An automated image analysis methodology for classifying megakaryocytes in chronic myeloproliferative disorders

This work describes an automatic method for discrimination in microphotographs between normal and pathological human megakaryocytes and between two kinds of disorders of these cells. A segmentation procedure has been developed, mainly based on mathematical morphology and wavelet transform, to isolate the cells. The features of each megakaryocyte (e.g. area, perimeter and tortuosity of the cell and its nucleus, and shape complexity via elliptic Fourier transform) are used by a regression tree procedure applied twice: the first time to find the set of normal megakaryocytes and the second to distinguish between the pathologies. The output of our classifier has been compared to the interpretation provided by the pathologists and the results show that 98.4% and 97.1% of normal and pathological cells, respectively, have testified an excellent classification. This study proposes a useful aid in supporting the specialist in the classification of megakaryocyte disorders.     

Metabolic syndrome and target organ damage: role of blood pressure

A growing body of evidence indicates that the clustering of metabolic and hemodynamic abnormalities characterizing the metabolic syndrome is associated with a prevalence of subclinical damage in a variety of organs, such as left ventricular hypertrophy, thickening or atherosclerotic plaques of carotid arteries, microalbuminuria and deranged renal function. This is clinically relevant since these markers of target organ damage are associated with an increased risk of cardiovascular fatal and nonfatal events. The contribution of the metabolic syndrome to target organ damage in hypertensives is presumably responsible for a substantial increase in cardiovascular fatal and nonfatal events. Thus, target organ damage should be routinely searched for in hypertensives with metabolic syndrome in order to define initial therapeutic strategies and to monitor treatment-induced protection.     

Management of hypertension in patients with left ventricular hypertrophy

Left ventricular hypertrophy (LVH) is a cardinal manifestation of organ damage in patients with arterial hypertension. Identifying LVH is a fundamental step in evaluating hypertensive patients, because clinical and epidemiologic studies have shown this condition has a strong independent adverse prognostic significance. LVH is an integrated marker of cardiovascular risk, reflecting hypertension’s hemodynamic and nonhemodynamic effects on the heart. Reversing LVH is an intermediate goal of antihypertensive therapy. Pharmacologic strategies to reverse LVH should be based on combining two or more drugs: a renin-angiotensin system blocker (ie, angiotensin-converting enzyme inhibitor or angiotensin receptor antagonist), and a calcium antagonist or low-dose diuretic. Successful therapeutic plans should also include nonpharmacologic interventions to promote LVH regression.     

Detection of aromatase and estrogen receptors (ERalpha, ERbeta1, ERbeta2) in human Leydig cell tumor

A Leydig cell tumor is a rare neoplasm, deriving from the interstitial cells, whose pathogenesis has not been still defined. Leydig cells of normal adult testis are known as physiological targets for estrogens. However, some studies on transgenic rodents suggest a role of estrogens in the development of Leydig cell hyperplasia and Leydig cell tumor. Therefore, with the aim to evaluate a possible link between estrogens and testicular tumorigenesis, this study investigated the expression of aromatase and estrogen receptors (ERalpha, ERbeta(1), ERbeta(2)) in testes from two patients with Leydig cell tumor. A strong immunoreactivity for aromatase, ERbeta(1), and ERbeta(2), together with a detectable ERalpha immunostaining, was revealed in tumoral tissues. These findings were confirmed by western blot analysis of tumor extracts detecting a 55 kDa P450arom, a 67 kDa ERalpha band, a 59 kDa ERbeta(1) band, and a 53 kDa ERbeta(2) band. The pattern of ER expression in neoplastic cells appears different from that of control Leydig cells exhibiting only ERbeta(1) and ERbeta(2) isoforms. The authors hypothesize how the high estrogen production could play a role in the neoplastic transformation of Leydig cells, while the exclusive presence of ERalpha in tumoral cells could amplify estradiol-17beta signaling contributing to the tumor cell growth and progression.     

Neurogenic abnormalities in masked hypertension

Patients with hypertension exhibit an increased sympathetic activity. No information exists as to whether this is the case in normotensive individuals in whom there is an increased ambulatory blood pressure, a condition termed "masked" hypertension. We studied 18 middle-aged subjects with masked hypertension in whom we measured muscle sympathetic nerve traffic (peroneal nerve and microneurography) and beat-to-beat arterial blood pressure at rest and during baroreceptor deactivation and activation. Measurements also included anthropometric values and insulin sensitivity (homeostasis model assessment index). Data were compared with those of 20 normotensive subjects, 18 subjects with white-coat hypertension, and 20 patients with "in-office" and "out-of-office" hypertension. All of the individuals were pharmacologically untreated and age-matched with subjects with masked hypertension. Patients with in- and out-of-office and white-coat hypertension displayed resting sympathetic nerve activity values significantly greater than normotensive subjects (75.8+/-2.5 and 70.8+/-2.2 versus 45.5+/-2.0 bursts per 100 heartbeats respectively; P<0.01). This was the case also for masked hypertension (73.5+/-2.4 bursts per 100 heartbeats; P<0.01), the degree of the sympathetic activation being similar for magnitude to that seen in the other 2 hypertensive conditions. Compared with normotensive subjects, baroreflex-heart rate control was significantly attenuated in all of the hypertensive states, whereas baroreflex-sympathetic control was unaffected. Homeostasis model assessment index was increased in patients with in- and out-of-office and white-coat hypertension, with a further increase in masked hypertension and a direct relation with resting sympathetic nerve traffic (r=0.46; P<0.01). These data provide the first evidence that masked hypertension is characterized by a marked sympathetic overdrive. They further show that the neurogenic alterations are coupled with metabolic and baroreflex abnormalities.     

The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes

OBJECTIVE: A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. DESIGN AND METHODS: The cardiovascular cohort of the Malm? Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n=6103, DNA available on n=6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malm? Preventive Project (MPP). Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). RESULTS: Among individuals without AHT in the MDC study (n=4988) there was no difference between carriers (n=1164, 23%) and noncarriers (n=3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P = 0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the MPP and MDC studies (n=2627) there was no difference between carriers (n=607, 23%) and noncarriers (n=2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from MPP to MDC. Multivariate analysis gave no support of interaction between the CLC-Kb T481S polymorphism, gender, age or body mass index regarding their effect on BP. CONCLUSION: Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.     

How reliable is isolated clinical hypertension defined by a single 24-h ambulatory blood pressure monitoring?

BACKGROUND: Isolated clinical hypertension (ICH) is characterized by a persistently elevated clinic blood pressure in the presence of a normal day-time or 24-h ambulatory blood pressure (ABP). This definition is based on a single ABP monitoring (ABPM) and little attention has been focused on the reproducibility of this condition. OBJECTIVE: To investigate the reliability of the criteria currently recommended by major hypertension guidelines to detect ICH based on a single 24-h ABPM session. METHODS: A total of 611 never-treated grade 1 and 2 hypertensive patients (mean age 46 +/- 12 years) referred for the first time to our out-patient clinic, underwent repeated clinic blood pressure measurements, routine investigations, two 24-h periods of ABPM 1-4 weeks apart, cardiac and carotid ultrasound examinations. ABPM was always performed over a working day and the same daily activities were recommended during the two periods. ICH was diagnosed by the following criteria: (i) mean daytime values < 135/85 mmHg or (ii) mean 24-h blood pressure values < 125/80 mmHg during the first ABPM. RESULTS: The overall prevalence of ICH was 7.1% according to criterion (i) and 5.4% according to criterion (ii). Twenty (46.6%) of the 43 patients with mean daytime blood pressure values < 135/85 mmHg during the first ABPM, exceeded this cut-off value during the second ABPM period. Twenty-two (66.6%) of the 33 patients with mean 24-h blood pressure values < 120/80 mmHg during the first ABPM did not confirm a normal blood pressure profile during the second ABPM recording. Cardiovascular involvement was significantly lower in subjects with persistent normal ABP compared to those with non-reproducible ICH pattern or sustained hypertensives. CONCLUSIONS: These findings clearly indicate that: (i) the classification of ICH on the basis of a single ABPM, using the cut-offs suggested by major hypertension guidelines, has a limited short-term reproducibility and (ii) repeated ABPM recordings should be recommended to correctly diagnose patients with ICH and improve cardiovascular risk stratification.