated in 81% of centenarians and was positively correlated with PTH and negatively correlated with serum calcium. Serum creatinine was not correlated with PTH. Bone ultrasonography showed that most centenarians had low values, and ultrasonographic parameters were correlated with resorption markers. We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.

Activities of Daily Living↗

Effects of (+/-) 3,4-methylene-dioxymethamphetamine (ecstasy) on dopamine system function in humans.

Twelve (+/-) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse (group A), and 12 control subjects (group B) were included in the study. Prolactin (PRL) and growth hormone (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in A and B subjects after BROM suppression, without any significant difference between the two groups. PRL responses to BROM in MDMA users were in the normal range. In contrast, GH responses to BROM stimulation were found significantly reduced in ecstasy users, in comparison with control subjects (P < 0.001; F = 6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs) showed a significant inverse correlation with NS scores both in A and B subjects. GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA users. No other psychometric measure correlated with hormonal responses. GH AUCs were inversely correlated with the measures of MDMA exposure (r = -0.48; P < 0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced D2 receptor sensitivity in the hypothalamus, possibly due to increased intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic changes associated with a premorbid condition cannot be completely excluded, the inverse correlation between DA receptors sensitivity and the extent of ecstasy exposure may suggest a direct pharmacological action of MDMA on brain dopamine function in humans.

Adolescent↗

Do coronary heart disease risk factors change over time?

The stability over a 12-year period of several coronary heart disease (CHD) risk factors was evaluated in 348 individuals who had remained healthy following baseline measurements made of the same variables in 1981. CHD risk factors evaluated were fasting and post-glucose challenge (120-minute) plasma glucose and insulin concentrations, plasma triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) concentrations, and the ratio of LDL/HDL cholesterol concentrations. Approximately 40% to 60% of individuals in the highest CHD risk quartile (or lowest in the case of HDL cholesterol concentrations) in 1981 were still at highest risk in 1993. A similar proportion of individuals at lowest risk in 1981 were still in that category in 1993. At least 50% of the participants in this prospective analysis experienced a change by 1 quartile or more in each of the metabolic CHD risk factors measured, and these differences were highly statistically significant for all variables measured with the exception of the TG and HDL cholesterol concentrations. These results demonstrate that the implicit assumption in epidemiological studies that CHD risk factors at baseline remain stable may require examination.

Blood Glucose↗

Sodium sensitivity as a main determinant of blood pressure changes during early withdrawal in heavy alcoholics.

BACKGROUND: Stimulated sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, and cortisol are thought to affect blood pressure in early withdrawal of alcoholics. Hyperactivity of sodium-retaining systems with consequent volume expansion also could interact with sodium sensitivity as previously found in long-term withdrawing alcoholics. METHODS: To investigate this hypothesis, blood pressure and sodium balance were measured during the first 8 days of withdrawal in 18 chronic alcoholics on a 150 mM Na diet. Results were related to the Salt Sensitivity Index of blood pressure as measured in the same alcoholics after 1 year of abstinence. RESULTS: Early withdrawal study: there was a positive sodium balance (+288.6 +/- 45.6 mM; p < 0.0001) and rise in mean arterial pressure (+11.8 +/- 2.9 mm Hg; p = 0.001) during early withdrawal on 150 mM Na diet. Salt Sensitivity Study after long-term detoxification: the shift from low (55 mM) to high sodium (260 mM) intake produced a larger (p = 0.04) increase in mean arterial pressure in alcoholics (+9.3 +/- 2.0 mm Hg) than in 30 teetotal controls (+5.1 +/- 1.1) (Salt Sensitivity Index, 0.047 +/- 0.008 vs. 0.023 +/- 0.0053; p < 0.05). Changes in mean blood pressure during withdrawal were highly related to sodium sensitivity index (r = 0.8; p < 0.001). CONCLUSIONS: Early withdrawing alcoholics exposed to a normal sodium intake experience positive Na balance and increase in blood pressure that is related to sodium sensitivity measured after long-term detoxification. This suggests that salt sensitivity plays a key role in blood pressure regulation in early withdrawing alcoholics.

Adult↗

Acute antiarrhythmic effects of bi-level positive airway pressure ventilation in patients with acute respiratory failure caused by chronic obstructive pulmonary disease: a randomized clinical trial.

BACKGROUND: Cardiac arrhythmias are common in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure (ARF) and may be life threatening. Recently, non-invasive positive pressure ventilation has been advanced as a useful tool in COPD patients with ARF. This method can affect global cardiac performance through its effects on many determinants of cardiac function and may be helpful in reducing arrhythmias. OBJECTIVE: To assess the role of bi-level positive pressure ventilation (BiPAP) in the management of cardiac arrhythmias in patients with ARF caused by COPD. METHODS: We studied 30 consecutive patients with ARF related to COPD diagnosed according to American Thoracic Society criteria. All subjects were smokers; the mean age was 68 +/- 7 years. They were randomly assigned to receive BiPAP plus standard therapy (group 1) or standard therapy alone (group 2). Patients randomized to receive BiPAP were first fitted with a nasal mask, and BiPAP was administered after 12 h of standard therapy. All subjects were studied using a computerized 24-hour Holter ECG. Blood gases, plasma electrolytes, respiratory rate and blood pressure were measured at study entry, at 30, 60 and 120 min and then every 3 h. RESULTS: Heart rate decreased from 86.08 +/- 7.86 to 74.92 +/- 5.39 in group 1 (p < 0.001) versus 82.77 +/- 8.78 to 75.82 +/- 6.76 in group 2 (p = 0.033). Ventricular premature complexes decreased from 564.38 +/- 737.36 to 166.15 +/- 266.26 in group 1 (p < 0.001) versus 523.38 +/- 685.75 to 353.54 +/- 469.93 in group 2 (p = 0.021). Atrial premature complexes decreased from 570.00 +/- 630.36 to 152.31 +/- 168.88 in group 1 (p < 0.001) versus 513.77 +/- 553.81 to 328.62 +/- 400.81 in group 2 (p = 0.021). CONCLUSIONS: Cardiac arrhythmias decreased significantly in both groups after the start of both treatments, although data obtained from group 1 revealed a more important statistical significance. Our data seem to support the hypothesis that BiPAP may be a useful tool in managing COPD patients with ARF and mild arrhythmias.

Acute Disease↗

Red cell Hb oxidation of healthy subjects compared to breast cancer patients.

The end result of our research would be the development of a new diagnostic technique that could be used as a screening test, starting from a simple blood collection, a common procedure without any risk to the subject. Red blood cells (RBC) of patients affected by breast cancer are more sensitive to the denaturing action of acetylphenylhydrazine (APH), hence the formation time of hemin, one of the last oxidation products, is significantly shorter then in normal subjects. Our previous experiment showed the differences during iron oxidation between breast cancer patients and healthy persons (Croci et al. 2001). Different amounts of hemin, after the same incubation time, can discriminate between samples collected from people suffering from cancer and a healthy population. These results have given birth to the necessity to standardise a procedure useful as a screening method. The aim of the present work was to define a range of values that characterise the samples collected from healthy people.

Breast Neoplasms↗

Association between immune thrombocytopenic purpura and chronic lymphocytic leukemia in a patient carrier of anti-hepatitis C virus antibodies.

Immune thrombocytopenic purpura (ITP) occurs in 2-3% of chronic lymphocytic leukemia (CLL) patients, whereas autoimmune thrombocytopenia is very rare before the diagnosis of lymphoma. A 67-year-old patient, was admitted to our Department because of purpura on his inferior limbs. Family history revealed arterial hypertension, a previous presence of hepatitis C virus (HCV) antibodies, with no sign of liver damage. Physical examination showed purpura of inferior limbs. Laboratory analysis revealed: marked thrombocytopenia (platelet count 5000/microL); hypogammaglobulinemia (9%, immunoglobulin-IgG 634 mg/dL); presence of HCV antibody (negative HCV-RNA); low-titer anti-nuclear antibody and anti-smooth muscle antibody (1:80); positive cryoglobulin (polycolonal, IgG-IgM, cryocrit 0.5%). Abdomen ultrasound revealed a mild liver steatosis and bone marrow aspirate megakaryocytic hyperplasia. Platelet kinetics study showed a markedly reduced platelet half-life (<1 day) with evident splenic uptake. The patient was treated with steroids, intravenous Ig and immunosuppressive agent (cyclophosphamide) with only temporary effect; a splenectomy was therefore performed with a subsequent durable increase in the platelet count. Two years later, the patient underwent a prostatectomy for prostate cancer and within the pelvic nodal screening the histological examination unexpectedly revealed features of B-cell non-Hodgkin's lymphoma, type CCL/small lymphocytic lymphoma; a bone marrow aspirate showed a monotypic CD5+, CD19+, CD23+ B-cell proliferation confirming the diagnosis of CLL. Six months later, a computed tomography scan revealed multiple pathological node enlargements (1.5-3 cm), compatible with a malignant lymphoma. The marked thrombocytopenia may have been an early expression of the lymphoproliferative disease. Otherwise, the association between CLL and ITP might reflect the underlying role of HCV infection causing an immune dysregulation responsible for both pathologies.

Aged↗