Reversal of MYB-dependent suppression of MAFB expression overrides leukaemia phenotype in MLL-rearranged AML.

The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Clustering spatio-temporal series of confirmed COVID-19 deaths in Europe.

The impact of the COVID-19 pandemic varied significantly across different countries, with important consequences in the definition of control and response strategies. In this work, to investigate the heterogeneity of this crisis, we analyse the spatial patterns of deaths attributed to COVID-19 in several European countries. To this end, we propose a Bayesian nonparametric approach, based on mixture of Gaussian processes coupled with Dirichlet process, to group the COVID-19 mortality curves. The model provides a flexible framework for the analysis of time series data, allowing the inclusion in the clustering procedure of different features of the series, such as spatial correlations, time varying parameters and measurement errors. We evaluate the proposed methodology on the death counts recorded at NUTS-2 regional level for several European countries in the period from March 2020 to February 2021.

Gender differences and multiple determinants of perceived physical and mental health in Italy.

Background: Perceived health is largely dependent on multiple socio-demographic and behavioral lifestyles and healthcare related factors. This could be accentuated when gender is taken into account. The aim of this study is to explore gender-related differences in multiple socio-demographic and behavioral lifestyles and healthcare related factors associated with individual health status and to identify those responsible for changes in perceived physical and mental health among men and women in Italy. Study design: We conducted a cross-sectional retrospective study to investigate the association between multiple socio-demographic and behavioral lifestyles and healthcare related factors and individual health status of 99,479 adults in Italy, using data and information obtained from a nationwide survey. Methods: To identify the factors that correlate with the perceived physical and mental health status between males and females, we employed a censored regression analysis, a Tobit model, stratifying the analysis by gender. Results: Socio-demographic and behavioral lifestyles factors differently impact on males and females and this impact is stronger on perceived physical than mental health. The perceived physical and mental health status resulted better for men than for women. The integrated analysis of gender differences in socio-demographic and behavioral lifestyles and determinants of health revealed important inequalities, mainly related to citizenship and educational level, among the socio-demographic factors, and smoking habit and obesity, among the behavioral lifestyle factors. Conclusions: Gender imbalances mainly fall into inequality in social inclusion, educational level, and healthy lifestyle. This demonstrates how gender differences are still abundantly present in the modern Italian society. Such information should be taken into consideration by policy makers when interventions to improve the health and quality of life of the population are planned or evaluated.

Axial and rotational alignment of lower limb in a Caucasian aged non-arthritic cohort.

BACKGROUND: The alignment of human lower limb has been an area of ongoing study for decades. The purpose of this study was to analyze the axial and rotational alignment from hip to ankle in a Caucasian aged non-arthritic cohort. METHODS: A non-arthritic cohort of aged patients was retrospectively analyzed by computer tomography. Anatomical-mechanical angle of femur (AMA), femur inclination (FI), femoral anteversion (FA), posterior condylar angle (PCA), proximal tibial torsion (TEAs-PTC and TEAs-PTT) and tibial fibular torsion (PTC-TFA) were measured. RESULTS: The median age of the patients was 76 years (range 67 to 91 years). Regarding axial alignment, the AMA was 5 (2.94; 6.80). No significance differences were reported by side and age. AMA was significantly lower in men. The FI was 125.3 (120.0; 134.8) with no differences in terms of side, age or gender. Regarding torsion alignment, the median values of FA, PTC-TFA and TEAs-PTT were, respectively, 16.8, 28.5 and - 1.4. No differences were reported by age. Right tibia was externally rotated by 1.5 degrees as compared to the left side (P 0.035). CONCLUSION: The broad variability of the parameters analyzed highlights the necessity for a more anatomical and individualized approach during surgery of lower limb. The present study offers the fundament to understand and treat lower limb deformities. Hence, these data can constitute the normal reference values useful to investigate lower limb malalignment. Moreover, it helps to assess the possible changes of axial and rotational alignment in idiopathic OA of lower limb. LEVEL OF EVIDENCE III: Retrospective cohort study.

Characterization of the physical, microbiological, and chemical properties of sonicated raw bovine milk.

Innovative processing technologies, such as ultrasonication, can change the properties of milk, allowing for the improvement or development of dairy foods. Yet taking bench-scale equipment to pilot plant scale has been challenging. Raw milk, standardized to 3% fat and warmed to inlet temperatures of 42 or 54°C, was exposed to continuous, high-intensity, low-frequency ultrasonication (16/20 kHz, 1.36 kW/pass) at flow rates of 0.15, 0.30, and 0.45 L/min that resulted in resident times within the reaction cell of 6, 3, and 2 min per pass, respectively. Multiple passes (3, 5, and 7, respectively) were required to obtain a total exposure time of 14 to 18 min. Evaluation of fat droplet sizes, enzyme coagulation properties, and microstructure of milk and milk gels, as well as determining compositional and lipid properties, were conducted to determine the potential of the ultrasound system to effectively modify milk. Laser scanning particle sizing and confocal microscopy showed that the largest droplets (2.26 ± 0.13 µm) found in raw milk were selectively reduced in size with a concomitant increase in the number of submicron droplets (0.37 ± 0.06 µm), which occurred sooner when exposed to shorter bursts of ultrasonication (0.45 L/min flow rates) and at an inlet temperature of 54°C. Ultrasound processing with milk entering at 42°C resulted in faster gelling times and firmer curds at 30 min; however, extended processing at inlet temperature of 54°C reduced curd firmness and lengthened coagulation time. This showed that ultrasonication altered protein-protein and protein-lipid interactions, thus the strength of the enzyme-set curds. Scanning electron microscopy revealed a denser curd matrix with less continuous and more irregular shaped and clustered strands, whereas transmission electron microscopy showed submicron lipid droplets embedded within the protein strands of the curd matrix. Processing at inlet temperature of 54°C with flow rates of 0.30 and 0.45 L/min also reduced the total aerobic bacterial count by more than 1 log cfu/mL, and the number of psychrophiles below the limit of detection (10 cfu/mL) for this study. Ultrasonication exposures of 14 to 18 min had minimal effect on the milk composition, fatty acid profiles, and lipid heat capacity and enthalpy. The findings show that this continuous ultrasound system, which is conducive to commercial scale-up, modifies the physical and functional properties of milk under the parameters used in this study and has potential use in dairy processing.

The effects of microfluidization on the physical, microbial, chemical, and coagulation properties of milk.

This work examines the use of mild heat treatments in conjunction with 2-pass microfluidization to generate cheese milk for potential use in soft cheeses, such as Queso Fresco. Raw, thermized, and high temperature, short time pasteurized milk samples, standardized to the 3% (wt/wt) fat content used in cheesemaking, were processed at 4 inlet temperature and pressure conditions: 42°C/75 MPa, 42°C/125 MPa, 54°C/125 MPa, and 54°C/170 MPa. Processing-induced changes in the physical, chemical, and microbial properties resulting from the intense pressure, shear, and cavitation that milk experiences as it is microfluidized were compared with nonmicrofluidized controls. A pressure-dependent increase in exit temperature was observed for all microfluidized samples, with inactivation of alkaline phosphatase in raw and thermized samples at 125 and 170 MPa. Microfluidization of all samples under the 4 inlet temperature and processing pressure conditions resulted in a stable emulsion of fat droplets ranging from 0.390 to 0.501 µm, compared with 7.921 (control) and 4.127 (homogenized control) µm. Confocal imaging showed coalescence of scattered fat agglomerates 1 to 3 µm in size during the first 24 h. We found no changes in fat, lactose, ash content or pH, indicating the major components of milk remained unaffected by microfluidization. However, the apparent protein content was reduced from 3.1 to 2.2%, likely a result of near infrared spectroscopy improperly identifying the micellar fragments embedded into the fat droplets. Microbiology results indicated a decrease in mesophilic aerobic and psychrophilic milk microflora with increasing temperature and pressure, suggesting that microfluidization may eliminate bacteria. The viscosities of milk samples were similar but tended to be higher after treatment at 54°C and 125 or 170 MPa. These samples exhibited the longest coagulation times and the weakest gel firmness, indicating that formation of the casein matrix, a critical step in the production of cheese, was affected. Low temperature and pressure (42°C/75 MPa) exhibited similar coagulation properties to controls. The results suggest that microfluidization at lower pressures may be used to manufacture high-moisture cheese with altered texture whereas higher pressures may result in novel dairy ingredients.

Beneficial effects of carotenoid-producing cells of Bacillus indicus HU16 in a rat model of diet-induced metabolic syndrome.

A well-established rat model of diet-induced metabolic syndrome was used to evaluate the effects of the oral administration of spores or cells of HU16, a carotenoid-producing strain of Bacillus indicus. Symptoms of metabolic syndrome were induced in 90-days old, male Sprague-Dawley rats maintained for eight weeks on a high-fat diet, as previously reported. Parallel groups of animals under the same diet regimen also received a daily dose of 1×1010 cells or spores of B. indicus HU16. Cells of strain HU16 were able to reduce symptoms of metabolic syndrome, plasma markers of inflammation and oxidative markers in plasma and liver to levels similar to those observed in rats under a standard diet. HU16 cells did not affect obesity markers or the accumulation of triglycerides in the liver of treated animals. Denaturing gradient gel electrophoresis analysis showed that the oral administration of HU16 cells did not significantly affect the gut microbiota of high fat-fed rats, suggesting that the observed beneficial effects are not due to a reshaping of the gut microbiota but rather to metabolites produced by HU16 cells.

Multifocal, multicentric and contralateral breast cancers: breast MR imaging in the preoperative evaluation of patients with newly diagnosed breast cancer.

PURPOSE: This study was done to verify the usefulness of preoperative breast magnetic resonance (MR) imaging in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: A retrospective analysis of 291 patients with invasive breast cancer newly diagnosed with conventional breast imaging (mammography and ultrasound) was performed. All patients underwent MR imaging prior to surgery. The MR imaging detection rate of additional malignant cancers occult to mammography and ultrasound was calculated. Data were analysed with Fisher's exact test (p<0.05) according to the following parameters: histopathological features of the index tumour (histological type and size) and mammographic density [according to the Breast Imaging Reporting and Data System (BI-RADS) classification from 1 fatty to 4 dense). The gold standard was the histological examination on the surgical specimen. RESULTS: MR imaging identified 40 mammographically and sonographically occult malignant lesions other than the index cancer in 27/291 patients (9%). These additional cancers were located in the same quadrant as the index cancer in 13 women (4%), in a different quadrant in 12 (4%) and in the contralateral breast in the remaining two (1%). The cancer detection rate in the subgroup of index cancers with lobular histological type was 25%, significantly higher (p=0.03) than the detection rate of 11% recorded in the subgroup of ductal cancers. The cancer detection rate in the subgroup of index cancers >2 cm was 27%, significantly higher (p=0.001) than the rate of 8% found in the subgroup of index cancers <2 cm. Mammographic density was not correlated (p=0.48) with MR detection of additional cancer, with 14% of additional malignancies being detected in both dense and fatty breasts. CONCLUSIONS: In patients with newly diagnosed invasive breast cancer, preoperative MR imaging is useful for detecting additional synchronous malignancies that are not detected on conventional breast imaging. The cancer detection rate is 9%. The use of preoperative MR imaging as an adjunct to conventional breast imaging in women with an infiltrating lobular index cancer and an index cancer >2 cm is especially beneficial.

MR-guided vacuum-assisted breast biopsy in the management of incidental enhancing lesions detected by breast MR imaging.

PURPOSE: The objective of this study was to determine the clinical value and accuracy of magnetic resonance (MR)-guided vacuum-assisted breast biopsy (VAB). MATERIALS AND METHODS: We retrospectively analysed 106 incidental breast lesions detected on MR imaging in 98 patients. Patients with nonpalpable suspicious lesions that were only MR visible were referred for MR-VAB performed with a 10-gauge needle. All patients with a VAB diagnosis of infiltrating carcinoma, carcinoma in situ or atypical epithelial hyperplasia were referred for surgery. Histopathology of the surgical specimen was considered the reference standard. RESULTS: MR-guided VAB was attempted in 29/106 lesions (27%); in 2/29 patients, the procedure could not be performed owing to failure to visualise the lesion. Lesions with clearly malignant features and borderline lesions (atypical ductal hyperplasias) were identified in 12 cases (44%) and benign entities in 15 (56%). Seven of 12 (58%) malignant lesions were <10 mm. Among the 27 successful MR-VAB procedures, VAB yielded one false-negative diagnosis (4%) and underestimation (4%). MR-guided VAB sensitivity and specificity were 92% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 93%. CONCLUSIONS: The results of this study indicate that MR-guided VAB offers good accuracy in characterising nonpalpable breast lesions visible on MR imaging alone. Small lesion size (<1 cm) did not prove to be a limitation for the success of the procedure.

Allogeneic hemopoietic stem cell transplantation in solid tumors.

The existence of a graft versus tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation is well established as a critical component for the success of the procedure in several hematologic malignancies. Although it has been suggested that a GVT effect might also be generated in patients affected by refractory solid tumors, the morbidity of conventional allogeneic hematopoietic stem cell transplantation has limited its investigation in these diseases. Recently introduced allogeneic nonmyeloablative regimens have greatly decreased morbidity and mortality related to transplants which retain a powerful GVT. On this basis, it has become possible to explore the existence of alloreactivity toward solid tumors. The present article reviews the early clinical results of this novel immunotherapeutic approach for solid tumors.

Efficacy, safety and tolerability of combined low-dose simvastatin-fenofibrate treatment in primary mixed hyperlipidaemia.

OBJECTIVE: In order to assess the long-term (12 months) efficacy and safety of fenofibrate administered with simvastatin in the treatment of primary mixed hyperlipidaemia, we conducted a study that compared increasing dosages of these drugs in subgroups of men and women belonging to a clinical sample of out-patients. DESIGN: This was an open study carried out in patients with primary mixed hyperlipidaemia (lipoprotein phenotype IIb) who needed a combined therapeutic approach because of their poor response to a single-drug regimen with an HMG-CoA reductase inhibitor (simvastatin). Thus, a fibrate (fenofibrate) was added to the therapy. The study lasted 12 months. PATIENTS: Forty-five patients (mean age: 58.9 +/- 11.3 years) with primary mixed hyperlipidaemia who showed a poor response to the single-drug hypolipidaemic treatment were enrolled. Their average plasma triglyceride level was consistently above 300 mg/dL and low-density lipoprotein cholesterol (LDL-C) was over 160 mg/dL after at least 6 months of a single hypolipidaemic drug (simvastatin) regimen plus antiatherogenic dietary treatment. INTERVENTIONS: Five patients received simvastatin 10mg once daily in addition to fenofibrate 200mg; 26 patients received simvastatin 20mg once daily plus fenofibrate 200mg; 11 patients received simvastatin 20mg once daily plus fenofibrate 300mg; and three patients received simvastatin 30mg once daily plus fenofibrate 200mg. The patients were allocated to treatment groups on the basis of their relative response to the therapy. Those making up the progressively higher agent/dose groups were the individuals at higher cardiovascular risk according to the total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) values. RESULTS: The double-drug regimen given for 12 months to four different groups, according to the different combined dosages of simvastatin and fenofibrate, resulted in a reduction in total cholesterol of 18% (p

Immunoadsorption apheresis (Selesorb) in the treatment of chronic hepatitis C virus-related type 2 mixed cryoglobulinemia.

In this short-term open label clinical pilot study, conducted at one center, the immune complex dextran sulphate adsorber (Selesorb) was used to treat four female patients aged 59-69 with HCV-related cryoglobulinaemia, vasculitis and/or neuropathy. The primary trial objective was to assess the clinical efficacy of the immunoadsorber. The secondary objective of the trial was to determine the safety of the adsorber and to investigate the adsorption capacity, measured as the adsorption of cryoglobulin-related immune complexes and the resulting influence on plasma components of the immune system. The patients have been submitted to treatment with the immunoadsorber, at approximately 1-3 days intervals, completing six sessions. The follow-up was one month. In the patients treated with Selesorb, we observed a statistically significant decrease in plasma of all classes of immunoglobulins (IgA: 5-28%; IgG: 14-44%; IgM: 8-38%). In two patients with peripheral neuropathy secondary to cryoglobulinemia, the symptomatology was improved. In a third patient the neurological involvement was substantially unchanged, and the same unsuccessful outcome was observed for Sjögren syndrome is concerned. Nevertheless, the two patients with lower extremity vasculitis showed an appreciable improvement. We failed to observe significant side effects directly related to the use of this immunoadsorbent.

Circulating homocysteine levels in sustained and white coat hypertension.

Although white coat hypertension has been widely studied in the last years, its risk profile is not yet completely clear. The aim of this study was to evaluate circulating homocysteine levels, an emerging cardiovascular risk factor, in subjects with white coat and sustained hypertension. We selected 31 sustained hypertensive subjects, 31 white coat hypertensive subjects and 31 normotensive subjects matched for age, gender, body mass index and occupation. Women were also matched for menopausal status. Subjects with smoking habit, dyslipidaemia and diabetes mellitus were excluded from the study. White coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <135/85 mmHg. Blood samples were drawn after a fasting period of 12 h for routine laboratory tests and homocysteine determination. Homocysteine levels were evaluated by fluorescence polarization immunoassay. Creatinine, glucose, cholesterol and triglycerides were not different among the groups. White coat hypertensive subjects had significantly lower homocysteine levels than sustained hypertensive patients (8.2+/-2.0 vs 12.6+/-3.9 micromol/l, P=0.0003). No significant difference was observed between white coat hypertensive and normotensive subjects regarding this parameter (8.2+/-2.0 vs 7.6+/-1.9 micromol/l, P=0.9). In conclusion, our data show that middle-aged white coat hypertensive subjects without other cardiovascular risk factors have lower circulating homocysteine levels than sustained hypertensive patients suggesting that they are at lower cardiovascular risk.

An alternative inexpensive treatment for deep sternal wound infections after sternotomy.

We present three cases of deep sternal wound infections after sternotomy, with partial dehiscence and instability of sternum, successfully treated with combined therapy based on hyperbaric oxygen (HBO), parenteral and intranasal antibiotics, daily debridements and medications. After a short hospitalization (10 days) to detect involved bacteria, depth of the wounds and choice of right antibiotic therapy, all patients continued the treatment as outpatients, undergoing daily medications and antibiotic therapy before every HBO session. After 3 months the sternal wounds were completely epithelialized. This conservative therapy for deep sternal wound infections can be an alternative and inexpensive approach to surgical treatment. The aggressive surgical approach could be limited for those deep sternal wounds associated with broad dehiscence and instability of sternum, complicated by paradoxical breathing and/or mediastinitis and alteration of respiratory system mechanics.

Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia.

The objective of the present study was to assess the effect of consumption of a yoghurt-based drink enriched with 1-2 g plant sterols/d on serum lipids, transaminases, vitamins and hormone status in patients with primary moderate hypercholesterolaemia. Thirty patients were randomly assigned to one of two treatment groups: a low-fat low-lactose yoghurt-based drink enriched with 1 g plant sterol extracted from soyabean/d v. a low-fat low-lactose yoghurt, for a period of 4 weeks. After a 2-week wash-out period, patients were crossed over for an additional 4-week period. Second, after a 4-week wash-out period, eleven patients were treated with 2 g plant sterols/d in a second open part of the study for a period of 8 weeks. The yoghurt enriched with plant sterols significantly reduced, in a dose-dependent manner, serum total cholesterol and LDL-cholesterol levels and LDL-cholesterol:HDL-cholesterol (P<0.001), whereas no changes were observed in HDL-cholesterol and triacylglycerol levels, either in the first or the second part of the study. There were only slight, not statistically significant, differences in serum transaminase, vitamin and hormone levels. To conclude, a low-fat yoghurt-based drink moderately enriched with plant sterols may lower total cholesterol and LDL-cholesterol effectively in patients with primary moderate hypercholesterolaemia.

Behavior of small thyroid cancers found by screening radiation-exposed individuals.

Thyroid cancers detected by screening irradiated individuals are often small and of uncertain clinical significance. We retrospectively analyzed the effect of screening in a cohort of 4296 individuals exposed to radiation as children in the 1940s and 1950s and followed by us from 1974 until the present. We compared the thyroid cancers diagnosed before 1974 (122 cases, routine care) with the cancers found in subjects screened by us after 1974 (172 cases, screened), using cancer recurrence as the end point. Screening included a thyroid scan or, more recently, thyroid ultrasound. As expected, many of the cancers found by screening were very small (52% were <10 mm), but the range of tumor sizes overlapped those found by routine care. The recurrence rate was significantly lower in the cases found by screening, but when the comparison was limited to cancers 10 mm or larger, no difference in the recurrence rates was seen. This would suggest that the lower recurrence rate observed for small thyroid cancers detected at screening was due to earlier diagnosis rather than more effective treatment. By univariate analysis, four factors were associated with an increased risk of recurrence of small (<10 mm) thyroid cancers: short latency (i.e. a shorter time interval between the radiation exposure and the first thyroid surgery), lymph node metastases present at diagnosis, multifocal cancers, and higher radiation dose. In a multivariate analysis combining the four risk factors, only short latency was significant. As thyroid cancers that escape detection by routine means should be diagnosed at screening, and both large and small thyroid cancers have the potential to recur, screening may be of value, but only if groups with a sufficiently high prevalence of thyroid cancer can be identified to offset the adverse effects of unnecessary treatment due to false positive results.

Endogenous ouabain and hemodynamic and left ventricular geometric patterns in essential hypertension.

We sought to evaluate the relationships among circulating levels of an endogenous ouabain-like factor (EO) and systemic hemodynamics and left ventricular (LV) geometry in patients with recently diagnosed essential hypertension. We selected 92 never-treated patients with essential hypertension. Blood samples were drawn for estimation of plasma EO (radioimmunoassay) and subjects underwent echocardiographic examination to evaluate LV end-systolic and end-diastolic wall thickness and internal dimensions. LV volumes, stroke volume, cardiac output, total peripheral resistance, LV mass, and relative wall thickness were calculated, and all except the last parameter were indexed by body surface area. LV mass also was indexed by height. On the basis of the values of LV mass index (body surface area or height) and relative wall thickness, subjects were divided into groups with either normal geometry, concentric remodeling, concentric hypertrophy, or eccentric nondilated hypertrophy. In the study population as a whole, circulating EO levels were significantly and directly correlated with mean blood pressure (r = 0.21, P = .048), relative wall thickness (r = 0.34, P = .001), and total peripheral resistance index (r = 0.37, P = .0003). Plasma EO also was significantly and inversely correlated with LV end-diastolic volume index (r = -0.32, P = .002), stroke index (r = -0.34, P = .0009), and cardiac index (r = -0.35, P = .0007). In multiple regression analysis, plasma EO was an independent correlate of total peripheral resistance index, cardiac index, and relative wall thickness. Regardless of the indexation method used for LV mass, plasma EO was higher in patients with concentric remodeling than in those with either normal geometry or concentric hypertrophy. Plasma EO tended to be higher (indexation by body surface area) or was significantly higher (indexation by height) in subjects with concentric remodeling than in those with eccentric nondilated hypertrophy. Patients with concentric remodeling showed the highest total peripheral resistance index and the lowest cardiac index. Our data suggest that EO plays a role in regulating systemic hemodynamics and LV geometry in patients with essential hypertension.

Effects of dietary virgin olive oil phenols on low density lipoprotein oxidation in hyperlipidemic patients.

The aim of this study was to assess the effects of the dietary intake of extra virgin olive oil on the oxidative susceptibility of low density lipoproteins (LDL) isolated from the plasma of hyperlipidemic patients. Ten patients with combined hyperlipidemia (mean plasma cholesterol 281 mg/dL, triglycerides 283 mg/dL) consumed a low-fat, low-cholesterol diet, with olive oil (20 g/d) as the only added fat, with no drug or vitamin supplementation for 6 wk. Then they were asked to replace the olive oil they usually consumed with extra virgin olive oil for 4 wk. LDL were isolated at the beginning, and after the 4 wk of dietary treatment. LDL susceptibility to CuSO4-mediated oxidation was evaluated by measuring the extent of lipid peroxidation. We also determined fatty acid composition and vitamin E in plasma and LDL and plasma phenolic content. Extra virgin olive oil intake did not affect fatty acid composition of LDL but significantly reduced the copper-induced formation of LDL hydroperoxides and lipoperoxidation end products as well as the depletion of LDL linoleic and arachidonic acid. A significant increase in the lag phase of conjugated diene formation was observed after dietary treatment. These differences are statistically correlated with the increase in plasma phenolic content observed at the end of the treatment with extra virgin olive oil; they are not correlated with LDL fatty acid composition or vitamin E content, which both remained unmodified after the added fat change. This report suggests that the daily intake of extra virgin olive oil in hyperlipidemic patients could reduce the susceptibility of LDL to oxidation, not only because of its high monounsaturated fatty acid content but probably also because of the antioxidative activity of its phenolic compounds.

Clinic and ambulatory heart rate in sustained and white-coat hypertension.

BACKGROUND: Sustained and white-coat hypertensives show hypertension in the office setting but different blood pressure values outside the clinical environment. So far, only a few incomplete data on heart rate are available inside and outside the clinical setting in these groups of patient. The aim of this study was to evaluate clinic and ambulatory heart in sustained hypertensives, white-coat hypertensives and normotensives. METHODS: We selected 236 sustained hypertensives, 236 white-coat hypertensives and 236 normotensives matched for age, gender and body mass index, and with a similar occupation. The subjects had been submitted to clinic evaluation and the non-invasive monitoring of blood pressure and heart rate. White-coat hypertension was defined as clinic hypertension and a daytime blood pressure of less than 135/85 mmHg. RESULTS: The clinic heart rate was significantly higher in sustained hypertensives and white-coat hypertensives than in normotensives (76 +/- 11 versus 75.5 +/- 10 versus 70 +/- 9 beats/min [bpm], respectively, P < 0.05). The daytime heart rate was significantly higher in sustained hypertensives than in white-coat hypertensives and normotensives (79.4 +/- 10 versus 74.6 +/- 8.5 versus 74.5 +/- 8.5 bpm, respectively, P < 0.05), as were the night-time heart rate (67 +/- 8.5 versus 63 +/- 8 versus 63 +/- 8 bpm, respectively, P < 0.05) and 24 h heart rate (76.3 +/- 9 versus 72 +/- 7.8 versus 72 +/- 8 bpm, respectively, P < 0.05). When men and women were analyzed separately, the same trend was observed. CONCLUSIONS: The clinic heart rate is similar in sustained and white-coat hypertensives, but the ambulatory heart rate is lower in white-coat hypertensives. As ambulatory heart rate is more representative of 24 h heart rate load and may be a better indicator of the detrimental effect of heart rate, our findings suggest that white-coat hypertensives are at lower cardiovascular risk than sustained hypertensives.

Twenty-four-hour autonomic nervous function in sustained and "white coat" hypertension.

BACKGROUND: It is unknown whether "white coat" hypertension, also known as isolated clinic hypertension, shares similarities in pathophysiologic background with sustained hypertension. Therefore we evaluated 24-hour autonomic nervous function in sustained and white coat hypertension. METHODS: We selected 12 patients with sustained hypertension (clinic blood pressure >/=140/90 mm Hg and daytime blood pressure >135/85 mm Hg) and 12 patients with white coat hypertension (clinic blood pressure >/=140/90 mm Hg and daytime blood pressure <135/85 mm Hg) from patients undergoing ambulatory blood pressure monitoring and 12 normotensives for study inclusion. Groups were matched for age, sex, and body mass index and had similar dietary pattern and occupational status (civil servants with sedentary jobs). Subjects underwent noninvasive 24-hour monitoring of blood pressure, R-R interval of the electrocardiogram, body position, activity rate, and ambient temperature. Power spectral analysis of R-R intervals was performed with an autoregressive model to obtain the low-frequency component, the high-frequency component, and their ratio. Subjects also collected 24-hour urine samples for examination of norepinephrine and epinephrine excretion by high-performance liquid chromatography. RESULTS: Work and sleep time, body position, ambient temperature, and activity were not different among the groups. Daytime, nighttime, and 24-hour low-frequency/high-frequency ratios were significantly higher in patients with sustained hypertension than in patients with white coat hypertension (3.4 +/- 0.45 vs 2.65 +/- 0.45, 2.35 +/- 0.60 vs 1. 82 +/- 0.45, and 3.04 +/- 0.45 vs 2.4 +/- 0.35, respectively, P <. 05). Urinary norepinephrine excretion (53 +/- 12 microg vs 29.5 +/- 6 microg; P <.05) and vanillylmandelic acid excretion (4.45 +/- 0.6 mg vs 3.1 +/- 0.55 mg; P <.05) during the 24 hours were significantly higher in patients with sustained hypertension than in those with white coat hypertension. There was no difference between those with white coat hypertension and normotensives concerning the aforementioned parameters. CONCLUSIONS: Our findings indicate whole-day sympathetic overactivity in sustained hypertension but not in white coat hypertension, suggesting that these conditions show some differences in pathophysiologic background.