bluuebunny/crossref_metadata_2025 huggingface dataset:
Raised natriuretic peptides, Big-endothelin-1 and improved beta-cell function in type 2 diabetic males with hyperuricaemia
Authors: Hermans Michel P. , Ahn Sylvie A. , Rousseau Michel F.
Published: July 2009

Urate, a naturally-occurring antioxidant, is a marker/factor for cardiovascular disease. Hyperuricaemia is associated with IR, MetS and endothelial dysfunction. We characterised the associations between neurohormones, uricaemia, and glucose homeostasis in type 2 diabetes mellitus (T2DM) males. Cross-sectional; 705 T2DM males divided into two groups: uric acid < 7.0 mg/dl (normouricaemic; n=476) versus uric acid ≥ 7.0 mg/dl (hyperuricaemic; n=229). HOMA beta-cell function (B), insulin sensitivity (S), hyperbolic product (B×S), and (B×S) loss rate were determined alongside neurohormones (Nt-proANP, BNP, Big ET-1 and UII). Mean age and diabetes duration were not different between groups. Hyperuricaemics had more macroangiopathy, total/central adiposity, IR, hypertension, dyslipidemia and MetS prevalence. Nt-proANP and BNP levels were more than twice as high in hyperuricaemics, whereas Big ET-1 and UII were higher by 46% and 14%, respectively. HOMA (B×S) was higher in hyperuricaemics: 31 (16)% vs. 26 (18)% (p=0.0004). B×S loss rate was faster in normouricaemics: 1.36 (0.54)% vs. 1.20 (0.43)%/year-1 (p<0.0001 ). The proportion with HbA1C < 7.0% was 39% (normouricaemics) vs. 49% (hyperuricaemics; p=0.0091). In T2DM males, hyperuricaemia is associated with raised neurohormones together with better beta-cell indices. Urate's dual properties may translate into beneficial (glucose homeostasis) and detrimental (raised neurohormones) effects.
Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus
Authors: Chis Irina C. , Ungureanu Marius I. , Marton Adriana , Simedrea Ramona , Muresan Adriana , Postescu Ion-Dan , Decea Nicoleta
Published: July 2009

In the present study we investigated the anti-hyperglycaemic and antioxidant effect of grape seed extract, a polyphenolic flavonoid, in normal and streptozotocin-induced diabetic Wistar rats. Adult male Wistar rats were divided into three groups: Group I: non-diabetic control; Group II: diabetic control; Group III: diabetic rats treated with grape seed extract, administered via an intragastric tube (0.6 ml/rat), at a dose of 100 mg/kg for 20 consecutive days after the induction of diabetes mellitus. Diabetes was induced by an i.p. injection with streptozotocin for groups II and III.TheTBARS, carbonylated proteins, were measured in the plasma and in the supernatant of liver homogenisates, and superoxide dismutase and catalase were measured in the haemolysates of RBCs and supernatant of liver homogenisates. The results showed that oral administration of grape seed extract (100 mg/kg/day) reduced the levels of lipid peroxides and carbonylated proteins and improved the antioxidant activity in plasma and hepatic tissue in rats treated with grape seed natural extract as compared with the diabetic control rats. These results suggested that the grape seed extract enhanced the antioxidant defence against reactive oxygen species produced under hyperglycaemic conditions, hence protecting the liver cells.
Review article: Thiazolidinediones and heart failure
Authors: Chaggar Parminder S. , Shaw Steven M. , Williams Simon G.
Published: July 2009

DM is an independent risk factor for the development of HF and its presence confers an adverse prognosis for those already diagnosed with HF.TZDs are potent insulin-sensitisers associated with a number of beneficial cardiovascular effects. However,TZDs increase renal sodium and water reabsorption, leading to fluid retention and overt signs of HF in patients with diabetes. Rosiglitazone has also been associated with an increased risk of myocardial infarction and cardiovascular mortality. However, pioglitazone may have macrovascular benefits. The majority of data on the cardiovascular safety of TZDs are based on non-cardovascular outcome trials and meta-analyses. Concerns regarding the risk of HF and cardiovascular safety of TZDs have led to restrictions on their use in patients with HF. This review addresses the latest evidence for HF with each of the TZD drugs currently available and reflects on the current guidelines regarding their prescription in at-risk patients.
Review article: Diabetes mellitus and heart failure — an overview of epidemiology and management
Authors: Baliga V. , Sapsford R.
Published: July 2009

Heart failure and Diabetes mellitus are chronic complex medical conditions that are closely related and commonly coexist.Treatment options have varied over the years, but newer treatment modalities have developed which have improved prognosis and longevity of patients with these conditions. Unfortunately, despite these advances, the evidence base remains insufficient, and larger randomised control trials need to be conducted. Here we discuss the available evidence and treatment and management of these inter-related conditions.
Review article: Left ventricular dysfunction and heart failure in metabolic syndrome and diabetes without overt coronary artery disease — do we need to screen our patients?
Authors: Roberts Aled W. , Clark Andrew L. , Witte Klaus K.
Published: July 2009

The metabolic syndrome and its components, glucose intolerance, T2DM, hypertension, dyslipidaemia and obesity are increasingly common. Patients with the metabolic syndrome have a higher prevalence of chronic heart failure (CHF) and, once diagnosed, CHF in such subjects is associated with a higher mortality than in those without this co-morbidity. However, early diagnosis of LV systolic dysfunction and symptomatic heart failure may prevent deterioration of heart failure and improve prognosis. The aim of this article is to summarise the prevalence of CHF in people with obesity, hypertension and T2DM, and to review how each co-morbid condition might predispose to and complicate the clinical diagnosis of CHF.
Can a chronic disease management pulmonary rehabilitation program for COPD reduce acute rural hospital utilization?
Authors: Rasekaba TM , Williams E , Hsu-Hage B
Published: July 2009

Chronic obstructive pulmonary disease (COPD) imposes a costly burden on healthcare. Pulmonary rehabilitation (PR) is the best practice to better manage COPD to improve patient outcomes and reduce acute hospital care utilization. To evaluate the impact of a once-weekly, eight-week multidisciplinary PR program as an integral part of the COPD chronic disease management (CDM) Program at Kyabram District Health Services. The study compared two cohorts of COPD patients: CDM-PR Cohort (4–8 weeks) and Opt-out Cohort (0–3 weeks) between February 2006 and March 2007. The CDM-PR Program involved multidisciplinary patient education and group exercise training. Nonparametric statistical tests were used to compare acute hospital care utilization 12 months before and after the introduction of CDM-PR. The number of patients involved in the CDM-PR Cohort was 29 (n = 29), and that in the Opt-out Cohort was 24 ( n = 24). The CDM-PR Cohort showed significant reductions in cumulative acute hospital care utilization indicators (95% emergency department presentations, 95% inpatient admissions, 99% length of stay; effect sizes = 0.62–0.66, P < 0.001) 12 months after the introduction of the CDM Program; in contrast, changes in the cumulative indicators were statistically insignificant for the Opt-out Cohort (emergency department presentations decreased by 5%, inpatient admissions decreased by 12%, length of stay increased by 30%; effect size = 0.14–0.40, P > 0.05). Total costs associated with the hospital care utilization decreased from $130,000 to $7,500 for the CDM-PR Cohort and increased from $77,700 to $101,200 for the Opt-out Cohort. Participation in the CDM-PR for COPD patients can significantly reduce acute hospital care utilization and associated costs in a small rural health service.
Cor pulmonale
Authors: Weitzenblum E , Chaouat A
Published: July 2009

The term “cor pulmonale” is still popular but there is presently no consensual definition and it seems more appropriate to define the condition by the presence of pulmonary hypertension (PH) resulting from diseases affecting the structure and/or the function of the lungs: PH results in right ventricular enlargement and may lead with time to right heart failure (RHF). Chronic obstructive pulmonary disease (COPD) is the first cause of cor pulmonale, far before idiopathic pulmonary fibrosis and obesity–hypoventilation syndrome. In chronic respiratory disease (CRD) PH is “pre-capillary,” due to an increase of pulmonary vascular resistance (PVR). The first cause of increased PVR is chronic long-standing alveolar hypoxia which induces pulmonary vascular remodeling. The main characteristic of PH in CRD and particularly in COPD is its mild to moderate degree, resting pulmonary artery mean pressure (PAP) in a stable state of the disease usually ranging between 20 and 35 mmHg. However, PH may worsen during exercise, sleep, and exacerbations of the disease. These acute increases in afterload can favor the development of RHF. A minority (<5%) of COPD patients exhibit severe or “disproportionate” PH (PAP >40 mmHg), the mechanism of which is not well understood. At present long-term oxygen therapy (LTOT) is the logical treatment of PH since alveolar hypoxia is considered to be the major determinant of the elevation of PAP and PVR. LTOT stabilizes or at least attenuates and sometimes reverses the progression of PH, but PAP seldom returns to normal. Vasodilators (prostacyclin, endothelin receptor antagonists, sildenafil, nitric oxide) could be considered in patients with severe PH but controlled studies in this field are presently lacking.
Providing reviews of evidence to COPD patients: controlled prospective 12-month trial
Authors: Harris M , Smith BJ , Veale AJ , Esterman A , Frith PA , Selim P
Published: July 2009

The aim of this study was to evaluate a novel patient-held manual designed to reduce the evidence–practice gap in chronic obstructive pulmonary disease (COPD). The intervention manual contained summaries of research evidence. It was developed using current best practice for patient information materials and designed to cause discussion of evidence between patient and doctor. A controlled before-and-after study was employed in two similar but geographically separate regions of metropolitan Adelaide, South Australia. Participants had moderate to severe COPD, with 249 included at baseline and 201 completing the study. Evidence-based COPD management was measured using an indicator with three components: rates of influenza vaccination, bone density testing, and pulmonary rehabilitation. A survey of behavioral steps leading to practice change was conducted with the trial. Analysis, by median split of socioeconomic disadvantage, showed significant difference between study arms for only one component of the indicator of evidence-based practice, enrolment in pulmonary rehabilitation and only for the most socioeconomically disadvantaged stratum. For both socioeconomic strata, more intervention participants than control participants reported remembering being given the information material, reading part or all, and finding it very or quite helpful. Other significant differences were restricted to the stratum of greatest socioeconomic disadvantage: reading all of the material, learning from it, referring back, and talking to a doctor about a topic from the material. Above 90% of all participants who received the manual reported reading from it, 42% reported discussing topics with a doctor, but only 10% reported treatment change attributable to the manual. We have found that people with COPD will read an evidence manual developed using current best practice. However, the study demonstrated improvement for only one of the three components of an indicator of evidence-based disease management for only the most socioeconomically disadvantaged stratum of participants. Future interventions should be designed to better translate reading uptake into evidence-based disease management.
Interviews as Experiments: Using Audience Effects to Examine Social Relationships
Authors: Cronk Lee , Gerkey Drew , Irons William
Published: July 2009

To explore the ability of audience effects to shed light on social dynamics, the authors contrasted responses given in individual and joint interviews. Interviews were conducted among the English-speaking residents of Utila, one of Honduras’s Bay Islands. Interviewees were older adults with at least one living adult child and younger adults with at least one living parent. Interviews were conducted with individuals alone and with pairs consisting of older adults and their adult children. The topic of the interviews was parenting, but the authors’ particular interest was in a question regarding obligations children have to their elderly parents. Responses to that question and to a control question were coded for length, interviewer behavior, vocalics, and forceful-ness of communicative style. Audience effects were found in children’s responses to the question about obligations to elderly parents: Children interviewed with parents responded more forcefully to that question than children interviewed alone. Responses to the control question showed no audience effect. Involvement in the island’s remittance economy was also associated with a more forceful communicative style, but this effect was not contingent on the audience present or the question asked. Audience effects may be a useful and important new tool for ethnographic research.
Internal Versus External Control of Reinforcement: A Review of the Locus of Control Construct
Authors: Kormanik Martin B. , Rocco Tonette S.
Published: July 2009

One aspect of personality, perceptions of internal versus external control of reinforcement, shifts under conditions of change.This review of the literature examines the relationship between planned organizational change and locus of control. The review includes literature from the disciplines of clinical and social psychology, adult development, education and learning theory, business and management, and human resource development (HRD). The discussion closes with implications for HRD theory building, research, and practice.
The Status of Equity for Hispanics in Public Higher Education in Florida and Texas
Authors: Perna Laura W. , Chunyan Li  , Walsh Erin , Raible Stephanie
Published: July 2009

This article uses descriptive analyses of data from the Integrated Postsecondary Education Data System to examine the status of equity for Hispanic students in public higher education institutions in Florida and Texas. The analyses show substantial inequities for Hispanics in enrollment, full-time faculty, and executive, administrative, and managerial staff. In both Texas and Florida, the greatest gaps in equity for Hispanics occur for full-time faculty and at the public flagship institutions.
The Influence of Total Plasma Homocysteine and Traditional Atherosclerotic Risk Factors on Degree of Abdominal Aortic Aneurysm Tissue Inflammation
Authors: Arapoglou Vassilis , Kondi-Pafiti Agathi , Rizos Demetrios , Kotsis Thomas , Kalkandis Christos , Katsenis Konstantinos
Published: July 2009

Objective: Modulating effects of genetic and environmental risk factors on severity of human abdominal aortic aneurysm (AAA) tissue inflammation remain unclear. We investigated the influence of total plasma homocysteine (tHcy) and traditional atherosclerotic risk factors (ARF) on degree of AAA tissue inflammation. Methods: Aneurysm specimens were obtained from 89 male patients aged 52 to 83 years, underwent asymptomatic not ruptured AAA (mean diameter 5.5 cm) open repair and graded for degree of histologic inflammation. Multivariate analysis was used to determine the association of tHcy and ARF, with degree of inflammation. Results: Current cigarette smoking, odds ratio (OR) 4.4, 95% confidence interval 1.3 to 15.2, P = .01 and no other ARF, neither tHcy levels OR 0.9 (0.9-1.02), P = .2 were associated with high-grade tissue inflammation. Conclusion: These results provide evidence against a major effect of tHcy levels on AAA tissue inflammation, while current cigarette smoking is a significant modulating factor.
Hypothenar Hammer Syndrome in a Computer Programmer: CTA Diagnosis and Surgical and Endovascular Treatment
Authors: Abdel-Gawad Ehab A. , Bonatti Hugo , Housseini Ahmed M. , Maged Ismaeel M. , Morgan Raymond F. , Hagspiel Klaus D.
Published: July 2009

Finger ischemia due to embolic occlusion of digital arteries resulting from trauma to the palmar ulnar artery has been termed hypothenar hammer syndrome (HHS). In HHS, arterial thrombosis and/or aneurysm formation with embolization to the digital arteries causes symptoms of ischemia. We describe a patient in whom the initial diagnosis was made on multidetector computed tomographic angiography (CTA), as well as his endovascular and surgical management.
Carotid Artery Pseudoaneurysm After Carotid Endarterectomy: Case Series and a Review of the Literature
Authors: Abdelhamid Mohamed F. , Wall Michael L. , Vohra Rajiv K.
Published: July 2009

Background: Pseudoaneurysm (PA) after carotid endarterectomy (CEA) is a rare complication with incidence less than 1%. There is a potential for rupture, embolization, thrombosis or compression of cranial nerves. Objective: We reviewed our experience and compare it to the literature to raise awareness of this rare though serious condition. It is crucial to treat these patients early to avoid the hazardous consequences. Methods: A review of the case records of patients who had CEA at University Hospital Birmingham (UHB) NHS Foundation Trust from 1990-2007, was undertaken. Information of patients including their aetiology, presenting features, treatment and results was collected. The English-language literature was searched using PubMed database for post CEA pseudoaneurysm. Results: Five patients developed post CEA PA. This represents 0.4% of the 1200 CEA performed at our hospital in the last 18 years. The timing of their presentation varied from three days to eight months after the original operation. All had patch reconstruction after CEA. Patches were intact at exploration of the PAs. There was one death and one stroke. The literature revealed 154 carotid PAs after CEA and two cases following carotid stenting 52 of these cases had infected PA. Patients with synthetic patches have the least incidence of infection. More than 80% had open surgery and 9% had endovascular repair. Conclusion: Post CEA surveillance is necessary to detect patients with PA early. Factors that favour infection must be avoided. Endovascular repair of carotid PA should be encouraged in specialised centres.
What Is Wrong in the Cava? A Rare Cause of Deep Vein Thrombosis
Authors: Deylgat Bert , Van Holsbeeck Bartel , Gellens Pat
Published: July 2009

When using cement in a hip arthroplasty, high intramedullary pressures are generated. This may lead to several complications, ranging from local extravasation to systemic complications such as the implantation syndrome. Until now, venous migration of cement after hip arthroplasty has never been associated with morbidity or mortality. We present a case in which cement pressurization lead to migration of cement up to the level of the inferior vena cava with subsequent deep vein thrombosis.
Photoplethysmography, an Easy and Accurate Method for Measuring Ankle Brachial Pressure Index: Can Photoplethysmography Replace Doppler?
Authors: Khandanpour Nader , Armon Matthew P. , Jennings Barbara , Clark Allan , Meyer Felicity J.
Published: July 2009

Objective: To assess the accuracy of ankle brachial pressure index (ABPI) assessed by photoplethysmography (PPG) compared with continuous wave Doppler (CW-Doppler). Methods: Ankle brachial pressure index was measured in a standard manner using both PPG and Doppler probes. For PPG-ABPI, a PPG probe was placed on the index finger and great toe, and a microcomputer determined the ABPI. These values were compared with the ABPI measured manually using an 8-MHz Doppler probe. Correlation and agreement between PPG and Doppler ABPI were assessed by Lin’s correlation coefficient and Bland—Altman plots. Results: In all, 133 claudicants were assessed. There was a strong correlation between the 2 ABPI methods (β = .79 and 95% limits of agreement of —0.23 to 0.24). Conclusion: Measuring ABPI automatically using the PPG technique is an effective alternative for Doppler ABPI. PPG-ABPI is completely objective, fast, and accurate.
Stent-Graft Placement for Management of Iatrogenic Hepatic Artery Branch Pseudoaneurysm After Liver Transplantation
Authors: Ginat Daniel T. , Saad Wael E. A. , Waldman David L. , Davies Mark G.
Published: July 2009

Pseudoaneurysm of the hepatic arteries is uncommon following liver transplantation and is usually iatrogenic. We describe a case of balloon angioplasty of a left hepatic artery stenosis complicated by an iatrogenic pseudoaneurysm. Resolution of the stenosis and the pseudoaneurysm was achieved through a combination of a bare stent and a balloon-expandable covered stent. The completion angiogram demonstrated excellent appearance of the patent hepatic arteries with exclusion of the pseudoaneurysm. No surgery was required. The graft and the patient did well for the following 6 months. Doppler ultrasound examination at 2 and 6 months postintervention revealed patent hepatic arteries and no evidence of the pseudoaneurysm.
Intermittent Roxithromycin for Preventing Progression of Small Abdominal Aortic Aneurysms: Long-Term Results of a Small Clinical Trial
Authors: Høgh Annette , Vammen Steen , Ostergaard Lars , Joensen Jette B. , Henneberg Esklid W. , Lindholt Jes S.
Published: July 2009

Background: Antibodies against Chlamydia pneumoniae are associated with an increased rate of expansion of small abdominal aortic aneurysms (AAAs). Short-term follow-up trials have shown a transient reduction AAA growth rate, in macrolide treated compared with placebo. Therefore we analysed the influence of intermittent, long-term roxithromycin treatment on AAA expansion and referral for surgery. Methods: Eighty-four patients with small AAAs were randomized to either an annual 4 weeks’ treatment with roxithromycin or placebo, and followed prospectively. Results: Intermittent, long-term Roxithromycin-treatment reduced mean annual growth rate by 36% compared with placebo after adjustment for potential confounders. Long-term roxithromycin-treated patients had a 29% lower risk of being referred for surgical evaluation, increasing to 57% after adjusting for potential confounders. Conclusion: Annual 4 week treatment with 300 mg roxithromycin daily may reduce the progression of small AAAs, and later need for surgical repair. However, more robust studies are needed for confirmation.
Carotid Artery Stenting for Stenosis Following Cervical Radiotherapy: Report of Early Failure With Associated Stent Fracture
Authors: Ross Charles B. , Khoobehi Ali , Irwin Chance L. , Dattilo Jeffrey B. , Naslund Thomas C.
Published: July 2009

Experience with carotid artery stenting (CAS) as an alternative to carotid endarterectomy (CE) for management of carotid stenosis continues to evolve. We report the case of a 64-year-old man who was treated with bilateral CAS for stenoses, which developed 7 years following thyroidectomy, neck dissection, and radiotherapy. Although long considered an ideal alternative to CE in this clinical setting, CAS in this case was complicated by multiple episodes of recurrent stenosis in his left carotid, managed by balloon angioplasty. Severe, early recurrence in his right carotid associated with a type III stent fracture was managed by CE. Close surveillance and intervention prevented neurologic morbidity. This case, combined with emerging published experience, argues for reappraisal of the general consensus that CAS is an ideal alternative to CE for radiotherapy-associated carotid stenoses.
Aortic Arch Resection and Ligation of the Descending Thoracic Aorta to Manage a Ruptured Thoracoabdominal Aneurysm
Authors: Weiss Aaron , Di Luozzo Gabriele , Etz Christian D. , Griepp Randall B.
Published: July 2009

Thoracoabdominal aortic aneurysms (TAAAs) are treated traditionally with open surgical repair; however, selective, high-risk patients can be evaluated for an endovascular approach. If the TAAA is complicated by the presence of aortic rupture, open surgical intervention is conventionally the course of action. However, unlike the primary operation, reoperations of TAAA might necessitate less conventional approaches. We report a patient with a previously repaired, ruptured, acute type B aortic dissection, who presents with a contained rupture of a TAAA.
Carotid Body Tumor Surgery: Management and Outcomes in the Nation
Authors: Vogel Todd R. , Mousa Albeir Y. , Dombrovskiy Viktor Y. , Haser Paul B. , Graham Alan M.
Published: July 2009

Objective: To evaluate the impact of carotid reconstruction (REC) and pre-operative embolization (EMB) for Carotid Body Tumor (CBT) surgery. Methods: Retrospective study utilizing the Nationwide Inpatient Sample (2002-2006). Results: 2117 patients (mean age 56.5 ± 17.2 years) underwent CBT surgery: 1686 excision alone (EX); 129 excision with embolization (EX+EMB); and 302 excision with carotid artery reconstruction (EX+REC). EX+REC compared to EX had greater rates of mortality (1.61%vs.0.59%; P =.0495), stroke (17.7% vs. 3.5%; P < .0002), and postoperative hemorrhage (43.1% vs. 2.4%; P < 0.002). EX+EMB did not demonstrate increased mortality or stroke compared to EX and the rate of postoperative hematoma was similar between groups (P = .3144). Conclusions: CBT resection is a relatively rare procedure and when combined with EMB was more expensive, but was associated with significantly fewer complications and decreased blood product utilization. These data suggest that CBT surgery requiring carotid reconstruction carries significant morbidity and that EMB as an adjunctive tool was beneficial for CBT surgery outcomes.
Primary Aortoenteric Fistula and Endovascular Repair
Authors: Jayarajan Senthil , Napolitano Lena M. , Rectenwald John E. , Upchurch Gilbert R.
Published: July 2009

Primary aortoenteric fistulae are difficult conditions to diagnose and manage. A 35-year-old male developed massive upper gastrointestinal hemorrhage due to a primary aortoduodenal fistula. Previous radiation therapy and retroperitoneal lymph node dissection for germ cell cancer with resultant dense retroperitoneal fibrosis made open aortic repair impossible. Endovascular balloon occlusion of the aorta and stent graft repair of the primary aortoduodenal fistula was performed. At 1-year follow-up, there is no clinical or radiographic evidence of stent-graft infection. Endovascular techniques and repair are important approaches to consider during the management of complicated primary aortoenteric fistulae when open surgical repair is not feasible.
Symptomatic 7-cm Abdominal Aortic Aneurysm in an Otherwise Healthy 31-Year-Old Woman
Authors: Moos John M. , Rowell Susan , Dawson David L.
Published: July 2009

Abdominal aortic aneurysms are rare in young women. We report the case of a 31-year-old woman who underwent open surgical repair of a symptomatic 7-cm abdominal aortic aneurysm (AAA). The patient had no identifiable AAA risk factors. Laboratory and pathological analyses demonstrated a nonspecific inflammatory component.
Diagnostic Strategies for the Persistent Sciatic Artery
Authors: Abularrage Christopher J. , Crawford Robert S. , Patel Virendra I. , Conrad Mark F.
Published: July 2009

Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that leads to aneurysmal degeneration and atherosclerotic changes. A careful understanding of the embryology is mandatory as variations in vascular development determine the optimal treatment. We present a case of an 85-year-old female who was incidentally found to have a PSA aneurysm, and review the literature.
The importance of bone marrow examination in determining complete response to therapy in patients with multiple myeloma
Authors: Chee Cheng E. , Kumar Shaji , Larson Dirk R. , Kyle Robert A. , Dispenzieri Angela , Gertz Morie A. , Colby Colin L. , Rajkumar S. Vincent
Published: July 2009

The current definition of complete response in multiple myeloma includes a requirement for a bone marrow (BM) examination showing less than 5% plasma cells in addition to negative serum and urine immunofixation. There have been suggestions to eliminate the need for BM examinations when defining complete response. We evaluated 92 patients with multiple myeloma who achieved negative immunofixation in the serum and urine after therapy and found that 14% had BM plasma cells more than or equal to 5%. Adding a requirement for normalization of the serum-free light chain ratio to negative immunofixation studies did not negate the need for BM studies; 10% with a normal serum-free light chain ratio had BM plasma cells more than or equal to 5%. We also found that, on achieving immunofixation-negative status, patients with less than 5% plasma cells in the BM had improved overall survival compared with those with 5% or more BM plasma cells (6.2 years vs 2.3 years, respectively; P = .01).
Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia
Authors: Russell Lisa J. , Capasso Melania , Vater Inga , Akasaka Takashi , Bernard Olivier A. , Calasanz Maria Jose , Chandrasekaran Thiruppavaii , Chapiro Elise , Gesk Stephan , Griffiths Mike , Guttery David S. , Haferlach Claudia , Harder Lana , Heidenreich Olaf , Irving Julie , Kearney Lyndal , Nguyen-Khac Florence , Machado Lee , Minto Lynne , Majid Aneela , Moorman Anthony V. , Morrison Heather , Rand Vikki , Strefford Jonathan C. , Schwab Claire , Tönnies Holger , Dyer Martin J. S. , Siebert Reiner , Harrison Christine J.
Published: July 2009

We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations.
Mer receptor tyrosine kinase is a novel therapeutic target in pediatric B-cell acute lymphoblastic leukemia
Authors: Linger Rachel M. A. , DeRyckere Deborah , Brandão Luis , Sawczyn Kelly K. , Jacobsen Kristen M. , Liang Xiayuan , Keating Amy K. , Graham Douglas K.
Published: July 2009

Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 80%. However, additional changes using available drugs are unlikely to provide significant improvement in survival. New therapies are warranted given the risk of severe therapy-associated toxicities including infertility, organ damage, and secondary malignancy. Here, we report ectopic expression of the receptor tyrosine kinase Mer in pediatric B-cell ALL. Inhibition of Mer prevented Erk 1/2 activation, increased the sensitivity of B-ALL cells to cytotoxic agents in vitro by promoting apoptosis, and delayed disease onset in a mouse model of leukemia. In addition, we discovered cross-talk between the Mer and mammalian target of rapamycin (mTOR) signaling pathways. Our results identify Mer as a novel therapeutic target in ALL and suggest that inhibitors of Mer will interact synergistically with currently used therapies. This strategy may allow for dose reduction resulting in decreased toxicity and increased survival rates. Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications.
Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time?
Authors: Delgado Julio , Milligan Donald W. , Dreger Peter
Published: July 2009

The development of reduced intensity conditioning regimens has increased the number of patients diagnosed with chronic lymphocytic leukemia that are referred for allogeneic hematopoietic cell transplantation (allo-HCT). However, given the toxicity of allo-HCT, it should only be offered to eligible patients whose life expectancy is significantly reduced by the disease. Accordingly, the European Group of Blood and Marrow Transplantation has recently identified those patients in whom allo-HCT could be a reasonable therapeutic approach. In this review, we have evaluated the outcome of chronic lymphocytic leukemia patients undergoing allo-HCT, either after conventional or reduced intensity conditioning regimens, in the context of current nontransplantation strategies. We have also analyzed the most important predisposing factors that might interfere with the procedure as well as posttransplantation complications that are particularly common in these patients. Finally, we have addressed the most relevant factors when deciding what patients should be considered for allo-HCT and the timing of the procedure.
Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner
Authors: Kottyan Leah C. , Collier Ann R. , Cao Khanh H. , Niese Kathryn A. , Hedgebeth Megan , Radu Caius G. , Witte Owen N. , Khurana Hershey Gurjit K. , Rothenberg Marc E. , Zimmermann Nives
Published: July 2009

The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5′-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase–dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65−/− mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner.
Mutagenesis of hexon “FX” hepatic tropism
Authors: Kremer Eric J.
Published: July 2009

In this issue of Blood, Alba and colleagues identify key amino acids in adenovirus hexon hypervariable regions that interact with coagulation factor X. By mutating these residues on the adenovirus's major capsid protein in Ad-based vectors, the authors succeed in retargeting gene transfer away from hepatocytes. The advances achieved in this study may create a vector platform that can be used to develop Ad-based therapeutics for nonliver-targeted diseases.
Bortezomib paradigm shift in myeloma
Authors: McConkey David J.
Published: July 2009

Bortezomib's unprecedented antitumor activity in myeloma has long been attributed to NF-κB inhibition. A new study from the group that put the drug on the map directly challenges this assumption.
Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush
Authors: Templeton Justin P , Nassr Mohamed , Vazquez-Chona Felix , Freeman-Anderson Natalie E , Orr William E , Williams Robert W , Geisert Eldon E
Published: July 2009

Background

Retinal ganglion cell (RGC) death is the final consequence of many blinding diseases, where there is considerable variation in the time course and severity of RGC loss. Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice.

Results

We found that RGCs are more susceptible to death following optic nerve crush in C57BL/6J mice (54% survival) than in DBA/2J mice (62% survival). Using the Illumina Mouse-6 microarray, we identified 1,580 genes with significant change in expression following optic nerve crush in these two strains of mice. Our analysis of the changes occurring after optic nerve crush demonstrated that the greatest amount of change (44% of the variance) was due to the injury itself. This included changes associated with ganglion cell death, reactive gliosis, and abortive regeneration. The second pattern of gene changes (23% of the variance) was primarily related to differences in gene expressions observed between the C57BL/6J and DBA/2J mouse strains. The remaining changes in gene expression represent interactions between the effects of optic nerve crush and the genetic background of the mouse. We extracted one genetic network from this dataset that appears to be related to tissue remodeling. One of the most intriguing sets of changes included members of the crystallin family of genes, which may represent a signature of pathways modulating the susceptibility of cells to death.

Conclusion

Differential responses to optic nerve crush between two widely used strains of mice were used to define molecular networks associated with ganglion cell death and reactive gliosis. These results form the basis for our continuing interest in the modifiers of retinal injury.
Citrus auraptene suppresses cyclin D1 and significantly delays N-methyl nitrosourea induced mammary carcinogenesis in female Sprague-Dawley rats
Authors: Krishnan Prasad , Yan Karen J , Windler David , Tubbs Jesse , Grand Robert , Li Benjamin DL , Aldaz C Marcelo , McLarty Jerry , Kleiner-Hancock Heather E
Published: July 2009

Background

Breast cancer is a major problem in the United States leading to tens of thousands of deaths each year. Although citrus auraptene suppresses cancer in numerous rodent models, its role in breast cancer prevention previously has not been reported. Thus, our goal was to determine the anticarcinogenic effects of auraptene against breast cancer.

Methods

The effects of auraptene on cell proliferation of MCF-7 and MDA-MB-231 human breast carcinoma cells in culture was assessed by measuring metabolism of a substrate to a formazan dye. Dietary effects of auraptene on tumor incidence, multiplicity and latency were studied in the N-methyl nitrosourea (MNU) induced mammary carcinogenesis model in female Sprague Dawley rats. The concentration of auraptene in rat tissues was analyzed by reverse phase HPLC. Cyclin D1 expression in MCF-7 cells and rat tumors was measured by western blot.

Results

Auraptene (500 ppm) significantly delayed median time to tumor by 39 days compared to the MNU only group (p < 0.05, n = 24–26). Auraptene (10 μM) reduced Insulin like Growth Factor-1 (IGF-1, 10 ng/mL)-induced cyclin D1 expression by 40% in MCF-7 cells. In comparison, western blot analysis of rat mammary tumors (n = 10 per group) confirmed that auraptene (500 ppm) significantly reduced (p < 0.05) cyclin D1 expression by 49% compared to the MNU only group. Analysis of rat mammary tissue extract by HPLC with fluorescence detection indicated an average concentration (means ± S.E.) of 1.4 ± 0.5 μM and 1.8 ± 0.3 μM in the normal mammary glands of the auraptene 200 ppm and 500 ppm groups, respectively. The concentration (means ± S.E.) of auraptene in the mammary tumors of the auraptene 200 ppm group was 0.31 ± 0.98 μM.

Conclusion

Overall, these observations suggest that the predominant effect of auraptene was to delay the development of tumors possibly through the suppression of cyclin D1 expression. These results point to the potential chemopreventive effects of auraptene in mammary carcinogenesis.
Malignant transformation of oral potentially malignant disorders in males: a retrospective cohort study
Authors: Ho Pei-Shan , Chen Pai-Li , Warnakulasuriya Saman , Shieh Tien-Yu , Chen Yun-Kwan , Huang I-Yueh
Published: July 2009

Background

Oral squamous cell carcinoma could be preceded by clinically evident oral potentially malignant disorders (OPMDs). Transformation of OPMDs to cancer has been studied in several population groups. It is difficult to undertake comparisons across populations due to variations in the methods of computation of malignancy rates among different studies. The aim of our study was to estimate the rate of malignant transformation of OPMDs taking into account the duration of follow-up and to identify the significant factors indicative of malignant potential.

Methods

A total of 148 male patients with OPMDs were included. They were selected among all consecutive subjects registered at the maxillofacial clinic at a medical hospital in Kaohsiung, Taiwan. The mean follow up period was 37.8 months.

Results

The malignant transformation rate was highest in subjects diagnosed with oral epithelial dysplasia. In this group the transformation rate was 7.62 per 100 persons-year. The rate in the group with verrucous hyperplasia (VH) was 5.21 per 100 persons-year, and in those with hyperkeratosis or epithelial hyperplasia was 3.26 per 100 persons-year. The anatomical site of OPMDs was the only statistically significant variable associated with malignancy. The hazard rate ratio (HRR) was 2.41 times for tongue lesions when compared with buccal lesions.

Conclusion

The reported discrepancies of malignant transformation of OPMDs involve the follow-up time to cancer development and hence it is preferable to use a time-to-event estimation for comparisons. We found that malignant transformation of OPMDs involving the tongue was significantly higher than in other anatomical subsites after adjusting for the clinicopathological type or lifestyle factors at diagnosis.
Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma
Authors: Eager Robert M , Cunningham C Casey , Senzer Neil N , Stephenson Joe , Anthony Stephen P , O'Day Steven J , Frenette Gary , Pavlick Anna C , Jones Barry , Uprichard Margaret , Nemunaitis John
Published: July 2009

Background

Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties.

Methods

This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m2 cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints.

Results

Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin.

Conclusion

Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.
Hydrogen bonding and packing density are factors most strongly connected to limiting sites of high flexibility in the 16S rRNA in the 30S ribosome
Authors: Huggins Wayne , Ghosh Sujit K , Wollenzien Paul
Published: July 2009

Background

Conformational flexibility in structured RNA frequently is critical to function. The 30S ribosomal subunit exists in different conformations in different functional states due to changes in the central part of the 16S rRNA. We are interested in evaluating the factors that might be responsible for restricting flexibility to specific parts of the 16S rRNA using biochemical data obtained from the 30S subunit in solution. This problem was approached taking advantage of the observation that there must be a high degree of conformational flexibility at sites where UV photocrosslinking occurs and a lack of flexibility inhibits photoreactivity at many other sites that are otherwise suitable for reaction.

Results

We used 30S x-ray structures to quantify the properties of the nucleotide pairs at UV- and UVA-s4U-induced photocrosslinking sites in 16S rRNA and compared these to the properties of many hundreds of additional sites that have suitable geometry but do not undergo photocrosslinking. Five factors that might affect RNA flexibility were investigated – RNA interactions with ribosomal proteins, interactions with Mg2+ ions, the presence of long-range A minor motif interactions, hydrogen bonding and the count of neighboring heavy atoms around the center of each nucleobase to estimate the neighbor packing density. The two factors that are very different in the unreactive inflexible pairs compared to the reactive ones are the average number of hydrogen bonds and the average value for the number of neighboring atoms. In both cases, these factors are greater for the unreactive nucleotide pairs at a statistically very significant level.

Conclusion

The greater extent of hydrogen bonding and neighbor atom density in the unreactive nucleotide pairs is consistent with reduced flexibility at a majority of the unreactive sites. The reactive photocrosslinking sites are clustered in the 30S subunit and this indicates nonuniform patterns of hydrogen bonding and packing density in the 16S rRNA tertiary structure. Because this analysis addresses inter-nucleotide distances and geometry between nucleotides distant in the primary sequence, the results indicate regional and global flexibility of the rRNA.
Bioassay guided purification of the antimicrobial fraction of a Brazilian propolis from Bahia state
Authors: Castro Myrella Lessio , Vilela Walquíria Ribeiro , Zauli Rogéria Cristina , Ikegaki Masaharu , Rehder Vera Lúcia Garcia , Foglio Mary Ann , de Alencar Severino Matias , Rosalen Pedro Luiz
Published: July 2009

Background

Brazilian propolis type 6 (Atlantic forest, Bahia) is distinct from the other types of propolis especially due to absence of flavonoids and presence of other non-polar, long chain compounds, but presenting good in vitro and in vivo antimicrobial activity. Several authors have suggested that fatty acids found in this propolis might be responsible for its antimicrobial activity; however, so far no evidence concerning this finding has been reported in the literature. The goals of this study were to evaluate the antibacterial activity of the main pure fatty acids in the ethanolic extract and fractions and elucidate the chemical nature of the bioactive compounds isolated from Brazilian propolis type 6.

Methods

Brazilian propolis type 6 ethanolic extract (EEP), hexane fraction (H-Fr), major fatty acids, and isolated sub-fractions were analyzed using high performance liquid chromatography (HPLC), high resolution gas chromatography with flame ionization detection (HRGC-FID), and gas chromatography-mass spectrometry (GC-MS). Three sub-fractions of H-Fr were obtained through preparative HPLC. Antimicrobial activity of EEP, H-Fr, sub-fractions, and fatty acids were tested against Staphyloccus aureus ATCC 25923 and Streptococcus mutans Ingbritt 1600 using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).

Results

EEP and H-Fr inhibited the growth of the microorganisms tested; nevertheless, no antimicrobial activity was found for the major fatty acids. The three sub-fractions (1, 2, and 3) were isolated from H-Fr by preparative HPLC and only sub-fraction 1 showed antimicrobial activity.

Conclusion

a) The major fatty acids tested were not responsible for the antimicrobial activity of propolis type 6; b) Sub-fraction 1, belonging to the benzophenone class, was responsible for the antimicrobial activity observed in the present study. The identification of the bioactive compound will improve the development of more efficient uses of this natural product.