Prevalence by sex of preclinical carotid atherosclerosis in newly diagnosed type 2 diabetes.

BACKGROUND AND AIMS: There is clinical trial evidence that only early, intensive risk factor control can reduce cardiovascular disease (CVD) morbidity and mortality in type 2 diabetes (T2DM). However, there is little information regarding preclinical atherosclerosis at diabetes diagnosis. We assessed carotid atherosclerosis in new-onset T2DM and control individuals without prior CVD. METHODS AND RESULTS: In a cross-sectional case-control study, we determined intima-media thickness (IMT) and plaque (IMT ≥1.5 mm) by ultrasound at all carotid sites in new-onset T2DM patients and controls. We assessed 106 T2DM patients, median age 62 years, 46% women, 19% smokers, 54% with hypertension, and 41% with dyslipidemia and 99 non-diabetic subjects matched by age, sex, and cardiovascular risk factors. Compared to controls, T2DM patients had higher common carotid artery (CCA)-IMT (median 0.725 vs. 0.801 mm, p = 0.01), bulb-IMT (0.976 vs. 1.028 mm, p = 0.12), and internal carotid artery (ICA)-IMT (0.727 vs. 0.802 mm, p = 0.04). The prevalence of total plaque (60% vs. 72%, p = 0.06), ICA plaque (20% vs. 42%, p < 0.01), and harboring ≥3 plaques (16% vs. 35% p < 0.01) was also higher in T2DM. Plaque score (sum of maximum plaque heights) was also higher (p < 0.01) in T2DM. Diabetic women showed more advanced carotid atherosclerosis than diabetic men when they were compared with their respective non-diabetic counterparts. CONCLUSIONS: There is a high prevalence of preclinical atherosclerosis (carotid plaque presence and burden) in new-onset T2DM subjects, especially in women. Early, still reversible, preclinical atherosclerosis may explain in part why early intervention is effective to prevent CVD in this patient population.

Carotid atherosclerosis and lipoprotein particle subclasses in familial hypercholesterolaemia and familial combined hyperlipidaemia.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) and familial combined hyperlipidaemia (FCH) are common atherogenic disorders with great variability in cardiovascular disease (CVD). No direct atherosclerosis burden comparisons have been performed between FH and FCH in relation to lipoprotein particle distribution. METHODS AND RESULTS: Risk factors and three measures of carotid intima-media thickness (IMT) in both sides were determined in 572 FH, 250 FCH and 200 controls. Lipoproteins were assessed by nuclear magnetic resonance (NMR) spectroscopy. Compared with controls, IMT measures were increased in FH and FCH. FCH had the highest adjusted mean-maximum IMT. FH had twice low-density lipoprotein (LDL) particles than controls, but similar LDL subclass size and distribution. FCH subjects also had increased LDL particles and the highest number of small LDL (1519 ± 731 nmol l(-1) vs. 887 ± 784 nmol l(-1) in FH and 545 ± 409 nmol l(-1) in controls). Age, gender, cholesterol/high-density lipoprotein (HDL) ratio, smoking and systolic blood pressure were independently associated with IMT in FH (r(2) = 0.38). The same variables, except cholesterol/HDL ratio, were associated with IMT in FCH (r(2) = 0.40). Among NMR lipoproteins, only VLDL and chylomicrons increased IMT prediction in FCH by 0.8%. CONCLUSION: FH and FCH subjects show increased carotid atherosclerosis in relation to classical risk factors. Lipoprotein subclasses do not substantially contribute to IMT variability.

[Study of satisfaction of testicular prosthesis implantation in children]. / Estudio de satisfacción de la implantación de prótesis testiculares en niños.

UNLABELLED: Testicular absence may cause psychological trauma in children. It can be avoided by placing testicular prosthesis (TP). However there is no consensus on the optimal age of implantation. We evaluate the results of TP implantation and their complications, as well as patient and family satisfaction. MATERIAL AND METHODS: This is a retrospective study of TP implanted between 2004-2010 in our center. Variables analyzed are: age, size and side, indication, surgical technique, complications and comorbidity. Telephone survey was done by a single interviewer to 50 families. DATA COLLECTED: general family satisfaction, characteristics of the prosthesis (size, shape, location and consistency), body image and psychological situation of the child, duration of analgesia after surgery, reoperation rate, and family advice to other parents. Statistical analysis with SPSS-18.0. RESULTS: 107 prostheses were placed (4 bilateral, 64 left and 35 rights) at a mean age of 70,10 +/- 58,6 months. The most common indication was cryptorchidism (48.2%). Initial inguinal approach in 69%, and simultaneous contralateral orchidopexy in 29.9%. Only one patient refused the prostheses. In 71% the mother was interviewed. Parents consider size, shape and position appropriate in 55.6%, 66.7% and 82.22% respectively. Hard consistency of TP was considered in 82.3% of the patients. Psychological problems were absent in 86.7%. Nighty five percent would be willing to replace when it was necessary. Parents would recommend the intervention to parents in the same situation in 86.7%. CONCLUSION: Testicular prosthesis avoids psychological trauma. The lack of satisfaction regarding to the small size and hardness makes necessary to replace the TP in adulthood. An open question remains whether we should consider the placement of TP in early ages, or if we should establish some indications based on a more rational communication with the family.

Impact of carotid atherosclerosis as assessed by B-mode ultrasonography on the evolution of kidney transplantation.

UNLABELLED: Carotid arteriosclerosis is a marker of cardiovascular risk in the general population. Cardiovascular disease is highly prevalent in kidney transplant recipients. This study analyzed the impact of arteriosclerotic carotid lesions on the evolution of renal transplant recipients. METHODS: This prospective study was performed in 70 patients with renal transplantations (mean age 52 +/- 12 years; 67% men (n = 47). High-resolution B-mode ultrasonography (7.5 MHz) of both carotid arteries was performed at baseline to assess carotid caliber, mean and maximum intima-media thickness (IMT), presence of arteriosclerotic plaques (number and maximum height), and percentage stenosis. We analyzed the impact of carotid arteriosclerosis and various donor-recipient clinical covariables on long-term patient and graft survival. RESULTS: Mean follow-up was 9.7 +/- 2.5 years (2-14). Atheroma plaques were detected in 74% of patients (n = 52). The mean number of plaques was 3.96 +/- 2.88 and maximum plaque height was 2.49 +/- 0.97 mm. IMT was 0.71 +/- 0.21 mm (0.4-1.5) with 27% of patients (n = 19) having an IMT value greater than 0.8 mm. Sonographic signs of occlusion were evident in 13% (n = 9) and the mean occlusion was 33 +/- 11% (range 20%-45%). The presence of plaques was significantly associated with age (P = .002), hypertension and diabetes (P = .016), and hypercholesterolemia (P = .01). There was an association between age and arterial wall thickness (P = .042). Acute rejection was an independent risk factor for graft loss (OR 8.14, P = .003). The multivariate study identified carotid wall thickness as an independent risk factor for patient death (OR 12.7, P = .017). CONCLUSION: Carotid arteriosclerosis is highly prevalent among renal transplant recipients. Carotid lesions were an independent risk factor for long-term patient death. High-resolution ultrasound imaging of the carotid arteries was a useful, noninvasive diagnostic technique for accurate assessment of cardiovascular risk in renal transplant recipients.

Predicting the development of liver cirrhosis by simple modelling in patients with chronic hepatitis C.

BACKGROUND: Data are scarce on the natural history of chronic hepatitis C (CHC) in patients with mild hepatitis C who did not respond to anti-viral therapy. AIM: To predict the risk of progression to cirrhosis, identifying patients with the more urgent need for therapy with effective anti-virals. METHODS: A cohort of 1289 noncirrhotic CHC patients treated with interferon-based therapy between 1990 and 2004 in two referral hospitals were followed up for a median of 12 years. RESULTS: Overall, SVR was achieved in 46.6% of patients. Data from a randomly split sample (n = 832) was used to estimate a model to predict outcomes. Among nonresponders (n = 444), cirrhosis developed in 123 (28%) patients. In this group, the 3, 5 and 10-year cumulative probabilities of cirrhosis were 4%, 7% and 22%, respectively, compared to <1% in the SVR-group (P < 0.05). Baseline factors independently associated with progression to cirrhosis in nonresponders were: fibrosis ≥F2, age >40 years, AST >100 IU/L, GGT >40 IU/L. Three logistic regression models that combined these simple variables were highly accurate in predicting the individual risk of developing cirrhosis with areas under the receiving operating characteristic curves (AUC) at 5, 7 and 10 years of ~0.80. The reproducibility of the models in the validation cohort (n = 457, nonresponders = 244), was consistently high. CONCLUSIONS: Modelling based on simple laboratory and clinical data can accurately identify the individual risk of progression to cirrhosis in nonresponder patients with chronic hepatitis C, becoming a very helpful tool to prioritise the start of oral anti-viral therapy in clinical practice.

Utility of pulsed Doppler in the diagnosis and follow-up of acute vascular graft rejection treated with OKT3 monoclonal antibody or antilymphocyte serum.

Fifteen patients with severe acute vascular graft rejection (twelve of them steroid-resistant) treated with OKT3 monoclonal antibody (8) or antilymphocyte serum (7) were sequentially studied with duplex-Doppler ultrasonography (DDUS). Measurements of intrarenal resistance were obtained by means of the resistive index (RI). During rejection episodes, the intrarenal resistance was increased in all patients (RI range: 0.89-1), with absent or reversed diastolic blood flow. Normalization of diastolic blood flow was documented prior to the decrease of serum creatinine level in all patients who recovered from a rejection episode. We conclude that DDUS is a noninvasive technique useful in the diagnosis and monitoring of acute vascular graft rejection. Prediction of graft outcome after rejection treatment could probably be made based on DDUS findings.

Effects of time of storage, albumin, and osmolality changes on outflow facility (C) of bovine anterior segment in vitro.

PURPOSE: To analyze the influence of time of storage, the presence of albumin at physiological concentrations, and the perfusion with anisosmotic media on the aqueous humor outflow facility (C) of isolated bovine anterior segments (AS). METHODS: Anterior segments dissected from cow eyes were perfused at a constant pressure of 10 mm Hg with Dulbecco's modified Eagle's medium (DMEM; osmolality 300 mOsm/kg), with hyposmotic media (150, 210, and 270 mOsm/kg), or with hyperosmotic media (360, 420, and 480 mOsm/kg). Outflow facility was calculated every 5 seconds as the ratio between average inflow from the reservoir (in microliters per minute) and the perfusion pressure (in millimeters of mercury). Three groups were studied: a 0-hour group, with AS perfused with DMEM 1 to 3 hours after enucleation; a 0-hour alb-group, with AS perfused with DMEM plus 0.1 mg/ml albumin 1 to 3 hours after enucleation; and a 24-hour group, with AS perfused after storage for 24 hours in DMEM. In the 0-hour groups, perfusion with increasingly hyposmotic or hyperosmotic media was also made in 30-minute steps, followed by a return to isosmotic medium for 90 minutes. RESULTS: Perfusion of AS with DMEM for 9 hours caused a progressive increase in C that was statistically significant at 225 minutes in the 0-hour group perfused with DMEM and at 195 minutes in the 24-hour group perfused with DMEM. The 0-hour alb-group perfused with DMEM did not show changes in C throughout the 9-hour perfusion period. Perfusion with increasingly hyposmotic media induced a progressive decrease in C that did not recover on return to isotonic medium. Hyperosmotic media caused a progressive increase in C that returned to control values when isotonic medium was again perfused. CONCLUSIONS: Preservation of tissue for C measurements is best achieved with short storage time (1 to 3 hours). Physiological concentrations of albumin (0.1 mg/ml) prevent development of washout, suggesting that albumin or an albumin-bound factor in aqueous humor may play a role in the maintenance of outflow resistance. Outflow facility also may be influenced by volume changes in the trabecular meshwork.

Human long-term bone marrow culture as a prognostic factor for hematopoietic reconstitution in autologous transplantation.

Human long-term bone marrow cultures allow persistence of hematopoietic stem cells in vitro for several weeks. Abnormalities in these cultures have been observed after cell treatment for purging in vitro. In autologous transplantation trials an increase in grafting failures after purging has also been reported. These results suggest a correlation between culture behaviour and graft kinetics. We analyzed the pattern of growth in Dexter culture of the bone marrow fraction infused in 52 patients with malignant diseases and subjected to autologous transplantation. In 23 cases, bone marrow cells had previously been treated in vitro with Asta-Z 7654 (n = 7) or with monoclonal antibodies plus complement (n = 16). Some of the long-term bone marrow culture parameters seemed to correlate with grafting kinetics, mainly adherent cell layer development and persistence of committed hematopoietic progenitors (CFU-GM) in the supernatant cells. The absence of a stromal layer defined a group with very poor hematological recovery after transplantation. Nine cases were included in this group and only one patient (11%) had recovered granulocytes and platelets. However, 90% of patients whose long-term cultures displayed normal adherent cell behavior had recovered peripheral hematological values. These results suggest that long-term bone marrow cultures could be used as a prognostic factor for hematopoietic reconstitution in autologous transplantation.

Enrichment of the fraction of nociceptive neurones in cultures of primary sensory neurones.

A method for enriching the fraction of nociceptive neurones in cultures of primary sensory neurones is described. Neurones from neonatal rat dorsal root ganglia were isolated, layered on 40% Ficoll and centrifuged, separating the neurones into a low density fraction (LDF) and a high-density fraction (HDF). The LDF had a smaller mean diameter (19.7 microm) than the HDF (27.3 microm) and uncentrifuged cells (23.6 microm). The proportion of cells immunoreactive for antibodies to substance P and calcitonin gene-related peptide, both of which are found in nociceptive neurones, was significantly greater in the LDF than in HDF. A substantial enrichment of the proportion of neurones responding to the algogenic substances capsaicin and bradykinin with an increase in intracellular calcium was observed in the LDF. The proportion of capsaicin and bradykinin-responsive neurones was also found to be increased by culturing the neurones, with a particularly pronounced enhancement in the proportion of bradykinin-responsive cells. We conclude that separation on the basis of density followed by culture is a useful way of enriching the proportion of nociceptive neurones for the purpose of electrophysiological, biochemical or other studies.

Facility changes mediated by cAMP in the bovine anterior segment in vitro.

The aim of this study was to investigate the influence of substances that increase intracellular cAMP levels on the aqueous humor outflow facility (C) of isolated bovine anterior segments. Anterior segments were perfused in vitro at a constant pressure of 10 mmHg for 270 min with a general protocol as follows: 90 min control perfusion with DMEM, 90 min of experimental perfusion with DMEM containing the test drug(s), and 90 min of postdrug-perfusion with DMEM. C was calculated as the ratio between the rate of medium inflow (microliter/min) and the perfusion pressure (mmHg). Anterior segments can be perfused in vitro for up to 5 hr without significantly modifying their C. The addition of epinephrine, forskolin, dibutyryl-cAMP or isobutylmethylxanthine to the control perfusion medium elicited a significant increase of C. If, during isobutylmethylxanthine perfusion, forskolin or epinephrine was added, C increased significantly. Finally, perfusion with indomethacin prior to addition of epinephrine prevented the increase of C induced by epinephrine. Epinephrine, the adenylate cyclase activator forskolin, the cAMP analog dibutyryl-cAMP, and the phosphodiesterase inhibitor isobutylmethylxanthine all increase aqueous facility. It seems reasonable to suspect that the cAMP system is involved in epinephrine's effects on bovine trabecular meshwork cells. Moreover, the complete inhibition by indomethacin of the outflow facility increase induced by epinephrine suggests that prostaglandins may be involved in the outflow facility mechanisms related to adrenoreceptor stimulation of trabecular meshwork cells.

Heparin cofactor II: a new marker for pre-eclampsia.

The plasma levels of heparin cofactor II were determined in pregnant women who were either normotensive, or had essential hypertension, gestational hypertension or pre-eclampsia during the third trimester and 72 h after delivery. Heparin cofactor II levels in the pre-eclampsia group were depressed. The clinical relevance of this finding is the potential utility of heparin cofactor II plasma levels in the differential diagnostic between non-proteinuric hypertension and pre-eclampsia.

Hepatic artery aneurysm: diagnosis by duplex-Doppler ultrasound. Case report.

A case of hepatic aneurysm diagnosed by duplex-Doppler US is reported. The demonstration of a complex hepatic hiliar mass with an arterial turbulent blood flow spectrum, permitted the diagnosis, which was confirmed by subsequent abdominal CT exploration. Our case confirms that duplex-Doppler US is useful non-invasive tool for the diagnosis of hepatic artery aneurysm.

Embryonic development of pineal gland vesicles: a morphological and morphometrical study in chick embryos.

Pineal cell aggregates in 5, 10 and 15 day-old chick embryos have been studied. Cell aggregates were classified into rosettes or vesicles and spheroid and ellipsoid vesicles distinguished. The number of pineal vesicles per unit of surface (vesicle density) was determined in three pineal portions: apical, anterior and posterior. By day 5, only cellular rosettes were found, mainly in the apical portion. After 10 and 15 days, the presence of rosettes was occasional. The posterior wall showed only small spheroid vesicles, while in the apical and anterior areas ellipsoid vesicles were also observed. Moreover, the spheroid/ellipsoid vesicle ratio increased from the 10th to the 15th day of incubation. The vesicle density decreased between the 10th and 15th day because of the increase in both vesicle and pineal size, without changes in the total number of vesicles. The results suggest that changes in vesicle morphology and density could be related to the functional activity of the pineal gland during embryonic development.

[Carotid atherosclerosis evaluated by two-dimensional ultrasonography in patients with primary hypercholesterolemia]. / Aterosclerosis carotídea evaluada por ecografía bidimensional en pacientes con hipercolesterolemia primaria.

BACKGROUND: Two-dimension ultrasonography permits to noninvasively quantify extracoronary atherosclerosis. The objective of this study was to assess preclinical atherosclerosis of the extracranial carotid arteries in patients with primary hypercholesterolemia. METHODS: Lipid and nonlipid cardiovascular risk factors were evaluated in 206 patients with dyslipidemia (127 men and 79 women, mean age 49 years, range 18-75), and a multifactorial cardiovascular risk profile was constructed for each patient. Ultrasound measurements of the intima-media thickness in the common carotid artery of each side were taken, and the number and height of any atheroma plaques present were quantified. RESULTS: Asymptomatic plaques were found in 120 patients (58%), and were more frequent in men than in women (65 vs 47%, p = 0.009), and in patients with than in those without prior coronary heart disease (80 vs 50%, p < 0.001). Both intimal thickening, indicative of early atherosclerosis, and the extent of arterial wall involvement with plaques, which represents an advanced stage of the disease, increased significantly with age and with increasing multifactorial cardiovascular risk, reflecting a positive relation between signs of atherosclerosis and the burden of risk factors. Intima-media thickness also increased with increasing plaque score, indicating the generalization of atherosclerosis. CONCLUSIONS: The high prevalence of preclinical carotid atherosclerosis confirms the atherogenic risk of primary dyslipidemias. The relation between carotid lesions and both coronary heart disease and multifactorial risk supports the validity of arterial ultrasound studies for cardiovascular risk prediction.

[Effects of percutaneous intrahepatic portosystemic shunt on splanchnic and systemic hemodynamics in patients with portal hypertension]. / Efectos de la derivación portosistémica percutánea intrahepática sobre la hemodinámica esplácnica y sistémica en pacientes con hipertensión portal.

Transjugular intrahepatic portosystemic shunt (TIPS) is a calibrated shunt directed at reducing the portal pressure gradient with a low incidence of hepatic encephalopathy and deterioration of hepatocellular function. The present study investigated the effects of TIPS on splanchnic and systemic hemodynamics on liver function and on the development of encephalopathy. A group of 30 patients treated with TIPS were included in the study: 26 patients with hepatic cirrhosis for an hemorrhagic episode by esophageal varices not controlled by medical treatment and sclerotherapy and in 4 cases with the Budd-Chiari syndrome for ascites refractory to medical treatment. Before, at 24 hours and 2 months after TIPS, the portal pressure gradient, cardiopulmonary pressure and cardiac output, blood flow of the azygos vein, and hepatic clearance of indocyanine green as indexes of liver function were determined. TIPS significantly decreased the portal pressures gradient and azygos blood flow. This was associated with a significant increase in cardiac output and a significant decrease in peripheral vascular resistance and hepatic clearance of indocyanine green. Portal flow deviated by TIPS was greater in the 9 patients (30%) who developed hepatic encephalopathy during follow up. In conclusion, TIPS effectively reduces portal hypertension. Nonetheless, it is associated with an increase in hyperdynamic circulation, a high incidence of encephalopathy and a deterioration in liver function.