Synthesis and biological assessment of 3,7-dihydroxytropolones.

3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development.

Cost-benefit evaluation of a preventive intervention on the biological risk in health: the accidental puncture during the administration of insulin in the University Hospital "Federico II" of Naples.

BACKGROUND: The occupational exposure to biological risk is a frequent event that affects millions of workers in the health sector. Operators are exposed to accidental contact with blood and other potentially infectious biological materials with a frequency higher than that observed in the population (occupational exposure). The pathogens most frequently implicated are the human immunodeficiency virus (HIV), hepatitis C (HCV) and hepatitis B (HBV) viruses. The World Health Organization estimates that each year more than 3 million health workers hurt themselves with an object/edge definitely contaminated with at least one HIV (about 170,000 exposures), hepatitis B (approximately 2,000,000 exposures) and hepatitis C (approximately 900,000 exposures). In Italy approximately 100,000 percutaneous exposures/year are estimated to take place. The needlestick injuries in health care workers are, in large part, preventable by adopting measures such as the use of instrumental needlesticks Prevention Devices - NPDs. The adoption of the NPDs is extremely effective in reducing occupational exposure to biological risk (from 63 % to 100 % reduction). METHODS: The aim of this study was to evaluate whether the adoption of NPDs for insulin therapy is costeffective in terms of prevention of accidents by Biohazard, compared to administration of insulin with traditional methods (syringe + vial). The estimation is carried out both in the light of current legislation (European Directive 2010/32 and 81/08 Italian Law) and epidemiological data and cost of accidents (according to frequency) and alternative interventions. RESULTS: The evaluation of cost-effectiveness included the construction of an economic model that would allow the weighting of the costs of accidents that can occur following the administration of insulin therapy with traditional methods. The economic model was developed taking into account the international literature on the phenomenon of "accidental puncture" and allowed the financial quantification of the event. Then we calculated the cost of insulin therapy using the traditional methodology and the cost has been converted to the cost of insulin therapy when administered by NPDs. The period of the study was the year 2010. CONCLUSIONS: The data thus obtained were used to evaluate the benefits of implementing NPDs for insulin therapy, in terms not only of economic advantage but also of preventive efficacy and on the cost of the accident.

[Surgical site infections in Italy]. / Le infezioni del sito chirurgico in Italia.

Surgical site infections (SSIs) are recognized as a common surgical complication, occurring in about 2-5% of all surgical procedures. SSIs represent the third most frequent nosocomial infection, accounting for 14.6% of all infections observed in hospitalised patients and 38% of those observed among surgical patients. Strategies for the prevention of SSIs also include surveillance which has proved very effective. The most recent surveillance study carried out at a national level in Italy is Kir-Nos, a multicentric study sponsored by GlaxoSmithKline and performed between April and June 2002 in 32 different General Surgery Units for a total of 2972 surgical patients enrolled. Results emerging from the study clearly indicate that many patients receive inappropriate antimicrobial prophylaxis, especially in terms of drug choice, route and timing of administration. Given the high economic burden that infections provoke, beyond the increased morbidity and mortality, it appears mandatory to improve our tools in order to reduce their incidence, as a reduction of only 0.1% can result in a considerable saving of economic resources to be allocated to other activities, such as screening and prevention programs.

Adrenal endothelin-1 levels are not associated with aldosterone secretion in primary aldosteronism.

BACKGROUND: Endothelin-1 (ET-1) may function as an aldosterone secretagogue and, in turn, aldosterone can upregulate ET-1 expression. Hence, the existence of a feedforward loop involving ETs and aldosterone has been speculated in primary aldosteronism (PA). In the present study, we sought to examine ET-1 secretion from the adrenal glands in patients with PA. DESIGN: We determined ET-1 levels in blood samples obtained during adrenal venous sampling of patients affected by PA (n=17). Furthermore, we examined the mRNA expression of the ET system in tissue samples from aldosterone-producing adenomas (APAs, n=9) and control normal adrenals (n=3). METHODS: Blood ET-1 levels were determined by RIA. Tissue mRNA expression of the ET system was assayed with Affymetrix microarrays. RESULTS: ET-1 levels did not differ between inferior vena cava and adrenal vein blood in both bilateral adrenal hyperplasia and APA patients. Moreover, cortisol-normalized ET-1 levels did not show lateralized adrenal ET-1 secretion in APAs. Through gene expression profiling with microarray performed in a distinct set of APA individuals (n=9), we confirmed the adrenal expression of a complete ET system, but we did not detect a significant upregulation of ET components within the APA tissue compared with normal adrenals. CONCLUSIONS: The present data argue against the hypothesis of increased ET-1 secretion from APAs and do not support a general role for adrenal ET-1 in the vascular pathophysiology of PA.

A nosocomial outbreak of Serratia marcescens producing inducible Amp C-type beta-lactamase enzyme and carrying antimicrobial resistance genes within a class 1 integron.

We investigated an outbreak of Serratia marcescens in the adult intensive care unit of the University Hospital of Napoli. The outbreak involved 13 cases of infection by S. marcescens over a nine-month period and was caused by a single pulsed-field gel electrophoresis clone. The epidemic strain was multiply antibiotic resistant, producing an inducible Amp C-type beta-lactamase enzyme and carrying the trimethoprim-resistance gene and the adenyltransferase gene, which confers resistance to streptomycin and spectinomycin, within a class 1 integron. Antimicrobial therapy with beta-lactams was associated with S. marcescens acquisition in the intensive care unit.

Alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes of essential hypertensives.

OBJECTIVE: The expression of alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes was investigated in 28 essential hypertensive patients as well as in the peripheral blood lymphocytes and aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. METHODS: Alpha1-adrenergic receptors were quantified by radioligand binding assays, employing [3H]-prazosin as the radioligand in association with compounds displaying different degrees of selectivity for alpha1A-, alpha1B- and alpha1D-adrenergic receptor subtypes. RESULTS: The affinity of [3H]-prazosin binding was similar in peripheral blood lymphocytes of different stage essential hypertensive and normotensive subjects or of SHR and age-matched normotensive WKY rats as well as in the aortas of SHR and WKY rats. The radioligand binding assay revealed no change in the expression of alpha1-adrenergic receptors in peripheral blood lymphocytes of essential hypertensives compared with normotensive subjects; a moderate decrease of alpha1B-adrenergic receptors and an increase of alpha1D-adrenergic receptors. The relative densities of the alpha1-adrenergic receptor subtypes were similar in the three groups of essential hypertensives. In peripheral blood lymphocytes and in aorta of SHR, [3H]-prazosin binding was significantly reduced compared with normotensive WKY rats. The expression of alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes of SHR was similar to that found in peripheral blood lymphocytes of essential hypertensives. CONCLUSIONS: Changes of lymphocyte alpha1-adrenergic receptor subtypes in essential hypertensives are similar to those observed in lymphocytes and vascular tissues of animal models of hypertension. This suggests that assays of lymphocyte alpha1-adrenergic receptors may represent an indirect marker of their involvement in essential hypertension.

Angiotensin-converting enzyme and angiotensinogen gene polymorphisms are non-randomly distributed in oral contraceptive-induced hypertension.

OBJECTIVES AND METHODS: Oral contraceptives (OC) usage increases serum angiotensinogen levels to three to five times normal and about 5% of these women develop arterial hypertension. The genetic contribution to this susceptibility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contraceptives, for three genetic polymorphisms in genes of the renin-angiotensin system: an insertion/deletion (I/ D) in the angiotensin converting enzyme (ACE) gene, the T235M polymorphism of the angiotensinogen gene (AGT) and a point mutation in its promoter. RESULTS: After cessation of oral contraception the mean arterial pressures of the hypertensive women were separable into two non-overlapping groups; 88 of the women remained hypertensive and 61 returned to normal blood pressure. Both groups of hypertensive women had a similarly higher frequency of hypertensive relatives than the normotensive women, but were otherwise similar. The 235T allele of AGT was significantly increased in frequency in the 61 oral contraceptive-inducible hypertensive women compared with the controls and the 88 women that remained hypertensive. The ACE I/D genotypes were similarly distributed within the three groups of women, but were distinctly non-random in the oral contraceptive-induced hypertensive women when they were also classified by AGT genotype. CONCLUSION: This statistical interaction of genotype frequencies suggests that the genetic basis of susceptibility to OC-induced hypertension is complex.

Peripheral adrenergic system and hypertension.

Hypertension is a condition where adrenergic responsiveness, sympathetic activity and adrenoceptors are somewhat altered. Many techniques are available to assess human sympathetic nervous system activity. They each present limitations and disadvantages. Characterization and subdivision of the alpha and beta-adrenoceptors, according to their localization and answer to different agonists, was facilitated in recent years by the extensive use of pharmacological and molecular biology techniques. Some adrenoceptor studies were conducted on animal models, human tissues and peripheral blood cells to assess their changes in various forms and stages of hypertension. Our group has pointed out that alpha1-adrenergic receptors expressed by human peripheral blood lymphocytes underwent changes of density in essential hypertensives, compared to normotensive control subjects. The importance of these findings could provide an assessment of alpha1-peripheral receptors with possible future clinical implications in the pathophysiology and treatment of hypertension.

[Histopathologic risk factors in patients with non-seminomatous germ tumors of the testis in clinical stage 1. Retrospective study of 75 patients]. / Fattori istopatologici di rischio in pazienti con tumore germinale non seminomatoso del testicolo in stadio clinico 1. Uno studio retrospettivo su 75 pazienti.

OBJECTIVES: This retrospective study was performed to evaluate histopathologic prognostic risk factors in 75 patients on clinical stage 1 nonseminomatous germ cell cancer of the testis (NSGCTT). METHODS: From September 1976 to February 2000 we operated on 75 patients for NSGCTT on clinical stage 1 disease. Average age was 29.5 years (range 16-71). After orchiectomy, therapeutic options included retroperitoneal lymph node dissection (RLND) for 44 patients (58.6%), surveillance for 26 (34.6%) and neoadjuvant chemotherapy for 5 (6.6%). Testis primary tumor samples were assessed for studying prognostic risk factors that included vascular and/or lymphatic invasion (IV/IL+), percentage of embryonal carcinoma (%EC) and absence of yolk sac tumor (YS-). RESULTS: All patients were alive and disease-free. The average age follow-up was 84.5 months (range 1-254). Relapses occurred in 11 (14.6%) patients after an average follow-up of 9.09 months (range 3-24). Prognostic risk factors were detected as follows: IV/IL+ in 17 cases (22.7%), (50-80%) EC in 23 (30.6%), CE% > 80 in 23 (30.6%), YS- in 55 (72%). In 8 (10.6%) patients there was not any prognostic risk factor. Disease relapse related to prognostic risk factors was detected as follows: 18.1% for VI/LI, 90.9% for EC% > 50 (27.2% for 50-80% EC and 63.6% for CE% > 80) and 90.9% for YS-. Relapsing rates between patients with EC% > 80 and 50-80% EC resulted statistically significant (p = 0.02, odds ratio = 12.25). Relapsing rates between patients on surveillance and those who underwent RLND was next to be significant (p = 0.05, odds ratio 3.68). CONCLUSIONS: EC% > 80 is a prognostic risk factor for disease relapse in patients with clinical stage 1 NSGCT who are selected in a high risk group requiring RPLND or neoadjuvant chemotherapy as therapeutical option.

General state of health and psychological well-being in patients after surgery for urological malignant neoplasms.

OBJECTIVE: To evaluate the general state of health and the psychological well-being in a group of 155 patients after surgery for urological malignant neoplasms. MATERIALS AND METHODS: Surgery was performed in 55 patients for renal cell carcinoma, in 54 for invasive bladder carcinoma, in 30 for adenocarcinoma of the prostate, and in 16 for squamous penile carcinoma. All patients were invited to self-compile the General Health Questionnaire (GHQ) - 12 items according to Goldberg and the Hospital Anxiety and Depression Scale. Results were compared with those in a group of patients who underwent retropubic prostatectomy for benign prostatic hyperplasia. RESULTS AND CONCLUSION: The general state of health was significantly more impaired in neoplastic patients than in the control group. Levels of anxiety were significantly higher but depression levels were similar in both groups. As far as the type of tumor is concerned, patients who underwent radical cystectomy for bladder carcinoma and those treated with partial penectomy for squamous penile carcinoma showed a significant impairment of the general state of health compared with controls. Higher levels of anxiety were observed in patients who underwent ileal conduit after radical cystectomy, in those treated with radical prostatectomy for prostate cancer and in those who underwent partial penectomy. Significantly higher levels of depression than in the control group were observed only in patients with ileal conduit.

Detection of bladder cancer by semi-automated microsatellite analysis of urine sediment.

Patients with transitional-cell carcinoma (TCC) require careful follow-up due to the high risk of recurrence. Cystoscopy and biopsy are reliable but invasive, while urine cytology is plagued by low sensitivity. It has recently been shown that allelic abnormalities detected by microsatellite analysis of DNA extracted from urine can be used to diagnose TCC with high reliability. As this analysis by classic techniques is unfeasible in a clinical setting, we performed a pilot study to determine the possibility of applying quick DNA extraction methods with laser detection and computer-based analysis of 15 fluorescently labeled PCR amplified microsatellites to detect molecular anomalies in urine sediment in 25 TCC follow-up patients. Of the eighteen cases with recurrent TCC, 14 (78%) were positive by the molecular test whereas only eight (44%) were detected by cytology. Of the seven patients with negative cystoscopy, one resulted positive by the molecular test and had recurrent TCC six-months later. Thus, this microsatellite analysis correctly predicted the clinical diagnosis in 84% (21/25) of cases, compared to 60% by cytology. The application of these semi-automated procedures allows the analysis of 18 samples with 15 markers in one day, encouraging a more expedient introduction into routine clinical use.

CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism.

Primary aldosteronism is characterized by autonomous production of aldosterone and arterial hypertension, and it occurs in 2 principal forms: aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). APA can be cured through removal of the adenoma, whereas IHA leads to hypertension that must be treated with medication. The origin of the autonomous aldosterone production in IHA is poorly understood, but genetic factors may contribute to its cause. To test the hypothesis that variants of the aldosterone synthase gene may contribute to susceptibility to IHA, we compared genotypes at 3 polymorphic sites in the CYP11B2 gene in patients with IHA (n=90) with those found in patients with APA (n=38), in patients with essential hypertension (n=72), and in normotensive individuals (n=102). We observed significant linkage disequilibrium among the 3 polymorphisms with 2 frequent haplotypes in all groups studied. One haplotype (C2R) was found to be increased in frequency in the IHA group (47%) compared with the other groups, which had a similar haplotype frequency (36%). The 3 polymorphisms studied have been implicated in either essential hypertension or excess aldosterone production in previous studies. Because of the strong linkage disequilibrium, the observed results could be due to the action of any 1 of the 3 alleles or to another allele in linkage disequilibrium with them. Our results suggest that variations in the CYP11B2 gene may contribute to dysregulation of aldosterone synthesis and lead to susceptibility to IHA.

In situ hybridization and immunocytochemistry of alpha1-adrenoceptors in human peripheral blood lymphocytes.

1 alpha1-Adrenoceptor subtypes were investigated in cytospin centrifuged preparations of human peripheral blood lymphocytes by in situ hybridization and immunocytochemistry. 2 In situ hybridization cytochemistry revealed alpha1A-, alpha1B-, and alpha1D-receptor mRNA in human peripheral blood lymphocytes. Lymphocytes hybridized for alpha1A receptor subtype represented approximately 30% of total lymphocytes, those hybridized for alpha1Beta- and alpha1D-receptor subtypes averaged 42 and 25% of total lymphocytes, respectively. 3 Cytospin centrifuged lymphocytes exposed to anti-alpha1A-, alpha1Beta- or alpha1D-receptor protein antibodies, developed specific immunostaining. Approximately 27% of total lymphocytes were immunoreactive for alpha1A-receptor protein, 40% displayed alpha1B-receptor protein immunoreactivity and 22% alpha1D-receptor protein immunoreactivity. Analysis of percentages as well as of lymphocyte morphology of in situ hybridized and immunolabelled lymphocytes suggests the co-expression of mRNA receptor signal and protein receptor immunostaining in the same lymphocyte. 4 The demonstration of both alpha1-adrenoceptor mRNA and receptor protein subtypes suggests that alpha1-adrenoceptors may have a role in regulating lymphocyte function. 5 The possibility of demonstrating receptor protein immunoreactivity in a small amount of blood, such as that required for preparing cytospin-centrifuged lymphocytes, may stimulate research to evaluate the role of these receptors in lymphocytes and to establish if assessment of lymphocyte alpha1-adrenoceptors may represent a marker of their status in health and disease.

Relationship between birth weight and blood pressure in adolescence.

BACKGROUND: Several studies have found a relation ship between small size at birth and high blood pressure (HBP). However, this association has not been fully evaluated in adolescence. The aim of the present study was to evaluate the relation of birth weight (BW) to BP in adolescence, controlling for factors related to BP, to extrauterine environment, and to maternal risk of fetal distress. METHODS: In 1310 adolescents (ages 12-14 years), randomly selected from Turin school children, we evaluated BP, heart rate (HR), weight, height, familial risk of hypertension, parental cultural level, BW, and maternal history of diseases during pregnancy. The BW-BP association was tested by using multiple regression analysis and adjusting for the other variables mentioned above. The same analysis was done for the subgroup at high risk of fetal distress. RESULTS: The association between BW and BP was negative but weak when we adjusted for all confounders (= -0.07 in males; = -0.27 in females). The association was negative and became stronger after the inclusion of all confounders, particularly HR (= -3.92), in the group of children at high risk of fetal distress. CONCLUSIONS: Intrauterine environment, as reflected by BW, has little effect on BP in early adolescence without concomitant maternal diseases or environmental conditions leading to severe placental hypoperfusion.

[Comparison of the quality of life of patients treated by surgery or radiotherapy in epidermoid cancer of the penis]. / Comparaison de la qualité de vie des patients traités pour cancer épidermoïde de la verge par chirurgie ou radiothérapie.

OBJECTIVE: The purpose of our work is to examine how partially or totally radical surgery and radiotherapy can weigh on quality of life in patients with squamous carcinoma of the penis, considering whether quality of life can be a good criterion in treatment options. MATERIAL AND METHODS: We have interviewed 17 patients alive and disease-free (average follow-up 69.43 months) after surgical treatment or radiotherapy for cancer of the penis (emasculation, 2; total amputation of the penis, 2; partial penectomy, 11; radiotherapy, 2). Tests used: General Health Questionnaire (G.H.Q.-12 by D. Goldberg); Hospital Anxiety and Depression Scale (H.A.D.S.); Social Problem Questionnaire (S.P.Q.); Overall Sexual Functioning Questionnaire (O.S.F.Q); Family APGAR Questionnaire (F.A.Q.); Performance Status ECOG. RESULTS: Thirty-five per cent of the patients presented limitations in their state of health and social problems. Anxiety was evident in 29.5% of the patients and depression in 6%. The global sexual function was compromised in 76.5%. CONCLUSION: The profile of quality of life resulted compromised in the patients who had undergone radical surgical treatment. The sexual function was the most altered component. The impact of the pathology and its treatment on the other domains of quality of life proved less significant.

Surgical treatment of penile carcinoma: our experience from 1976 to 1997.

OBJECTIVE: The purpose of this work is to evaluate our experience with the surgical treatment of penile squamous carcinoma, analyzing the therapeutic results in terms of local recurrence rates, survival and mortality rates. MATERIAL AND METHODS: From 1976 to 1997, 47 patients were treated at our institution for carcinoma of penis. Treatment of primary tumor was conservative in 8 patients (17%). Partial penectomy was performed in 30 patients (63.8%); total penectomy in 5 (10.7%) and emasculation in 4 (8.5%). Pathological stage was pTis in 2 cases (4.2%), pT1 in 20 (42.6%), pT2 in 21 (44. 7%) and pT3 in 4 (8.5%). The tumor was clinically overstaged in 13 patients (27.7%) and understaged in 4 (8.5%). Bilateral inguinal lymphadenectomy was performed only in 4 patients clinically N+ (pN2) and in 3 clinically N0 (pN0). RESULTS: Local recurrence rate was 43% in the patients with pT1 stage tumor treated conservatively. No local recurrence was observed after penectomy. 19 patients (40.4%) are alive and disease-free; 17 patients (36.2%) died of the tumor and 11 patients (23.4%) died of other causes but disease-free. Mean follow-up is 69.43 months. The overall 5-year survival rate was 34%. CONCLUSION: Partial penectomy gives better results than conservative treatment in the local management of the T1 stage tumor. Survival and mortality rates are related to both pathological and histological stages. The high mortality rate observed in the pT2 stage tumors in our experience might be related to the fact that in this stage an inguinal lymphadenectomy was not performed as a rule.

Vasoactive hormones induce nitric oxide synthase mRNA expression and nitric oxide production in human endothelial cells and monocytes.

Isoform-2 nitric oxide synthase (NOS-2) mRNA expression and nitric oxide (NO) production are induced in endothelial cells and monocytes by cytokines such as gammaIFN and LPS. We evaluated NOS-2 and isoform-3 NOS (NOS-3) mRNA expression and NO production in human monocytes and human umbilical vein endothelial cells (HUVEC), under basal conditions and after incubation with physiologic concentrations of vasoactive hormones. NOS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and NO production by electronic paramagnetic resonance spectroscopy (EPR). We showed that NOS-2 mRNA expression and NO production were induced by stimulation with epinephrine, dopamine, endothelin-1, and angiotensin II, both in monocytes and HUVEC. NOS-3 mRNA expression and NO production were detected under basal conditions in monocytes and HUVEC and were not modified by the presence of vasoactive hormones. Human endothelial cells and monocytes express the NOS-2 and NOS-3 mRNA and the inducible NOS-2 mRNA expression increases after vasoactive hormone stimulation.

alpha1-adrenergic receptor subtypes in human peripheral blood lymphocytes.

We investigated the expression of alpha1-adrenergic receptor subtypes in intact human peripheral blood lymphocytes using reverse transcription-polymerase chain reaction (RT-PCR) and radioligand binding assay techniques combined with antibodies against the three subtypes of alpha1-adrenergic receptors (alpha1A, alpha1B, and alpha1D). RT-PCR amplified in peripheral blood lymphocytes a 348-bp alpha1A-adrenergic receptor fragment, a 689-bp alpha1B-adrenergic receptor fragment, and a 540-bp alpha1D-adrenergic receptor fragment. Radioligand binding assay with [3H]prazosin as radioligand revealed a high-affinity binding with a dissociation constant value of 0. 65+/-0.05 nmol/L and a maximum density of binding sites of 175. 3+/-20.5 fmol/10(6) cells. The pharmacological profile of [3H]prazosin binding to human peripheral blood lymphocytes was consistent with the labeling of alpha1-adrenergic receptors. Antibodies against alpha1A-, alpha1B-, and alpha1D-receptor subtypes decreased [3H]prazosin binding to a different extent. This indicates that human peripheral blood lymphocytes express the three alpha1-adrenergic receptor subtypes. Of the three different alpha1-adrenergic receptor subtypes, the alpha1B is the most represented and the alpha1D, the least. Future studies should clarify the functional relevance of alpha1-adrenergic receptors expressed by peripheral blood lymphocytes. The identification of these sites may represent a step for evaluating whether they represent a marker of alpha1-adrenergic receptors in cardiovascular disorders or for assessing responses to drug treatment on these receptors.

Blood pressure and heart rate in young thalassemia major patients.

The analysis of blood pressure (BP) and heart rate (HR) variability is currently used to investigate the mechanisms responsible for cardiovascular control; therefore, we assessed whether an impairment of 24-h BP and HR profiles and sympathovagal interaction modulating cardiovascular function was present in patients with thalassemia major (TM) in preclinical phase of heart disease. Nine beta-thalassemic patients 18 years old without clinical signs of cardiac failure and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series with four harmonics was used to describe the diurnal blood pressure profile. Mean 24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were significantly lower in TM patients than in normal subjects (P < .05). A significantly higher nighttime HR value was found in TM patients (P < .05). More than 40% of the TM patients did not show a significant diurnal BP and HR rhythm. In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was significantly lower than in controls (P < .01). The night/day differences of systolic BP, diastolic BP, and HR were significantly lower in TM patients than in normals (P < .01). Furthermore, we performed power spectral analysis on short-term continuous finger BP and HR data in supine position and during passive head-up tilt. Total spectral power of systolic BP was significantly lower in patients than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM patients compared to controls (P < .05). High-frequency power of HR was significantly higher in patients than controls (P < .05). The baroreflex gain assessed by alpha-index was the same in supine position but was higher in TM patients during passive tilt (P < .05). An inverse relationship between LF/HF ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma norepinephrine levels were significantly lower in thalassemics (P < .005). In young TM patients in a preclinical stage of heart disease, these findings demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term variability of BP and HR, in particular in the LF range, showing a diminished sympathetic activity.