Current Internal-medicine News Results

MicroRNA-151 and its hosting gene FAK (focal adhesion kinase) regulate tumor cell migration and spreading of hepatocellular carcinoma.

Hepatology. 2010 Sep; 52(3): 1162-4
Luedde T

Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma (HCC), but little is known about the functional non-coding sequences, particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic metastasis of HCC. We further show that miR-151, which is often expressed together with its host gene FAK, encoding focal adhesion kinase, significantly increases HCC cell migration and invasion in vitro and in vivo, mainly through miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading. Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus for tumour invasion and metastasis of HCC.

Effect of isolated fractions of Harpagophytum procumbens D.C. (devil's claw) on COX-1, COX-2 activity and nitric oxide production on whole-blood assay.

Phytother Res. 2010 Sep; 24(9): 1365-9
Anauate MC, Torres LM, de Mello SB

The present study evaluates the effect of isolated fractions of Harpagophytum procumbens (devil's claw) on cyclooxygenase (COX-1 and COX-2) activities and NO production using a whole blood assay. The activity of COX-1 was quantified as platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin E(2) production in LPS-stimulated whole blood. Total NO(2) (-)/NO(3) (-) concentration was determined by Griess reaction in LPS stimulated blood. Assays were performed by incubation of isolated fractions obtained by flash chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing different amounts of harpagoside with blood from healthy donors. Indomethacin and etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows that fraction containing the highest concentration of harpagoside inhibited indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and greatly inhibited NO production (66%). In contrast the fraction including iridoid pool increased COX-2 and did not alter NO and COX-1 activities. The fraction containing cinnamic acid was able to reduce only NO production (67%). Our results demonstrated that the harpagoside fraction is the main responsible for the effect of devils claw on these enzyme activities. However, other components from devil's claw crude extract could antagonize or increase the synthesis of inflammatory mediators. Copyright (c) 2010 John Wiley & Sons, Ltd.

An LC-MS method for simultaneous determination of nine ginsenosides in rat plasma and its application in pharmacokinetic study.

Biomed Chromatogr. 2010 Sep 1;
Zhou D, Tong L, Wan M, Wang G, Ye Z, Wang Z, Lin R

A sensitive and reliable LC-ESI-MS method for simultaneous determination of nine ginsenosides (Rh(1), Rg(2), Rg(1), Rf, Re, Rd, Rc, Rb(2) and Rb(1)) in rat plasma was developed and validated using saikosaponin A as an internal standard. The samples were extracted by solid-phase extraction. Chromatographic separation was carried out on a Hypersil Gold C(18) column (100 x 2.1 mm, 5 microm) by stepwise gradient elution with water (0.1% formic acid, v/v) and acetonitrile as the mobile phase. Detection was determined by selective ion monitoring mode using electrospray ionization in the negative ion mode. Good linearity over the investigated concentration ranges was observed with the values of r higher than 0.9900. The intra- and inter-day precisions were all no more than 15% and the average recoveries varied from 71.8 to 91.7%. This quantitative measurement was successfully applied to a pharmacokinetic study of Yi-Qi-Fu-Mai injection. Copyright (c) 2010 John Wiley & Sons, Ltd.

Digital clubbing in primary intestinal lymphangiectasia: a case report.

Wien Med Wochenschr. 2010 Aug; 160(15-16): 431-436
Wiedermann CJ, Kob M, Benvenuti S, Carella R, Lucchin L, Piazzi L, Chilovi F, Mazzoleni G

Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. The symptoms usually start in early infancy. We report a case of secondary hyperparathyroidism, osteopenia, monoclonal gammopathy and digital clubbing in a 57-year-old patient with a 12-year history of discontinuous diarrhea. Malabsorption with inability to gain weight, and finally weight loss and formation of leg edema were associated with protein-losing enteropathy. A low-fat diet associated with medium-chain triglyceride supplementation was clinically effective as medical management in reducing diarrhea and leg edema, and promoting weight gain. Double-balloon enteroscopy and small bowel biopsy histopathology confirmed dilated intestinal lacteals. Digital clubbing associated with primary intestinal lymphangiectasia which may causally be related to chronic platelet excess has not been reported before.

Mild to moderate functional tricuspid regurgitation: retrospective comparison of surgical and conservative treatment.

Cardiol Res Pract. 2010; 2010:
Smíd M, Cech J, Rokyta R, Roucka P, Hájek T

Background. Unoperated severe tricuspid regurgitation (TR) leads to the right ventricle (RV) failure. We wanted to determine if there was near-term postoperative progression of noncorrected mild to moderate functional TR in patients who underwent mitral valve surgery for chronic significant mitral regurgitation (MR) and if RV size and function were affected. Methods and Results. We compared two groups of patients retrospectively. In the first group (TVA+, n = 45), tricuspid valve annuloplasty (TVA) had been performed in conjunction with either mitral valve replacement (MVR) or mitral valve repair (MVP). The second group (TVA-, n = 22) underwent MVP or MVR without TVA. TVA+ group revealed a significant decrease in TR and right ventricle diameter. In the TVA- group, 7 patients (32%) showed a significant progression, by one or more grades, of noncorrected TR together with dilatation and decreased ejection fraction of the right ventricle. Conclusions. Tricuspid annuloplasty performed concurrently with MVP or MVR can prevent subsequent progression of tricuspid regurgitation along with right ventricular dilatation and systolic dysfunction in the near-term postoperative period.

Sleep and metabolism: an overview.

Int J Endocrinol. 2010; 2010:
Sharma S, Kavuru M

Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

Adult Onset Still's Disease and Rocky Mountain Spotted Fever.

Case Report Med. 2010; 2010:
Persad P, Patel R, Patel N

Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult female patients who presented with symptoms indistinguishable from that of classic childhood Still's Disease (Bywaters, 1971). George Still in 1896 first recognized this triad of quotidian (daily) fevers, evanescent rash, and arthritis in children with what later became known as juvenile inflammatory arthritis (Still, 1990). Adult Onset Still's Disease (AOSD) is an inflammatory condition of unknown etiology characterized by an evanescent rash, quotidian fevers, and arthralgias. Numerous infectious agents have been associated with its presentation. This case is to our knowledge the first presentation of AOSD in the setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have been suggested, the etiology of this disorder remains elusive. Nevertheless, infection may in fact play a role in triggering the onset of symptoms in those with this disorder. Our case presentation is, to our knowledge, the first case of Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF).

Premature Ventricular Contractions and Non-sustained Ventricular Tachycardia: Association with Sudden Cardiac Death, Risk Stratification, and Management Strategies.

Indian Pacing Electrophysiol J. 2010; 10(8): 357-71
Sheldon SH, Gard JJ, Asirvatham SJ

Premature ventricular contractions (PVCs) and non-sustained ventricular tachycardia (NSVT) are frequently encountered and a marker of electrocardiomyopathy. In some instances, they increase the risk for sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death. While often associated with a primary cardiomyopathy, they have also been known to cause tachycardia-induced cardiomyopathy in patients without preceding structural heart disease. Medical therapy including beta-blockers and class III anti-arrhythmic agents can be effective while implantable cardiac defibrillators (ICD) are indicated in certain patients. Radiofrequency ablation (RFA) is the preferred, definitive treatment in those patients that improve with anti-arrhythmic therapy, have tachycardia-induced cardiomyopathy, or have certain subtypes of PVCs/NSVT. We present a review of PVCs and NSVT coupled with case presentations on RFA of fascicular ventricular tachycardia, left-ventricular outflow tract ventricular tachycardia, and Purkinje arrhythmia leading to polymorphic ventricular tachycardia.

Expression and Localization of an Hsp70 Protein in the Microsporidian Encephalitozoon cuniculi.

Int J Microbiol. 2010; 2010:
Jolly CE, Leonard CA, Hayman JR

Microsporidia spore surface proteins are an important, under investigated aspect of spore/host cell attachment and infection. For comparison analysis of surface proteins, we required an antibody control specific for an intracellular protein. An endoplasmic reticulum-associated heat shock protein 70 family member (Hsp70; ECU02_0100; "C1") was chosen for further analysis. DNA encoding the C1 hsp70 was amplified, cloned and used to heterologously express the C1 Hsp70 protein, and specific antiserum was generated. Two-dimensional Western blotting analysis showed that the purified antibodies were monospecific. Immunoelectron microscopy of developing and mature E. cuniculi spores revealed that the protein localized to internal structures and not to the spore surface. In spore adherence inhibition assays, the anti-C1 antibodies did not inhibit spore adherence to host cell surfaces, whereas antibodies to a known surface adhesin (EnP1) did so. In future studies, the antibodies to the 'C1' Hsp70 will be used to delineate spore surface protein expression.

Low bone marrow oxygen tension and hypoxia-inducible factor-1alpha overexpression characterize patients with multiple myeloma: role on the transcriptional and proangiogenic profiles of CD138(+) cells.

Leukemia. 2010 Sep 2;
Colla S, Storti P, Donofrio G, Todoerti K, Bolzoni M, Lazzaretti M, Abeltino M, Ippolito L, Neri A, Ribatti D, Rizzoli V, Martella E, Giuliani N

Comment on 'Integrative genomic profiling of human prostate cancer'

Leukemia. 2010 Sep 2;
Bullinger L, Krönke J, Gaidzik V, Döhner H, Döhner K

Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials.

J Hum Hypertens. 2010 Sep 2;
Cicero AF, Gerocarni B, Laghi L, Borghi C

The oral assumption of lactotripeptides Valine-Proline-Proline (VPP) and Isoleucine-Proline-Proline (IPP) as nutraceuticals or functional foods is supposed to improve blood pressure (BP) control by angiotensin-converting enzyme-inhibition. However, data derived from clinical trials have reached conflicting conclusions. To perform a meta-analysis of placebo-controlled clinical trials evaluating the anti-hypertensive effect of lactotripeptides assumed as nutraceuticals or functional foods. Trials identified using a defined search strategy in PubMed were included in the meta-analysis, and their pooled effect was estimated with a random effects model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed. A total of 18 trials have been identified, the clinical data of which have been clearly reported. Pooled effect of peptides was a reduction of -3.73 mm Hg (95% CI: -6.70, -1.76) for systolic blood pressure (SBP) and 1.97 mm Hg (95% CI: -3.85, -0.64) for diastolic blood pressure (DBP). The effect was more evident in Asian patients (SBP=-6.93 mm Hg (95% CI: -10.95, -2.94); DBP=-3.98 mm Hg(95% CI: -5.38, -2.44)) than in Caucasian ones (SBP=-1.17 mm Hg (95% CI: -2.82, 0.72); DBP=-0.52 mm Hg (95% CI: -1.39, 0.13)), and apparently not related to age, baseline BP values, dose of lactotripeptides assumed or length of the treatment. VPP and IPP lactotripeptides assumed as functional foods may significantly reduce SBP particularly in Asian subjects. The relevance of this findings in other ethnicities or associated with different dietary pattern should to be further investigated.Journal of Human Hypertension advance online publication, 2 September 2010; doi:10.1038/jhh.2010.85.

Endoscopy: Risk assessment in upper gastrointestinal bleeding.

Nat Rev Gastroenterol Hepatol. 2010 Sep; 7(9): 480-2
Kuipers EJ

Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy.

Kidney Int. 2010 Sep 1;
Vuong MT, Hahn-Zoric M, Lundberg S, Gunnarsson I, van Kooten C, Wramner L, Seddighzadeh M, Fernström A, Hanson LA, Do LT, Jacobson SH, Padyukov L

The Fc-alpha receptor (FcalphaR/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis. No such difference was found in 42 patients with other renal diseases. The patients with IgAN without disease progression had stable but high levels of sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89 in the disease progression group. Moreover, levels of sCD89 complexes were correlated with one of the five CD89 genetic variants in 212 patients with IgAN and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377 was significantly associated with a lower expression of sCD89. However, no association between CD89 gene polymorphisms and susceptibility to IgAN was detected. Thus, we found an association between the levels of sCD89-IgA complexes in serum and the severity of IgAN, and a possible genetic component in regulating the production or expression of sCD89.Kidney International advance online publication, 1 September 2010; doi:10.1038/ki.2010.314.

Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals.

J Hypertens. 2010 Sep 1;
Delles C, Schiffer E, von Zur Muhlen C, Peter K, Rossing P, Parving HH, Dymott JA, Neisius U, Zimmerli LU, Snell-Bergeon JK, Maahs DM, Schmieder RE, Mischak H, Dominiczak AF

OBJECTIVES: We studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD. METHODS: Urine samples were analyzed by capillary electrophoresis coupled online to micro time-of-flight mass spectrometry. RESULTS: We defined a pattern of 238 CAD-specific polypeptides from comparison of 586 spot urine samples from 408 individuals. This pattern identified patients with CAD in a blinded cohort of 138 urine samples (71 patients with CAD and 67 healthy individuals) with high sensitivity and specificity (area under the receiver operator characteristic curve 87%, 95% confidence interval 81-92) and was superior to previously developed 15-marker (area under the receiver operator characteristic curve 68%, P < 0.0001) and 17-marker panels (area under the receiver operator characteristic curve 77%, P < 0.0001). The sequences of the discriminatory polypeptides include fragments of alpha-1-antitrypsin, collagen types 1 and 3, granin-like neuroendocrine peptide precursor, membrane-associated progesterone receptor component 1, sodium/potassium-transporting ATPase gamma chain and fibrinogen-alpha chain. Several biomarkers changed significantly toward the healthy signature following 2-year treatment with irbesartan, whereas short-term treatment with irbesartan did not significantly affect the polypeptide pattern. CONCLUSION: Urinary proteomics identifies CAD with high confidence and might also be useful for monitoring the effects of therapeutic interventions.

Predictors of clinical outcome after stent placement in atherosclerotic renal artery stenosis: a systematic review and meta-analysis of prospective studies.

J Hypertens. 2010 Sep 1;
Ronden RA, Houben AJ, Kessels AG, Stehouwer CD, de Leeuw PW, Kroon AA

OBJECTIVE: To determine clinical predictors for blood pressure and/or renal function improvement after renal artery stent placement in atherosclerotic renal artery stenosis (ARAS). METHODS: We searched PubMed, EMBASE and Cochrane databases for prospective studies investigating clinical predictive variables for renal function and/or blood pressure improvement after stent placement in ARAS. Eleven studies (1552 participants) were selected for our systematic review and meta-analysis. Meta-regression analysis was performed to investigate heterogeneity and to determine independent predictors for the outcome variables. Bias was evaluated by use of the Cochrane risk of bias tool. RESULTS: Multivariate meta-regression analysis showed no predictors for renal function improvement. High baseline diastolic blood pressure (DBP) and pulse pressure were significantly associated with the decrease in blood pressure after intervention. These results were consistent with the predictors reported by the individual studies. Meta-analysis showed a nonsignificant decline in serum creatinine of 4.7 mumol/l [95% confidence interval (Cl) -13.8 to 4.5]. Overall, systolic blood pressure (SBP) fell by 19.2 mmHg (95% Cl -22.7 to -15.7) and DBP decreased 8.9 mmHg (95% Cl -10.8 to -7.0). Risk of bias was present in the majority of the studies. CONCLUSIONS: The present review did not find a clinical characteristic that reliably predicts renal function outcome. High baseline pulse pressure predicted a smaller decrease in SBP after intervention and the best clinical predictor for a larger DBP reduction was a high pretreatment DBP.

Dialysis and Renal Transplantation in HIV-Infected Patients: a European Survey.

J Acquir Immune Defic Syndr. 2010 Aug 31;
Trullas JC, Mocroft A, Cofan F, Tourret J, Moreno A, Bagnis CI, Fux CA, Katlama C, Reiss P, Lundgren J, Gatell JM, Kirk O, Miró JM,

OBJECTIVES:: To determine prevalence and characteristics of end-stage renal diseases (ESRD) [dialysis and renal transplantation (RT)] among European HIV-infected patients. METHODS:: Cross-sectional multicenter survey of EuroSIDA clinics during 2008. RESULTS:: Prevalence of ESRD was 0.5%. Of 122 patients with ESRD 96 were on dialysis and 26 had received a RT. Median age was 47 years, 73% were males and 43% were black. Median duration of HIV infection was 11 years. Thirty-three percent had prior AIDS; 91% were receiving antiretrovirals; and 88% had undetectable viral load. Median CD4T-cell count was 341 cells per cubic millimetre; 20.5% had hepatitis C coinfection. Most frequent causes of ESRD were HIV-associated nephropathy (46%) and other glomerulonephritis (28%). Hemodialysis (93%) was the most common dialysis modality; 34% of patients were on the RT waiting list. A poor HIV control was the reason for exclusion from RT waiting list in 22.4% of cases. All the RT recipients were all alive at the time of the survey. Acute rejection was reported in 8 patients (30%). Functioning graft was present in 21 (80%). CONCLUSIONS:: This is the first multinational cross-sectional study of ESRD among European HIV population. Low prevalence of ESRD was found. Two-thirds of patients were excluded from RT for non-HIV/AIDS-related pathologies. Most patients had a functioning graft despite a high acute rejection rate.

Detection of HCV RNA in the Peripheral Blood Mononuclear Cells of Serum HCV RNA-Negative Egyptian Patients Under Interferon Treatment.

Am J Med Sci. 2010 Aug 31;
Zayed RA, Rushdy E, Saleh DA

INTRODUCTION:: Despite recent success after the introduction of combination therapy with interferon (IFN)-alpha and ribavirin, approximately 60% of patients with hepatitis C virus (HCV) genotype 4 fail to respond. Resistance to antiviral therapy remains a serious problem in the management of chronic hepatitis C. In most patients, HCV RNA could be detected in peripheral blood mononuclear cell (PBMC). OBJECTIVE:: The authors aimed to investigate the predictive value of HCV RNA in PBMC of patients with chronic hepatitis C after IFN treatment, which may act as the source of HCV reinfection of hepatic cells. METHODS:: Seventy patients with chronic hepatitis C were treated with IFN plus ribavirin for 48 weeks; they all achieved clearance of HCV RNA from serum. At the end of treatment, PBMC and serum were examined by real-time polymerase chain reaction for detection of HCV RNA. Six months later, HCV RNA in serum was monitored to detect sustained virologic response. RESULTS:: Analysis revealed the presence of detectable HCV RNA in the PBMC of 27% of patients despite clearance of serum HCV RNA. During follow-up, 80% of the patients who became serum HCV positive 6 months after the end of treatment had detectable level of HCV RNA in PBMC at the end of treatment. CONCLUSIONS:: The absence of HCV in the serum of patients by the end of treatment does not exclude future viremia. The patient might still be a source of infection to others. It is strongly encouraged to test for HCV in PBMC to detect lack of response to treatment and persisting infection.

Oxidative Stress Increased in Healthcare Workers Working 24-Hour On-Call Shifts.

Am J Med Sci. 2010 Aug 31;
Buyukhatipoglu H, Kirhan I, Vural M, Taskin A, Sezen Y, Dag OF, Turan MN, Aksoy N

INTRODUCTION:: Long work hours, night shifts, stressful situations and insufficient social support increase levels of anxiety and depression and decrease motivation to perform among healthcare professionals. In this study, we evaluated oxidative stress levels in medical residents working 24-hour on-call shifts, and in nurses, relative to non-healthcare hospital staff in sedentary positions. We also measured serum prolidase activity, a measure of collagen turnover, as an objective proxy for level of physical activity. METHODS:: Fifty-five male and 15 female medical residents on 24-hour, in-house, on-call duty, and 45 nurses and 30 (15 male/15 female) non-healthcare staff working 8-hour shifts were recruited. All were healthy nonsmokers. Parameters of oxidative stress and serum prolidase activity were measured twice for each subject, upon arising at 8 am after an overnight fast; and then again near the end of the work shift, or after 16 hours of consecutive work (at 12 pm) for residents. RESULTS:: After hours of continuous work, serum total oxidative status and the oxidative stress index increased significantly, whereas total antioxidant status decreased (all P < 0.0001) in healthcare staff (nurses, male and female residents). All these variables remained virtually unchanged in non-healthcare staff. Similarly, serum prolidase activity increased in healthcare staff (P < 0.0001), but failed to increase statistically in non-healthcare staff. CONCLUSIONS:: Healthcare workers suffer increased oxidative stress after prolonged work hours, especially while still on duty. Possible mechanisms for this include increased workload and, perhaps, psychological stress as well. However, long-term studies are needed to clarify the effects of sustained exposure to oxidative stress.

Syndrome of inappropriate secretion of antidiuretic hormone and rhabdomyolysis complicating rhytidectomy.

Plast Reconstr Surg. 2010 Sep; 126(3): 135e-6e
Peled M, Zack O, Zeltser D