P53 and Ki67 biomarkers as prognostic factors of non small cell lung carcinoma

Biomolecular behavior of tumor cells has become attractive to investigators. p53 as an oncosuppresor gene has been core of various studies and Ki67 is a nuclear protein involved in proliferation process. Stopping of onco-suppressor function theoretically allows proliferative system to get out of any control. In this case-control study we evaluated 50 patients with non small cell lung cancer, considering the association between P53 oncoprotein and Ki67 with rate of tumoral cells differentiation. We found the concurrent move of P53 and Ki67 according to the rate of differentiation and a significant risk (odds ratio) for being poorly differentiated in samples having higher rates of these two factors. We suppose that mutant P53 protein not only may be used as an objective finding for tumor grading, but probably as a practical point of approach for determining prognosis and planning therapy for this patients

Combination therapy with pulse cyclophosphamide plus corticosteroids improves renal outcome in patients with lupus nephritis

Background: The prognosis of SLE is influenced by the onset of glomerulonephritis. Clinical trials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management of lupus nephritis for preserving renal function. Objective: The purpose of this study is to define the outcome of renal function with bolus pulses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. Methods: In this open-label clinical trial, to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide, twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: 1) Induction with bolus methylprednisolone and cyclophosphamide. 2) Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3) Tapering with reduction of prednisolone by 10 each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4) Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms, urine protein excretion falling below 0.3 gr/dL or by at least 50, RBC cast disappearance, C3, C4, Hb, and ESR return to normal limits. Results: Twenty-three patients with lupus nephritis completed our therapeutic protocol. Renal biopsy was performed in 22 cases and indicated type IV in 20 patients (95.2), and type V in 2 patients. After an average of 4+1.95 months 22 patients achieved remission (95.65) and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant statistical differences were achieved between creatinine, proteinuria, hematuria, leukocyturia, urinary cast, C3, C4, ESR, and Hb before and after therapy (p<0.05). Plasma creatinine fell from 1.44+0.95 mg/dL to 0.97+0.78 (p<0.004). Proteinuria fell from 1879.78+1854.46 to 408.34+572.92 mg/24h (p<0.001). Thirteen episode of relapses were treated again with repeated cycles of cyclophosphamide and all remitted again. Conclusion: Intensive immunosuppression with steroid and cyclophosphamide provides excellent results with an acceptable rate of complications in the treatment of lupus nephritis

Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss

Background: Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents. Method: A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined. Results: The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Graphical Abstract: Pharmacokinetics of xanthomicrol in rats. © 2016 The Author(s)

Oesophageal cancer among the Turkomans of northeast Iran

A Caspian Littoral Cancer Registry survey in the early 1970s established northern Iran as one of the highest oesophageal cancer incidence regions of the world. To verify this, an oesophageal cancer survey was carried out between 1995 and 1997 in the Turkoman Plain at the southeastern corner of the Caspian Sea. Oesophageal balloon cytology screening was carried out on 4192 asymptomatic adults above age 30 years in one town and three adjoining villages with a total population of 20 392 people at risk. Oesophagoscopy was performed on 183 patients with abnormal cytological findings. The discovery of two asymptomatic small squamous cell cancers and one ‘carcinoma- suspect’ implied a prevalence ranging from 47.7 per 100 000 to 71.5 per 100 000. During a 1-year active surveillance, 14 patients were found with clinically advanced oesophageal squamous cell cancer, yielding age-standardized incidence rates of 144.09 per 100 000 for men and 48.82 per 100 000 for women. The very high frequency of oesophageal cancer reported for northern Iran 25 years ago stands confirmed. Differences in incidence rates, then and now, can be attributed to survey methods used and diagnostic criteria applied, but not to socioeconomic factors, which have remained relatively stable. Oesophageal balloon cytology is a practical method of mass screening for oesophageal cancer in Iran. © 2000 Cancer Research Campaig

Relationship between cortisol and physical performance in older persons

Objective: Hypercortisolism is associated with muscle weakness. This study examines the relationship between cortisol and physical performance in older persons. Design/patients: The study was conducted within the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a population-based sample of healthy older persons in the Netherlands. Data from the second (1995/1996) and fourth (2001/2002) cycle were used pertaining to 1172 (65-88 years) and 884 (65-94 years) men and women, respectively. Measurements: Physical performance was measured by adding up scores on the chair stands, tandem stand and walk test (range 0-12). In the second cycle serum total and calculated free cortisol were assessed; in the fourth cycle evening salivary cortisol was assessed. Regression analysis (stratified for sex, adjusted for age, body mass index, alcohol use, physical activity and region) was performed to examine the cross-sectional relationship between cortisol and physical performance. Results: Women with higher calculated free cortisol scored less well on physical performance (b = -0.28 per SD higher cortisol, P = 0.016), which was mainly explained by poorer performance on the tandem stand (OR = 1.32 for a lower score per SD higher cortisol, P = 0.003). Men with higher salivary cortisol scored less well on physical performance (b = -0.90 in the highest vs. the lowest quartile, P = 0.008), which was mainly explained by poorer performance on the chair stands and walk test (OR = 1.88, P = 0.020 and OR = 1.81, P = 0.027, respectively, in the highest vs. the lowest quartile). Conclusion: Physical performance is negatively associated with high cortisol levels in older persons. © 2007 The Authors

Long-Term Follow Up of Secundum Atrial Septal Defect Closure with the Amplatzer Septal Occluder

During the past 15 years, closure of a secundum atrial septal defect (ASD) has moved from a surgical to a percutaneous transcatheter approach. Few long-term studies of the efficacy and safety of closure of an ASD by an Amplatzer septal occluder (ASO) exist.To examine the long-term results of secundum ASD closure using the ASO, data on 94 patients who underwent secundum ASD closure with the ASO between 1998 and 2002 were available and reviewed. Data regarding residual shunt, chest pain, palpitations, arrhythmias, headaches, transient ischemic attacks, cerebrovascular accidents, and mortality were collected.Seven (7.4%) subjects had residual shunts immediately following ASO placement. During follow-up, 4 residual shunts closed for a complete closure rate of 97%. Eighteen (19%) patients reported chest pain during the follow-up period. Twenty-three patients (24%) reported palpitations during the follow up period, 7 were documented arrhythmias, including supraventricular tachycardia, atrial fibrillation, and premature ventricular beats. Migraine headaches were new-onset in 4 patients. Migraine cessation occurred in 2 patients after secundum ASD closure. One child died from a cerebral vascular event 18 months following device placement. Only 1 patient developed mild aortic insufficiency.These data indicate that for up to 120 months of patient follow-up, the ASO continues to be a safe device. Residual shunts and arrhythmias have low incidence post-ASO placement. Given the mortality in one high-risk patient, further investigation into anti-platelet therapy after device placement is warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78631/1/j.1747-0803.2009.00358.x.pd

Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes

Background: Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR. Methods: Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p &lt; 0.05. Results: There was a significant reduction in right ventricular volumes at 6 months post-ASD closure (RVEDV: 208.7 ± 76.7 vs. 140.6 ± 60.4 mL, p &lt; 0.0001) and RVEF was significantly increased (RVEF 35.5 ± 15.5 vs. 42.0 ± 15.2%, p = 0.025). There was a significant increase in the left ventricular volumes (LVEDV 84.8 ± 32.3 vs. 106.3 ± 38.1 mL, p = 0.003 and LVESV 37.4 ± 20.9 vs. 46.8 ± 18.5 mL, p = 0.016). However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure (pre-closure 110.5 ± 55.7 vs. post-closure 90.7 ± 69.3 mL, p = 0.019). Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant (84.5 ± 34.8 mL to 81.8 ± 44.2 mL, p = NS). Conclusion: ASD closure leads to normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures.Karen SL Teo, Benjamin K Dundon, Payman Molaee, Kerry F Williams, Angelo Carbone, Michael A Brown, Matthew I Worthley, Patrick J Disney, Prashanthan Sanders and Stephen G Worthle

Paternal Origins and Migratory Episodes of Domestic Sheep

Deng et al. show that domestic sheep harbor four Y chromosome lineages and early expansions of sheep were associated with the segregation of primitive and fat-tailed phenotypes as well as traits selected for different purposes

Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed

Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667–248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication