HU Group Research Articles

Role of coronary artery calcium score in prediction of coronary artery stenosis in symptomatic patients with suspected coronary artery disease

Introduction The coronary artery calcium (CAC) score has been proposed as an alternative approach for stratifying cardiovascular risk. Aim To assess the role of CAC score in prediction of coronary stenosis in symptomatic patients with intermediate probability for coronary artery disease (CAD). Patients and methods A total of 80 symptomatic patients with intermediate probability for CAD underwent thorough history taking and clinical examination. Computed tomographic (CT) scan was done for all patients. A total of 48 (60%) patients with CAC score less than 400 HU (group A) underwent CT angiography: 30 (62.5%) patients had significant coronary stenosis (SCS) and were referred to invasive coronary angiography (ICA), whereas 18 (37.5%) patients had no SCS. Overall, 32 (40%) patients with CAC score more than 400 HU (group B) were referred directly for ICA. Results ICA for 62 patients was performed: 30 (62.5%) patients were referred from group A, and all had SCS (100%), whereas 30 (93.7%) patients of 32 referred from group B had SCS. Using logistic regression analysis, CAC score was the only predictor of SCS (P=0.024). Receiver operating characteristic curve data revealed CAC more than 311.2 HU as a cutoff point for prediction of SCS, with specificity of 85.0%, sensitivity of 63.3%, and area under the curve of 74.7%. CT angiography sensitivity for detection of stenosis less than or equal to 50%, stenosis more than 50%, and stenosis more than 70% was 73, 62.5, and 94%, respectively; specificity of 96.8, 99.4, and 99.4%, respectively; and overall accuracy of 85.0, 81, and 96.9%, respectively, with negative predictive value to rule out SCS 99%. Conclusion CAC score is predictive for the presence of SCS in patients, with intermediate probability for CAD.

Effects of exposure to mild hyperbaric oxygen during unloading on muscle properties in rats.

This study investigated the effects of exposure to mild hyperbaric oxygen during unloading on the properties of the soleus muscle in rats, because exposure to mild hyperbaric oxygen enhances oxidative metabolism in cells and tissues. Therefore, exposure to mild hyperbaric oxygen should inhibit the unloading-induced degenerative changes in skeletal muscles. One group of 7-week-old male Wistar rats were unloaded by hindlimb suspension for 2weeks (HU, n = 12). A second group of age-matched rats were exposed to mild hyperbaric oxygen at 1317hPa with 40% oxygen for 3h a day during hindlimb suspension (HU + MHO, n = 12). A third group of age-matched rats without hindlimb suspension and exposure to mild hyperbaric oxygen were assigned as the controls (WR, n = 12). Soleus muscle weight (per body weight), succinate dehydrogenase (SDH) activity, and peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) mRNA levels were lower in the HU and HU + MHO groups than in the WR group, and these were higher in the HU + MHO group than in the HU group. The unloading-induced type shift from type I to type IIA fibers was inhibited by exposure to mild hyperbaric oxygen during unloading. It is concluded that the unloading-induced decrease in soleus muscle weight (per body weight) and type shift from type I to type IIA fibers in the soleus muscle were partially inhibited by exposure to mild hyperbaric oxygen during unloading.

Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.

Protective effects of Enterococcus faecium strain R30 on transformation of slow to fast fiber under inactive condition

Inactivity results in the transformation of slow to fast fiber and mitochondria dysfunction in skeletal muscle. PGC‐1α, a transcriptional factor, can prevent transformation of slow to fast fiber and the reduced oxidative enzyme activity in skeletal muscle. We have confirmed that Enterococcus faecium strain R30 (R30) activated muscle sympathetic nerve and increased blood flow in muscle capillary in our previous study. Several studies report that the increased blood flow induces nitric oxide synthase (eNOS) expression via shear stress, and eNOS expression regulates PGC‐1α protein expression. Also, the activated sympathetic nerve activity increased PGC‐1α protein expression via activation of adrenergic receptor. Therefore, we examined the hypothesis that R30 might prevent the transformation of slow to fast fiber and the reduced oxidative enzyme activity via PGC‐1α protein expression in skeletal muscle under inactive condition. Fifteen male Sprague‐Dawley rats aged 11 weeks old were divided into three groups, that is, 1) control (CON; n = 5), 2) 2 weeks hindlimb unloading (HU; n = 5), and 3) HU+R30 (HU+R30; n = 5). In the experimental periods, we administered orally to R30 (500 mg/kg/day) in the HU+R30 group, and the same amount of physiological saline in the CON and HU groups. After 2 weeks hindlimb unloading, type I fiber composition ratio, citrate synthase (CS) activity, eNOS and PGC‐1α protein expression level were measured. Type I fiber composition ratio and CS activity were significantly higher in the HU+R30 than in the HU group. The expression levels of eNOS and PGC‐1α protein in the HU+R30 group were significantly higher than in the HU group. These results indicate that R30 supplementation could increase the levels of eNOS and PGC‐1α expression in soleus muscle, and prevent the transformation of slow to fast fiber and the reduced oxidative enzyme activity under inactive condition.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dietary astaxanthin supplementation attenuates disuse-induced muscle atrophy and myonuclear apoptosis in the rat soleus muscle.

Extended periods of skeletal muscle disuse results in muscle atrophy and weakness. Currently, no therapeutic treatment is available for the prevention of this problem. Nonetheless, growing evidence suggests that prevention of disuse-induced oxidative stress in inactive muscle fibers can delay inactivity-induced muscle wasting. Therefore, this study tested the hypothesis that dietary supplementation with the antioxidant astaxanthin would protect against disuse muscle atrophy, in part, by prevention of myonuclear apoptosis. Wistar rats (8 weeks old) were divided into control (CT, n=9), hindlimb unloading (HU, n=9), and hindlimb unloading with astaxanthin (HU+AX, n=9) groups. Following 2weeks of dietary supplementation, rats in the HU and HU+AX groups were exposed to unloading for 7days. Seven-day unloading resulted in reduced soleus muscle weight and myofiber cross-sectional area (CSA) by~30 and~47%, respectively. Nonetheless, relative muscle weights and CSA of the soleus muscle in the HU+AX group were significantly greater than those of the HU group. Moreover, astaxanthin prevented disuse-induced increase in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei. We conclude that astaxanthin supplementation prior to and during hindlimb unloading attenuates soleus muscle atrophy, in part, by suppressing myonuclear apoptosis.

Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction.

BackgroundThis study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions.Material/MethodsAMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction.ResultsLeukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group.ConclusionsDecrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats.

English

This study was aimed to devise a theoretical formula for the mid-age of incidence (MAI) from the prevalence of age groups and to confirm its application. The formula was devised using the concept of lost years of health and then simulated. In the inhabitants’ survey, MAI was calculated from the prevalence of liver disease in the areas, and the main cause of disease was analyzed between those areas where MAI was lower than 2.5% of the distribution with significantly high prevalence (HL group) and those areas where MAI was higher than 2.5% of the distribution with significantly high prevalence (HU group). In the computer simulation, MAI was not much different or a little lower than the mid-age of occurrence. In addition, the sum of the incidence rates in the 1-year age groups approximately corresponded to the maximum prevalence within the age groups in the simulation. In the HL group, the main cause of liver disease was alcoholic liver injury; in the HU group, one cause was type C hepatitis, whereas for many others, it was advanced alcoholic liver injury. Thus, the HU and t HL groups were confirmed as active and quiescent areas, respectively. Investigating the cause or stage is considered to be useful in future studies. Key words: Mid-age of incidence (MAI), Lost years of health, chronic disease, prevalence, age specific prevalence.

Effects of ulinastatin administered at different time points on the pathological morphologies of the lung tissues of rats with hyperthermia.

Hyperthermia not only directly induces cell injury of body tissues, but also causes the body to release large amounts of inflammatory mediators and cells with extensive biological activities to induce a systemic inflammatory response and immune dysfunction. Thus, hyperthermia causes systemic inflammatory response syndrome, aggravating injuries to various organs. This study aimed to observe the effects of ulinastatin (UTI) administered at different time points on the cellular morphologies of the lung tissues of rats with systemic hyperthermia. A total of 40 male Sprague Dawley rats were randomly divided into five groups: The normal control group (C group), the hyperthermia group without medication (H group), the hyperthermia and UTI pre-treatment group (HU group), the group treated with UTI at 1 h after hyperthermia (HU1 group), and the group treated with UTI at 2 h after hyperthermia (HU2 group). The systemic hyperthermia rat model was established in a heating chamber with a biological oxygen supply. For the HU, HU1 and HU2 groups, UTI (5×104 U/kg) was administered at different time points. For the C and H groups, an equivalent volume of normal saline was administered. During heating, the respiratory frequency and rectal temperature were measured and recorded once every 30 min. After 2.5 h of heating, the wet/dry weight (W/D) ratio of the lung tissues of the rats was measured. Additionally, the cellular morphologies of the lung tissues were observed under light and electron microscopes. The respiratory frequencies and lung tissue W/D ratios of the rats in the various hyperthermia groups were significantly higher than those of the rats in the C group (all P<0.05). The respiratory frequencies and lung tissue W/D values of the HU and HU1 groups were significantly lower than those of the H group (all P<0.05). Under the light microscope, the bronchial surrounding tissues of the HU and HU1 groups were loose, and the majority of the pulmonary alveolar structures were normal; the H and HU2 groups presented a number of changes, including pulmonary interstitial hyperemia, alveolar epithelial swelling and emphysema. Under the electron microscope, it was observed in the type II epithelial cells of the pulmonary alveoli of the H group that the mitochondria were swollen, the cell ridges were shortened, the microvilli were thin and increased, and the alveolar wall was thickened. Also, an increased number of infiltrating neutrophils were visible. In addition, the type II epithelial cells of the HU2 group also presented these changes to different extents and the changes in the HU and HU1 groups were the mildest. These results indicate that the early application of UTI relieves edema and the extent of cell injury of the lung tissue in rats with systemic hyperthermia.

Impact of Different Indications for HU Listing of VAD Patients on Survival after Heart Transplantation

Purpose German allocation system prioritizes (“HU”) patients with complications (compl.) during VAD-support. The impact of “HU” indications on survival was evaluated. Methods and Materials We performed a retrospective chart analysis of all pts. Transplanted in “HU”-status. Results 01/2000-10/2012 932 HU-pts. (305 VAD/627 no VAD) received a HTx. Used were Syncardia TAH (60/19,7%), Thoratec BVAD (36/11,8%), DuraHeart LVAD (34/11,1%), Thoratec LVAD (28/9,2%), Novacor LVAD (26/8,5%), HeartMate II LVAD (25/8,2%), HeartWare LVAD (21/6,9%), Ventrassist (15/4,9%), TCI LVAD (14/4,6%) and others (46/15,1%). In the VAD infection group, reasons for death were rejection (7/10.8%), abdominal compl. (4/6.25), sepsis (4/6.2%) and MOF (2/3.1%), in the neurological compl. group rejection (3/8.3%), abdominal compl. (2/5,6%) and technical compl. (2/5,6%). In the technical failure group MOF (5/9.1%), neurological compl. (3/5.5%) and rejection (3/5.5%) occurred. Within the VAD-related compl.group MOF (5/13.5%) was predominant. In the right heart failure group reasons for death included MOF, tumor, sepsis and abdominal compl. (all 1/6.3%). The main causes of death for HU patients without MCS were sepsis (24/6.2%), graft rejection (16/4.1%), malignant tumors (10/2.6%), neurological compl. and MOF (both 8/2.1%). Worst outcomes occurred in the infection and neurological compl.group (p=0,026), especially in 2000-2006 with more frequent use of pulsatile VAD (p Conclusions VAD-infection and neurological compl.group had significantly higher mortality. In infection, neurological and technical compl.group mortality steadily increased until 5 years. Results improved with a lower rate of pulsatile VAD use. Mortality stratified for HU reason HU group 3 months (%) 1 year (%) 5 years (%) VAD infection (n=65) 6,2 14,3 38,8 VAD neurological compl. (n=36) 8,3 33,3 43,9 VAD technical problem (n=56) 17,9 19,6 30,2 VAD-related compl. (n=37) 13,5 27,7 27,7 VAD right heart failure (n=17) 12,5 27,3 27,3 VAD various indications (n=25) 8,3 27,8 27,8 no VAD (n=697) 1,6 18,8 27,0

Comparison of Primary Physician Patterns of and Attitudes on Emergency Department Use

This study aimed to compare physician viewpoints and clinic patterns between primary care providers (PCPs) with high patient emergency department (ED) use (HU) and PCPs with low patient ED use (LU). We conducted a mixed methods descriptive study of quantitative and qualitative data of 22 practices. We compared admission rates, American Academy of Pediatrics guideline adherence, efficiency, medical complexity, and patient satisfaction. Primary care provider interviews regarding ED use practices and perspectives were coded and inductively analyzed using Atlas 6.0 for themes. Compared with LU, the HU group had a higher admission rate (92 vs 41 admissions per 1000 members, P = 0.005), lower scores in adherence to American Academy of Pediatrics guidelines, and higher scores in satisfaction overall. There were no significant differences in efficiency, medical complexity, PCP communications, timeliness for appointment, satisfaction with after-hour care or likelihood of PCP referral. All PCPs described the EDs' purpose as for things they "cannot handle." The LU group was more likely to identify the ED for emergencies, whereas the HU group had a broader, more ambiguous definition of what they "cannot handle," with parental anxiety identified as a significant factor. In addition, the LU group recognized the need for more parental education about ED use. Primary care providers with low patient ED use were more likely to describe the EDs' purpose as being for emergencies and to recognize a need for more parental education about the use of the ED. All physicians struggled with reassuring parents.

Whole-body vibration and resistance exercise prevent long-term hindlimb unloading-induced bone loss: independent and interactive effects

Skeletal unloading induced by disuse or immobilization causes a decrease in bone mass and strength. We investigated the relationship between whole-body vibration (WBV) and resistance exercise (RE) in preventing bone loss induced by 8-week hindlimb unloading in young male rats. Sixty male Wistar rats were assigned randomly to 6 groups: age-matched control group (CON, n=10), hindlimb unloading group (HU, n=10), hindlimb unloading+standing group (HU+ST, n=10), hindlimb unloading+WBV group (HU+WBV, n=10), hindlimb unloading+RE group (HU+RE, n=10) and hindlimb unloading+WBV+RE group (HU+WBV+RE, n=10). After 8-week hindlimb unloading, micro-CT scanning and three-point bending test were performed in the femur. Sera were collected for analysis of bone formation and resorption markers. Compared with HU group, WBV, RE and the combination of WBV and RE (WBV+RE) significantly improved (P<0.01) one repetition maximum (1RM) (expressed as the percentage change from baseline, HU: -23%, HU+WBV: 21%, HU+RE: 48%, HU+WBV+RE: 51%), and maintained (P<0.05) cancellous volumetric bone mineral density (vBMD) and trabecular structure. No difference of cortical vBMD was found among all groups (P>0.05). WBV had no effects on biomechanical properties of the femur diaphysis (P>0.05). RE and WBV+RE significantly increased maximum load and cross-sectional moment of inertia of the femur diaphysis in hindlimb unloading rats (P<0.05). There was an interaction between WBV and RE in improving cancellous bone. These results demonstrate that WBV and RE interactively maintain cancellous structure and vBMD, and independently partially mitigate the reduction of bone strength in long-term hindlimb unloading rats.

Effect of homoharringtonine on bone marrow CD34 + CD117 + cells in patients with chronic myelogenous leukemia

This study investigated the effect of homoharringtonine (HHT) on bone marrow CD34 + CD117 + cells in patients with chronic myelogenous leukemia (CML). Fifty-seven patients with CML who could not receive either imatinib or interferon-α were treated with HHT (n = 31) or hydroxycarbamide (HU) (n = 26) to induce and maintain remission, and bone marrow CD34 + CD117 + cells were assayed with flow cytometry. The proportion of CD34 + CD117 + cells was higher in untreated patients (24.7 ± 6.4%) than in donors (4.4 ± 1.1%) and decreased remarkably in patients who had hematological remission (11.2 ± 3.1%) and cytogenetic response (8.9 ± 3.1%) as compared with those without (27.8 ± 7.3% and 18.5 ± 5.3%, respectively) at 12 months after therapy. The hematological remission rate for patients with proportion of CD34 + CD117 + cells ≥ 20% prior to treatment was lower (41.7%) than in patients with CD34 + CD117 + cells < 20% (78.9%; p < 0.05). However, there was no such difference of CD34 + CD117 + cell percentage in the HU group. It can be concluded that high expression of CD117 on CD34 + cells is a marker of poor prognosis and is also a target for the anti-CML effect of HHT.

What's Your Tanner? An Analysis of the Impact of Sickle Cell Disease Phenotype on Pubertal Development and Body Mass

Abstract 2123Little is known about the relative rate of pubertal development among children with different phenotypes of sickle cell disease (SCD). This study proposes, for the first time, to compare the influence of SCD phenotypes on pubertal development (PD) and body mass. We hypothesized that differences in pubertal development and body mass index (BMI) are modulated by SCD phenotype and treatment modality.We therefore conducted a cross-sectional study of SCD children and adolescents aged 8 – 18 years old (yo) to determine the impact of SCD phenotype and treatments on pubertal development (according to sexual maturity rating by Tanner stages, TS) and BMI. Participants were recruited from Children’s Healthcare of Atlanta and enrolled after written informed consent was obtained. Subjects’ age, height, weight, self-reported TS (via questionnaire), physician-reported TS, and major therapies were recorded. We investigated two major phenotypes, hemoglobin SC disease (SC, n= 16) and sickle cell anemia (SS, n=58). Within the SS group there were three treatment sub-groups, no-treatment (SS, n=18), hydroxyurea (S HU, n=21), and red blood cell transfusion (S Tx, n=19). Since age is associated with achieving a certain level of sexual maturity we divided the participants according to Nelson’s Textbook of Pediatrics. A Tanner stage of <3 in mid adolescence (14–16 yo) or <5 in late adolescence (17–18 yo) indicates delayed PD. Participants’ BMIs were placed in weight status categories according to CDC standards as follows: underweight (<5th percentile), normal weight (5– 85th percentile), and overweight/ obese (85–95th/ above 95th percentile). Results were corrected for gender and a non-parametric Mann-Whitney test was used to compare means.Early adolescent (10–13 yo) SS females had significantly lower self-reported TS, than those with SC (2±1 vs.3±1, means±SD respectively, p=0.018) or S Tx (3±0, p=0.031). Mid adolescent S HU females had significantly lower self-reported TS than SS (3±1 vs. 5±1, p=0.027) or SC (5±0, p=0.034), reflecting more past SCD complications in the S HU group. One late adolescent male in the Hb S Tx group did not attain Tanner 5. Across all groups, more than 50% of the remaining participants achieved normal PD (Table 1). Investigating BMI (kg/M2) by developmental stages revealed that early adolescent SC females had significantly higher BMI than S HU (23±9 vs. 16±1, p=0.036) and SS females (15±1, p=0.028). For early adolescent S Tx males, BMI was significantly higher than S HU males (19±1 vs.16±1, p=0.034). SS children were more likely than SC to be underweight (11–14%) regardless of treatment, and least likely to be overweight with no treatment (Table 2). [Display omitted] These results show that there are differences in level of maturity and BMI based on SCD phenotype and treatment modality. Differences seen in treatments are possibly due to the length of time on treatment modality prior to enrolling in study. Although these differences exist, the majority of participants lie within the normal PD range. Surprisingly, sickle cell disease, which is usually associated with delayed development, did not affect the ability of most these children to reach puberty within the expected timeframe. However, they still experienced lower than normal body mass. Lower BMI and slower puberty may be related to the number and severity of SCD complications, rather than hemoglobin phenotype alone. More studies are needed to better understand the effects of SCD severity and diet on somatic growth and puberty. Disclosures:No relevant conflicts of interest to declare.

Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time

To evaluate, in a longitudinal study, the profile of lipid peroxidation and antioxidant capacity markers in sickle cell anaemia patients receiving different treatments and medication over different time periods. The three groups were: patients undergoing transfusion therapy and receiving iron chelator deferasirox (DFX group, n = 20); patients receiving deferasirox and hydroxyurea (DFX + HU group, n = 10), and patients receiving only folic acid (FA group, n = 15). Thiobarbituric acid-reactive substance (TBARS) assays and trolox-equivalent antioxidant capacity (TEAC) assays were evaluated during two different periods of analysis, T0 and T1 (after ~388 days). Higher FA group TBARS values were observed compared with the DFX + HU group (p = 0.016) at T0; and at T1, higher FA group TBARS values were also observed compared with both the DFX group (p = 0.003) and the DFX + HU group (p = 0.0002). No variation in TEAC values was seen between groups, at either T0 or T1. The mean values of TBARS and TEAC for both the DFX and DFX + HU groups decreased at T1. The antioxidant effects of HU and DFX were observed by through an increase in TEAC levels in DFX and DFX + HU groups when compared with those of normal subjects. Increased TEAC values were not recorded in the FA group, and lipid peroxidation was seen to decrease after DFX and HU use.

Multidetector CT imaging of pleura: comparison of two contrast infusion protocols

Imaging of the pleura by multidetector CT (MDCT) can be challenging. There is no clear evidence or guidelines on contrast infusion parameters for imaging pleura. We compared two contrast protocols for assessing pleural pathology on MDCT. This was a prospective study in which consecutive patients with MDCT for suspected pleural disease on chest radiograph were randomised into two groups. The first group received 150 ml of intravenous contrast at a rate of 2.5 ml s(-1) and the second group received 100 ml at 2 ml s(-1). Images were acquired after a 60 s delay. Hounsfield units of the pleura, thoracic aorta, main pulmonary artery, portal vein and superior mesenteric artery were measured and analysed by two independent readers. 40 patients (20 in each group) who had pleural enhancement on MDCT were included for final analysis. The mean pleural enhancement value was 83 HU (Group A) vs 59 HU (Group B) (p = 0.0004). The mean aortic enhancement was 241 HU (A) vs 141 HU (B) (p<0.0001); main pulmonary artery enhancement was 208 HU (A) vs 139 HU (B) (p<0.0002); portal venous enhancement was 169 HU (A) vs 115 HU (B) (p<0.0001); and the superior mesenteric artery enhancement was 215 HU (A) vs 128 HU (B) (p<0.0001). Enhancement of the pleura and major vessels was significantly higher in the group receiving more contrast at a greater infusion rate. This technique of a single scan through the entire pleural surface with a delayed acquisition is promising. When pleural disease is suspected, contrast infusion protocols should be modified to achieve the best results and clinicians should be encouraged to specifically request a "pleural CT".

Effect of an aqueous extract of annatto (Bixa orellana) seeds on lipid profile and biochemical markers of renal and hepatic function in hipercholesterolemic rats

Annatto extract is a natural food color obtained from the outer coatings of the seeds of the Annatto tree (Bixa orellana L.). This is the first report in the literature that shows the relationship between the aqueous annatto extract and its influence on lipid profile in animals. Male Fisher rats were divided into three groups (n=12): C group, fed standard diet and water; H group, fed high-lipid diet and water and; HU group, with high-lipid diet and aqueous annatto extract for 60 days. The treatment with annatto extract in animals fed with the high-lipid diet lowered the LDL- and total cholesterol and raised the HDL-cholesterol, suggesting a hypocholesterolemic effect. Neither high-fat diet nor aqueous annatto extract had any significant effect on serum levels of albumin or serum activities of transaminases which suggested that no liver injury was induced.

Thermal preconditioning prevents fiber type transformation of the unloading induced-atrophied muscle in rats

Muscle atrophy is accompanied by a slow-to-fast transformation of the slow muscle, e.g., the soleus muscle, which is characterized by a decrease in the expression of the slow myosin heavy chain (MyHC) isoform. Heat stress before hindlimb unloading, i.e., thermal preconditioning, has been shown to reduce the rate of disuse-induced muscle atrophy. The present study examined whether thermal preconditioning could prevent a slow-to-fast transformation of the MyHC isoform through the induction of heat-shock protein (HSP) 72. Thermally preconditioned rats (Heat + HU) were individually placed in an environmentally controlled heat chamber for 1 h before hindlimb unloading for 2 weeks (HU). Although the mean fiber cross-sectional areas of the soleus muscle decreased in the HU and Heat + HU group, the loss of myofibrillar protein was attenuated in the Heat + HU group. Furthermore, a slow-to-fast transformation of MyHC isoform was inhibited in the Heat + HU group with the overexpression of HSP72. These results indicate that thermal preconditioning before hindlimb unloading attenuates the decrease of the slow MyHC isoform in the soleus muscle. Therefore, thermal preconditioning provides a new approach to prevent disuse-induced fiber type transformation of skeletal muscle.

Pulmonary Function in Children with Sickle Cell Anemia Following Treatment with Hydroxyurea.

Background: Pulmonary function is particularly susceptible to acute and chronic injury occurring in patients with sickle cell anemia (SCA). Acute Chest Syndrome (ACS), a common and potentially fatal complication of SCA, can be the cause or the consequence of abnormal pulmonary function (Siddiqui & Ahmed, 2003). Use of hydroxyurea therapy (HU) is increasing for children with recurrent pulmonary complications, following the findings that HU reduces risk of ACS in adults (Charache et al, 1995). How HU may improve pulmonary function in children with SCA is still ill-defined. The purpose of this study was to assess the change observed on serial pulmonary function tests (PFT) for children prescribed HU for abnormal pulmonary function.Methods: Over 240 children with pulmonary complications, such as acute chest syndrome, reactive airway disease, and chronic hypoxia, have been evaluated in the Sickle Cell Pulmonary Clinic at Children's Healthcare of Atlanta since beginning in July 2000. As part of the Clinic's standard of care, PFT were routinely attempted on children over the age of 5. A retrospective review of PFT results was done for the children with SCA and prior abnormal PFT. Children were included in the HU cohort (+HU) if repeat PFTs were available following > 3 months on HU therapy and if time on HU did not include frequent RBC transfusions. Children without history of HU therapy (−HU) were selected for comparison. PFTs were performed on a standard plethysmograph. Paired t-test was used to evaluate observed differences.Results: Thirty-one children with prior abnormal PFT had test before and following prescription of HU. Their mean age was 12.6 (range 6–20) years and mean duration of HU was 21 (range 4–47) months at the time of the repeat PFT. Hematologic changes expected on HU occurred for all 31 children. Twenty-four children followed for abnormal PFT had no history of HU (−HU) and matched the +HU group by gender, age (mean 12.3, range 7–19 years), duration followed at time of repeat PFT (mean 19, range 3–66 months; p=0.36), and initial hematologic parameters. Spirometry findings changed for +HU group, and remained stable for −HU group. Mean FVC and FEV1 values improved significantly on HU, when compared to initial (PreHU) PFT and to −HU controls. Conversion to a normal PFT, as interpreted by a pediatric pulmonologist masked to treatment status, occurred in 18 (58%) and 2 (8%) children in the +HU and −HU groups, respectively.Table 1: Serial PFT and hematologic parameters according to HU exposure−HU (n=24)+HU (n=31)InitialRepeat#PreHURepeatPFT parameter1TLC88 (13.6)285 (11.7)85 (13.4)90 (13.5)FVC78 (9.8)79 (9.9)75 (12.6)90 (13.2)*,++FEV175 (9.6)74 (12.2)72 (11.4)86 (10.2)*,++FEF25-7575 (22)72 (28.0)77 (23.4)79 (26.8)FEV1/FVC (%)85(6.7)82 (9.8)87 (11.8)86 (11.1)Pulse oximetry (%)95 (3.1)96 (2.4)94 (4.4)97 (2.8)*WBC (x103/ul)14 (3.8)13 (2.9)13.02 (2.9)9.0 (2.1) *,++Hb (g/dl)8.0 (0.1)8.0 (0.9)7.8 (1.1)9.1 (1.3) *,++MCV (fl)84 (9.2)85 (10.0)87.3 (8.1)101.2 (10.1) *,++HbF (%)4.3 (1.5)5.2 (5.2)6.0 (3.8)14.0 (7.3) *,++1 % predicted value for age, sex and height of subject.2Mean (SD)#No significant changes compared to Initial, p > 0.05.*P value < 0.001 compared to PreHU;++P value < 0.001 compared to −HU repeat.Conclusions: Serial PFTs showed improved pulmonary function, following initiation of HU therapy in children with prior abnormal PFT. Routine PFT assessments of children prescribed HU may serve as an objective measure of clinical response in children with SCA and pulmonary complications. These results will help in the design of future prospective studies examining the clinical benefits of HU therapy for children at risk for long-term pulmonary complications.

Prolonged Administration of Hydroxyurea Reduces Morbidity and Mortality in Adult Patients with Sickle-Cell Syndromes: Long-Term Experience of a Single Center.

Hydroxycarbamide (hydroxyurea; HU) is now considered as the main pharmacological agent capable to prevent the painful crises, to reduce the frequency and length of hospital admissions, and to improve the quality of life of patients with sickle-cell disease (SCD); whether HU can prevent the severe chronic complications or modify the mortality of these patients remains still an interesting unresolved question. The present study aims to evaluate the above effects of HU in a large number of SCD patients who received HU over long period of time and were followed in a single Center. To this effect, we evaluated the records of 330 patients with SCD who have been followed in the Thalassemia Center of Laikon Hospital over the last twenty years (136M/194F; median age: 42 years, range: 20- 76 years); 34 with homozygous HbS (SS) and 296 compound heterozygotes for HbS and beta-thalassemia. Of the latter, 131 patients had HbS/beta0-thal and 165 HbS/beta+-thal (107 with the IVSI-110 and 58 with the IVSI-6 thalassemic mutation). Administration of HU was started as early as 1991; progressively, the total number of patients who received HU reached 131 (“group A”); the remaining 199 were treated conventionally (“group B”). The mean age of the patients in the two groups was similar (mean ±SD: 43.3±9.9 years for group A and 44.1±12.6 years for group B) as well as the levels of HbF. The usual dosage of HU was 20 mg/kg/day, except for some patients, where toxicity or lack of effectiveness imposed modifications of the dosage in the range of 15 to 35 mg/kg/day. The median follow-up period was 8 years (range: 0.1–17 years) for the patients who received HU and 5 years (range: 0.1–18 years) for those who did not receive HU. Apart rare exceptions, patients reported every 4–8 weeks to the Outpatient Clinic, where they had a thorough clinical and laboratory evaluation, including FBC and reticulocytes, LDH, bilirubin, other basic biochemistries and HbF using conventional techniques. The percentage of HbS/HbS, HbS/beta0-thal, and HbS/IVSI-110 patients who were given HU was 70%, 49% and 40% respectively; in contrast, very few HbS/IVSI-6 compound heterozygotes had symptoms justifying use of the drug (3.6%). Patients receiving HU showed a dramatic reduction of the frequency of severe painful crises (from 7.4±6.5 episodes per year pre-HU to 0.2±0.4 episodes post-HU; p<0.001) along with a significant reduction of transfusion requirements (mean number of administered packed red cell units: 1.5±5.9 per year pre-HU diminishing to almost zero during HU treatment; p<0.001). These results led to a significant reduction of hospital admissions from 2.1±2.9 per year pre-HU to 0.06±0.02 per year post-HU (p<0.001). Moreover, we noticed a significant reduction of the frequency of chest syndrome from 6.1% pre-HU to 0.8% during the HU period (p=0.013). In contrast, we failed to observe any significant differences in the frequency of aseptic avascular necrosis (p=0.219) or cerebrovascular episodes among the patients who received and those who did not receive HU (p=0.65). Importantly, the death rate in the group of patients receiving HU was significantly lower than that observed among patients who were conventionally treated (12 deaths in group A vs. 47 in group B; 9.1% vs. 23.6%, respectively; p=0.001). The probability of 10-year survival was 91% for the patients treated with HU, while that of the patients conventionally treated was only 70% (Figure). This difference is further magnified if one considers that prior to starting HU the patients of group A had significantly higher transfusion requirements, frequency of painful crises, yearly number of admissions to hospital and intensity of hemolysis in comparison to the group of patients who were not given HU (p=0.004, <0.001, <0.001, and 0.01, respectively). Factors that predicted for a superior survival in the HU group include the increased level of total hemoglobin, a reduced platelet and leukocyte count, increased HbF levels, low reticulocyte counts and low bilirubin and serum LDH levels at 6 months post-HU administration. Side-effects of HU therapy were minimal, predictable and easily manageable. Our study provides evidence that, in addition to reducing the number of painful crises, the frequency of hospital admissions and the transfusion requirements, the long-term administration of HU in adult patients with sickle cell syndromes can improve survival. These results highlight the beneficial effect of HU in SCD and raise the issue of expanding the use of HU in all patients with these conditions. [Display omitted]

Efficacy of Anagrelide Compared with Hydroxyurea in Patients with Essential Thrombocythemia.

The essential thrombocythemia (ET) is characterized by thrombohemorrhagic risk. ET patients receiving HU and anti-aggregants show normal platelets but present platelet coagulant and endothelial aggregation. Anagrelide (ANA) is a platelet-lowering drug that inhibits platelet aggregation. Therefore, we evaluated platelets, platelet factor 4 (PF4), prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex (TAT) and d-dimer (DD) and von Willebrand factor (vWF) as markers of platelet coagulant and endothelial aggregation, respectively, in ET patients treated either with HU or ANA. All measurements were performed before treatment and when complete response, defined as platelet < 400 x109/L for more than 1 month, was achieved. Prolonged thrombocytosis causes thrombohemorrhagic risk. Hence, we investigated the cytoreduction time. The study comprised 36 patients (19 men, 17 women; mean age 65 years) who fulfilled PVSG and WHO. The mean duration of disease was 6 years. 17 patients received HU and 19 patients were on ANA. The average dose of HU was 0.5 g/d. ANA was initially administered at a dose of 0.5 mg/d. The dose was increased by 0.5 mg/d every week until the platelets had decreased to below 400 x 109/L. The average maintenance was 1.7 mg/d. All patients were on aspirin at dose of 100 mg/d and 50 mg/d in HU and ANA group, respectively. None of the patients had acquired or inherited thrombotic risk factors or had inherited coagulopathy. Eleven out of 17 HU patients (5 men, 6 women; mean age 68.6 years) developed thrombosis including six transient ischemic attack (TIA), three myocardial infarct (MI) and two deep venous thrombosis (DVT). The thrombosis occurred at a median time from diagnosis of 2 years. The ANA group did not experience thrombosis. Platelets were determined by automated analyser. PF4, F1+2, TAT and DD and vWF were assayed by ELISA and immunoturbidimetric assay, respectively. Before treatment, all patients had high platelets (1027±297 x 109/L) and elevated PF4, F1+2, TAT and DD (134±48 IU/mL vs 6±2 IU/mL, 3±2 nmol/L vs 0.6±0.2 nmol/L, 25±34 μg/L vs 2.7±1 μg/L, 224±172 μg/L vs 197±43 μg/L, respectively) (p< 0.0001, p<0.0001, p<0.0001 and p<0.0001, respectively) and low vWF (23±9% vs 102±30%) (p<0.0001). After treatment all patients had platelets <400 x 109/L (364 ±77 x 109/L), whereas PF4, F1+2, TAT and DD were higher (147±45 IU/mL, 3±2 nmol/L, 24±41 μg/L and 264±291 μg/L, respectively) and vWF was lower (34±9.9%) in HU group than controls (p<0.0001, p<0.0001, p<0.0001, p=0.001 and p<0.0001, respectively) and normal in ANA group (7±3 IU/mL, 1.1±0.8 nmol/L, 2.4±1.1 μg/L, 121±84 μg/L and 95±37%, respectively). The mean cytoreduction time was 3.2 and 1.8 months in HU and ANA group, respectively. A correlation there was between PF4 and F1+2 and TAT and DD and vWF (p=0.004, p=0.005, p=0.022 and p<0.0001, respectively). vWF did not correlate with F1+2, TAT and DD. Platelets did not correlate with thrombosis, whereas a correlation there was between PF4, F1+2, TAT and DD and thrombosis (p<0.0001, p=0.015, p=0.005 and p=0.034, respectively). A difference was observed in cytoreduction time between HU and ANA (p<0.0001). These results might support the superiority of ANA as antithrombotic drug besides its platelet-lowering effect.