bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Chronic Inflammation: Chronic Pancreatitis as a Risk Factor of Pancreatic Cancer
Authors: Dítě Petr , Hermanová Markéta , Trna Jan , Novotný Ivo , Růžička Miloš , Liberda Martin , Bártková Alice
Published: June 2012

Pancreatic carcinoma is a condition with late diagnosis and one for which there is no effective screening method. One possible diagnostic approach of so-called early adenocarcinoma is the identification and systematic examination of individuals at risk for this condition. Between 1992 and 2005 we systematically observed 223 individuals diagnosed with chronic pancreatitis. In this 14-year period we performed classical biochemical tests, endoscopic ultrasound, CT scans and ERCP. We also asked about the number of cigarettes smoked per year and classified individuals consuming regularly more than 80 g of alcohol per day for 5 years for men and 50 g of alcohol per day for 5 years for women as having the alcoholic form of chronic pancreatitis. The remaining patients were classified according to the TIGARO classification. Alcohol-related etiology was detected in 73.1% of patients, 21.5% had the chronic obstructive form and only 5.4% were classified as idiopathic pancreatitis. Pancreatic carcinoma was detected in 13 patients with chronic pancreatitis (5.8%), 3 patients were diagnosed with gastric carcinoma and 1 with esophageal carcinoma. Pancreatic malignancy developed mainly in patients with the alcoholic form of pancreatitis (4.5%). In the 14-year period 11 subjects died, out of which 8 cases were related to pancreatic carcinoma. Pancreatic and extrapancreatic cancer localized in the gastrointestinal tract are serious complications of chronic nonhereditary pancreatitis. Systematic observation of patients with chronic pancreatitis must be performed with the aim of early diagnosis of pancreatic malignancies (but also including other types).
Molecular Targeted Therapy in Hepatocellular Carcinoma: Present Achievements and Future Challenges
Authors: Giacomin Anna , Sergio Adriana , Vanin Veronica , Gazzola Alessia , Cazzagon Nora , Farinati Fabio
Published: June 2012

Therapeutic options in advanced stage hepatocellular carcinoma have been very poor until the discovery of new therapeutic agents that target the molecular pathways involved in hepatocarcinogenesis. In this paper we try to review the most important molecular agents in development, with a specific focus on sorafenib’s role and safety profile, especially in the treatment of patients with suboptimal liver function.
The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases
Authors: Lakatos Gábor , Hritz István , Varga Mária Zsófia , Juhász Márk , Miheller Pál , Cierny Gabriel , Tulassay Zsolt , Herszényi László
Published: June 2012

Background: It has been suggested that matrix metalloproteinases (MMPs) may play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, the impact of serum MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have scarcely been investigated in the same experimental setting in ulcerative colitis (UC) and Crohn’s disease (CD) as well as their correlation with IBD activity. Methods: MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 serum antigen levels were determined in 23 patients with UC, 25 patients with CD and 10 healthy control patients by enzyme-linked immunoassay technique. Statistical analysis with one-way ANOVA and Student’s t tests was performed. A linear regression analysis or a Spearman’s r test was used to assess correlation. Differences were considered significant with p < 0.05. Results: Serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly higher in UC and CD patients compared to controls. MMP-7 was also significantly higher in CD compared with controls. Elevated MMP-9 and TIMP-1 antigen levels showed significant positive correlation with disease activity of IBD. MMP-2 and TIMP-2 levels inversely correlated with CD activity. Significant correlations were found between MMP-9/TIMP-1 and MMP-2/TIMP-2 antigen levels in both UC and CD. Conclusions: We demonstrated that serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly increased in patients with UC and CD compared to controls. Our results suggest that MMPs and TIMPs may contribute to the inflammatory and remodeling processes in IBD. Serum MMP-9 and TIMP-1 might be useful as additional biomarkers in the assessment of IBD activity.
Role of DNA Methylation in Colorectal Carcinogenesis
Authors: Patai Árpád V. , Molnár Béla , Kalmár Alexandra , Schöller Andrea , Tóth Kinga , Tulassay Zsolt
Published: June 2012

Colorectal cancer is the most common malignancy of the gastrointestinal tract and a leading cause of cancer-related deaths worldwide. In order to detect early precursor lesions, colonoscopy is widely used. Unfortunately, patient adherence to colonoscopy is poor, which is partially due to the modest performance of currently used prescreening tests. Recently, epigenetics added an additional layer to the understanding of colorectal carcinogenesis. DNA methylation as part of the epigenetic gene-silencing complex is a universally occurring change in colorectal cancer and arises prior to the onset of recognizable preneoplastic changes, which may have huge preventive implications. Herein we discuss the major developments in the field of colorectal carcinogenesis and DNA methylation, including alterations in non-neoplastic conditions such as aging and ulcerative colitis. We try to demonstrate how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of colorectal cancer.
Isolated Colorectal Cancer Screening or Integrated Cancer Prevention? A Provocative Suggestion!
Authors: Stockbrugger Reinhold
Published: June 2012

Colorectal cancer (CRC) screening is still not fully established in the European Union. Recently, the United European Gastroenterology Federation (UEGF) supported CRC screening with the publication of quality guidelines and a written declaration in the European Parliament in favor of European-wide monitored CRC screening and primary prevention of CRC, the latter particularly in young citizens. In this article, the need for population-based CRC screening is once again stressed. In addition, the value of opportunistic CRC screening is pointed out, either as a regional or nation-wide alternative (such as in the USA and Germany) or as a ‘forerunner’ activity in view of subsequent population-based CRC screening. With regard to other parallel organ-related screening activities in Europe (breast, uterus) and the increasing need for primary prevention of malignant and benign diseases, the question is raised as to whether preventive activities should not be recognized as an integrated and logical part of a ‘healthcare chain’ offered to all European citizens.
New European Initiatives in Colorectal Cancer Screening: Budapest Declaration
Authors: Wittmann Tibor , Stockbrugger Reinhold , Herszényi László , Jonkers Daisy , Molnár Béla , Saurin Jean-Christophe , Regula Jaroslaw , Malesci Alberto , Laghi Luigi , Pintér Tamás , Teleky Béla , Dítě Petr , Tulassay Zsolt
Published: June 2012

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the ‘Budapest Declaration’ (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the ‘European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis’. The ‘Budapest Declaration’ together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU – the chance of equal access – be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.
Soft Tissue Tumors in Palaeopathology: A Review
Authors: Fornaciari Gino , Giuffra Valentina
Published: June 2012

Objective: To perform a review of soft tissue tumors in palaeopathology. Methods: Examination of palaeopathological literature. Results: Up to now, observations of neoplastic soft tissue lesions in mummified remains are limited to 15 cases, and only 4 of them present malignancies; 14 cases of calcified benign tumors, including 13 neoplasms of the female reproductive system and 1 teratoma, are also documented. Conclusions: The main reasons for the rarity of soft tissue tumors in palaeopathology, especially of malignancies, are apparently the short life span of past populations, the scarcity of mummified remains available in comparison with skeletal remains, and technical difficulties in the detection of neoplastic lesions in mummified tissues.
Evaluation of Prognosis for Carcinoma of Unknown Origin in Elderly Patients
Authors: Lu Hsueh-Ju , Chen Kuo-Wei , Tzeng Cheng-Hwai , Liu Jin-Hwang , Chiou Tzeon-Jye , Yen Chueh-Chuan , Chao Ta-Chung , Teng Hao-Wei , Chen Ming-Huang , Liu Chun-Yu , Wang Wei-Shu , Chang Peter Mu-Hsin , Yang Muh-Hwa
Published: June 2012

Purpose: Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site (CUP) for treatment considerations. Patients and Methods: Patients >70 years old with histologically proven carcinoma were retrospectively reviewed. The prognostic factors were analyzed with univariate and multivariate Cox regression. Results: We included 63 patients aged 70–79 years and 51 patients ≥80 years old. The results of multivariate Cox regression in the 70–79 years age group revealed white blood cell count ≤104/ml [p = 0.033; hazard ratio (HR) 2.51, range 1.079–5.840] and albumin ≥3.5 g/dl (p = 0.007; HR 3.38, range 1.398–8.177) as independent factors. In the group of patients ≥80 years old, Eastern Cooperative Oncology Group performance status <1 (p = 0.020), white blood cell count ≤104/ml (p = 0.001), albumin ≥3.5 g/dl (p = 0.006), lactate dehydrogenase (LDH) ≤250 U/l (p = 0.002) and non-chest metastasis (p = 0.043) were significantly better with univariate analysis. Multivariate Cox regression revealed albumin ≥3.5 g/dl (p = 0.007; HR 3.28, range 1.389–7.745) and LDH ≤250 U/l (p = 0.045; HR 3.18, range 1.026–9.848) as independent factors. Conclusions: For elderly patients with CUP, the serum albumin level seems to be a consistently independent prognostic factor. In patients >80 years old, serum LDH plays an important role in prognosis. This study is helpful in predicting the outcome and management for this group of patients.
Enzymatic Treatment of Whey Proteins in Cow’s Milk Results in Differential Inhibition of IgE-Mediated Mast Cell Activation Compared to T-Cell Activation
Authors: Knipping Karen , van Esch Betty C.A.M. , van Ieperen-van Dijk Adrie G. , van Hoffen Els , van Baalen Ton , Knippels Léon M.J. , van der Heide Sicco , Dubois Anthony E.J. , Garssen Johan , Knol Edward F.
Published: June 2012

Background: Cow’s milk (CM) hydrolysates are frequently used as milk substitutes for children with CM allergy. In hydrolysates, allergenic epitopes within CM proteins are diminished by enzymatic treatment. The aim of this study was to examine the allergenic and immunogenic properties of whey proteins during hydrolysis. Methods: During hydrolysis, samples were obtained at 0, 10, 15, 30, 45, 60, 75 and 90 min. Degradation was checked by HPLC and SDS-PAGE. Allergenic potential was analyzed by IgE crosslinking capacity of human Fcε receptor type 1-transduced rat basophilic leukemia cells sensitized with serum of CM-allergic patients. Whey-sensitized C3H/HeOuJ mice were ear challenged intracutaneously with the hydrolysates. Immunogenicity was tested using whey-specific human T-cell clones and T-cell lines at the level of proliferation and release of IL-4, IL-10, IL-13 and IFN-γ. Results: After 15 min of hydrolysis, the majority of the proteins were degraded. Hydrolysis for 15 min resulted in 92% inhibition of mast cell degranulation and in 82% reduction of ear swelling in the mouse model. In contrast, T-cell-stimulatory capacity was less affected by hydrolysis: reduction of human T-cell proliferation was only 9%. This was further reduced to 57 and 74% after 30 and 45 min of hydrolysis, respectively. Cytokine production followed the pattern of T-cell proliferation. Conclusion: Via differential analysis of allergenic versus immunogenic properties of the time kinetics of hydrolysis of whey proteins, we have demonstrated specific hydrolysis conditions with reduced IgE-crosslinking responses but retained T-cell activating properties. This approach might be useful in better defining CM hydrolysates.
Transferrin Polymorphism and Opportunistic Infections in HIV-Infected Women in Rwanda
Authors: Masaisa Florence , Gahutu Jean Bosco , Mukiibi Joshua , Delanghe Joris , Philippé Jan
Published: June 2012

Objective: We investigated the prevalence of opportunistic infections in HIV-infected women according to transferrin (TF) phenotype. Methods: We conducted a cross-sectional study among 200 HIV-positive women in the Butare University Teaching Hospital in Rwanda. TF phenotypes were determined using starch gel electrophoresis. Results: Phenotype frequencies of TF CD, CB and CC were 14.5, 3 and 82.5%, respectively. The homozygous TF DD phenotype was not found. Subjects with TF CD phenotype had a significantly higher prevalence of opportunistic infections than subjects with TF CC phenotype, 76 and 52%, respectively (p = 0.026). In logistic regression, there was a significant correlation between TF phenotypes and opportunistic infections (p = 0.012). Subjects with TF CD phenotype had significantly lower values for TF (p = 0.006) than TF CC subjects. Hematological parameters (RBC, RBC indices, hemoglobin, hematocrit, WBC, neutrophils, lymphocytes, platelets and erythrocyte sedimentation rate), iron, ferritin, TF saturation, C-reactive protein and CD4 count did not differ according to TF phenotype. Conclusion: Subjects with TF CC phenotype have a lower prevalence of opportunistic infections. Iron status may play a role in this association.
House Dust Mite-Specific Immunotherapy Alters the Basal Expression of T Regulatory and FcεRI Pathway Genes
Authors: Pevec Branko , Radulovic Pevec Mira , Stipic Markovic Asja , Batista Irena , Rijavec Matija , Silar Mira , Kosnik Mitja , Korosec Peter
Published: June 2012

Background: Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Methods: Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG4, nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Results: Decreased wheal sizes and VAS scores, negative challenges and increased sIgG4 levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Conclusions: Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3.
Imaging of Highly Malignant Osteosarcoma with Iodine-123-Vascular Endothelial Growth Factor
Authors: Holzer G. , Hamilton G. , Angelberger P. , Lai D. , Ubl P. , Dudczak R. , Dominkus M. , Li S.
Published: June 2012

Objective: Vascular endothelial growth factor (VEGF) is an important angiogenic factor, and its receptors have been shown to be overexpressed in various human carcinomas. In this study, we investigated the role of scanning with iodine-123 (123I)-labelled VEGF165 in patients with highly malignant osteosarcoma. Methods: Two patients (a 15-year-old female and a 14-year-old male) with osteosarcoma were injected with 140 MBq [<130 pmol (<5 µg) VEGF165 per patient] of 123I-VEGF165. Dynamic acquisition was initiated immediately after administration and carried out until 30 min after injection. Whole-body images were done in anterior and posterior views at various time points. All patients underwent single-photon emission tomography imaging. Results:123I-VEGF165 scans were positive in these patients. Sequential images clearly showed increased 123I-VEGF165 activity in osteosarcoma lesions. The tumour lesions were still visualized in whole-body images and single-photon emission tomography examinations 2 h after injection. Intravenous injection of 123I-VEGF165 did not cause any side effects. Conclusion: Our results suggest that 123I-VEGF165 receptor scintigraphy may be useful for the visualization of highly malignant osteosarcoma and/or metastasis and the angiogenic activity of the tumour.
Intermittent Chemotherapy Is a Treatment Choice for Advanced Urothelial Cancer
Authors: Onishi Takehisa , Sasaki Takeshi , Hoshina Akira
Published: June 2012

Objective: To investigate the potential benefit of intermittent chemotherapy, and to identify the eligibility criteria offering intermittent chemotherapy to patients with advanced urothelial cancer. Materials and Methods: Twenty patients who responded or had stable disease after receiving 3 cycles of induction chemotherapy (gemcitabine and cisplatin, or paclitaxel and carboplatin) were enrolled for a prospective study of intermittent chemotherapy. We evaluated for the duration of chemotherapy holiday, toxicity, quality of life (QOL), and overall survival. Results: The median number of cycles was 7 (range, 3–25). On resumption of treatment after the first chemotherapy holiday, 65% of the patients had partial response, 25% had stable disease, and 10% of the patients developed disease progression. The median duration of chemotherapy holiday was 22 weeks (range, 4–94), and the median chemotherapy holiday rate (CHR) was 0.53 (range, 0.25–0.86). The duration of the first chemotherapy holiday of more than 8 weeks significantly correlated to a high CHR. A response to induction chemotherapy, and normal levels of albumin and hemoglobin significantly correlated with a higher CHR. A significant improvement in fatigue, nausea and vomiting, and appetite loss was seen in the symptom scales of QLQ-C30 during the chemotherapy holiday. Conclusions: Intermittent chemotherapy is a feasible treatment strategy to balance disease control and QOL in selected patients.
Hyponatremia in Geriatric Inhospital Patients: Effects on Results of a Comprehensive Geriatric Assessment
Authors: Gosch Markus , Joosten-Gstrein Birgit , Heppner Hans-Jürgen , Lechleitner Monika
Published: June 2012

Objectives: To study whether geriatric patients with mild-to-moderate hyponatremia (≤131 mmol/l) reveal different outcomes in structured tests for functional and cognitive impairments, depression and malnutrition compared to normonatremic patients. Design: Single-center, retrospective case control study. Setting: The study was conducted in a Geriatric Evaluation and Management Unit of a Department for Geriatrics and Internal Medicine. Methods and Participants: We included 2,880 elderly patients (75.6% female, mean age 78.6 ± 6.98 years), consecutively admitted to the GEMU primarily or from another hospital or emergency department. Results were compared between a group of 129 patients with mild-to-moderate hyponatremia (118–131 mmol/l) and an age- and sex-matched control group of 129 patients with normal serum sodium values (>135 mmol/l). To assess functional and cognitive status, depression and malnutrition we used standardized tests of a geriatric assessment. Results: 16.7% (n = 477) of the total 2,880 patients were hyponatremic (≤135 mmol/l), 4.5% (n = 129) revealed moderate hyponatremia. Compared to the control group, these patients had significantly worse results in all tests of the Geriatric Assessment, including Activities of Daily Living, Mini Mental State Examination, Clock Completion Test, Geriatric Depression Score, Tinetti Mobility Test and the Timed Up&Go Test and the Mini Nutritional Assessment. Comorbidities were assessed by the Charlson Comorbidity Index and the Cumulative Illness Rating Scale with no significant difference between the two groups. The hyponatremic patients received significantly more medications than the normonatremic control group, but we could not find a significant difference with respect to the use of a distinct single drug therapy. Conclusion: We were able to demonstrate that geriatric patients with mild-to-moderate hyponatremia revealed a significantly worse outcome in all standardized tests of the geriatric assessment compared to a normonatremic control group. Serum sodium levels should therefore be considered when interpreting common tests of geriatric assessment.
Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: In vitro Susceptibility to Fosfomycin, Nitrofurantoin and Tigecycline
Authors: Al-Zarouni M. , Senok A. , Al-Zarooni N. , Al-Nassay F. , Panigrahi D.
Published: June 2012

Objective: To assess the susceptibility trends of community-acquired extended-spectrum β-Iactamase (ESBL)-producing urinary isolates with particular reference to fosfomycin, nitrofurantoin and tigecycline. Materials and Methods: Seven hospitals across the United Arab Emirates participated in this study from June 2008 to March 2010. The antibiotic sensitivity of ESBL-producing uropathogens to a panel of antibiotics including tigecycline, fosfomycin and nitrofurantoin was assessed. The Hyplex ESBL identification system (h-ES-ID) was used for genotypic identification. Results: Two hundred and ninety-two ESBL-producing Enterobacteriaceae isolates were identified during the study period. Of these, 182 (62%) were urinary isolates and comprised of Escherichia coli: 149 (81.9%), Klebsiella pneumoniae: 30 (16.5%) and Proteus mirabilis: 3 (1.6%). Of the 182 urinary isolates, 179 (98.3%) were from patients with community onset urinary tract infections. The h-ES-ID system identified 172 (94.5%) of the urinary isolates as CTX-M positive. All isolates were susceptible to imipenem and meropenem. Over half of the isolates showed resistance to gentamicin (98; 53.8%), trimethoprim-sulfamethoxazole (139; 76.4%) and ciprofloxacin (143; 78.6%). Sensitivity to nitrofurantoin and fosfomycin was 90 and 100%, respectively. Two CTX-M-positive K. pneumoniae isolates with tigecycline resistance (MIC >4 µg/ml) were identified. Conclusion: There is dissemination of CTX-M ESBL-producing urinary pathogens into the community. Fosfomycin and nitrofurantoin were active against ESBL-positive uropathogens, and emergence of tigecycline resistance needs close monitoring.
Relationship between Leptin Levels and Suppressed CD4 Counts in HIV Patients
Authors: Al-Fadhli Mariam , Saraya Mohammad , Qasem Jafar , Azizieh Fawaz , Shahab Shahab , Raghupathy Raj
Published: June 2012

Objective: To examine the relationship between serum leptin levels and suppression of CD4 count in HIV-infected individuals with highly active antiretroviral therapy (HAART). Subjects and Methods: Thirty seropositive HIV male patients selected from the Infectious Disease Hospital were classified into two groups according to their immunological and virological response to HAART. The first group included 15 male patients with low viral load and low CD4 counts; the second included 15 male patients with low viral load and high CD4 counts. Morning serum leptin and tumor necrosis factor-α levels of HIV patients were measured and correlated with fasting serum insulin, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HIV viral load and CD4 count. Results: Serum leptin levels were significantly higher in patients with high CD4 counts than in patients with low CD4 counts (mean serum leptin level 47.3 vs. 10.9 ng/ml, respectively; p < 0.0001). A positive correlation was observed between serum leptin levels and CD4 counts (r = 0.697; p < 0.0001); positive correlations were also seen between leptin levels and fasting serum insulin and HOMA-IR (r = 0.633, p < 0.0001, and r = 0.537, p < 0.003, respectively). Conclusion: Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery.
Reflectance Confocal Microscopy for the Evaluation of Solitary Red Nodules
Authors: Moscarella Elvira , Zalaudek Iris , Agozzino Marina , Vega Hernando , Cota Carlo , Catricalà Caterina , Argenziano Giuseppe , Ardigò Marco
Published: June 2012

The correct assessment of a solitary red nodule in clinical practice is of crucial importance, amelanotic melanoma being the most important differential diagnosis. Dermoscopy is nowadays a pivotal tool in the management of skin tumors, however it has some limitations in the evaluation of nonpigmented lesions, in which the diagnosis is merely based on the evaluation of the vascular pattern. Recently, reflectance confocal microscopy has been introduced as a new, noninvasive technique for the diagnosis of skin lesions. Confocal microscopy provides skin imaging in vivo at cellular level resolution, close to conventional histology. We present a series of clinical scenarios of red nodules, including melanoma metastasis, pyogenic granuloma, eccrine poroma, Spitz nevus and dermatofibroma. Reflectance confocal microscopy examination added important information to the clinical diagnosis and subsequent management in all cases except for dermatofibroma. We discuss the advantages and limitations of this technique in this particular field of application.
Patterns of Use of Perioperative Angiotensin-Converting Enzyme Inhibitors in Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass
Authors: Drenger Benjamin , Fontes Manuel L. , Miao Yinghui , Mathew Joseph P. , Gozal Yaacov , Aronson Solomon , Dietzel Cynthia , Mangano Dennis T. ,   the Multicenter Study of Perioperative Ischemia Research Group
Published: June 2012

Background—

Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of angiotensin-converting enzyme inhibitors (ACEIs) in coronary artery bypass graft surgery has been erratic and controversial.

Methods and Results—

This is a prospective observational study of 4224 patients undergoing coronary artery bypass graft surgery. The cohort included 1838 patients receiving ACEI therapy before surgery and 2386 (56.5%) without ACEI exposure. Postoperatively, the pattern of ACEI use yielded 4 groups: continuation, 915 (21.7%); withdrawal, 923 (21.8%); addition, 343 (8.1%); and no ACEI, 2043 (48.4%). Continuous treatment with ACEI versus no ACEI was associated with substantive reductions of risk of nonfatal events (adjusted odds ratio for the composite outcome, 0.69; 95% confidence interval, 0.52–0.91;
P
=0.009) and a cardiovascular event (odds ratio, 0.64; 95% confidence interval, 0.46–0.88;
P
=0.006). Addition of ACEI de novo postoperatively compared with no ACEI therapy was also associated with a significant reduction of risk of composite outcome (odds ratio, 0.56; 95% confidence interval, 0.38–0.84;
P
=0.004) and a cardiovascular event (odds ratio, 0.63; 95% confidence interval, 0.40–0.97;
P
=0.04). On the other hand, continuous treatment of ACEI versus withdrawal of ACEI was associated with decreased risk of the composite outcome (odds ratio, 0.50; 95% confidence interval, 0.38–0.66;
P
<0.001), as well as a decrease in cardiac and renal events (
P
<0.001 and
P
=0.005, respectively). No differences in in-hospital mortality and cerebral events were noted.

Conclusions—

Our study suggests that withdrawal of ACEI treatment after coronary artery bypass graft surgery is associated with nonfatal in-hospital ischemic events. Furthermore, continuation of ACEI or de novo ACEI therapy early after cardiac surgery is associated with improved in-hospital outcomes.
Influenza Vaccination and Major Adverse Vascular Events in High-Risk Patients
Authors: Johnstone Jennie , Loeb Mark , Teo Koon K. , Gao Peggy , Dyal Leanne , Liu Lisheng , Avezum Alvaro , Cardona-Munoz Ernesto , Sleight Peter , Fagard Robert , Yusuf Salim
Published: June 2012

Background—

We sought to determine the association between influenza vaccination and major adverse vascular events because the association remains uncertain.

Methods and Results—

A total of 31 546 participants were enrolled from 40 countries. Eligibility included age ≥55 years and known vascular disease. The primary outcome was a composite of death resulting from cardiovascular causes, myocardial infarction, or stroke during 4 influenza seasons (2003–2007). Influenza vaccination was associated with a lower risk of the outcome during 3 influenza seasons (defined using World Health Organization FluNet reports): 2004 to 2005 (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.50–0.77), 2005 to 2006 (adjusted OR, 0.69; 95% CI, 0.53–0.91), and 2006 to 2007 (adjusted OR, 0.52; 95% CI, 0.42–0.65), the same years that circulating influenza matched the vaccine antigen. In 2003 to 2004, there was an incomplete match between circulating influenza and the vaccine antigen, and there was no association between influenza vaccination and the outcome (adjusted OR, 0.96; 95% CI, 0.73–1.27). However, tests of potential biases in the analyses revealed associations between influenza vaccination and outcome during noninfluenza seasons except 2003 to 2004. The summary ORs in the influenza season (OR, 0.65; 95% CI, 0.58–0.74]) and noninfluenza season (OR, 0.66; 95% CI, 0.57–0.76) were almost identical. The reduction in risk of noncardiovascular death associated with the influenza vaccine ranged from 73% to 79%.

Conclusion—

Although initial analyses suggest that influenza vaccination was associated with reduced risk of major adverse vascular events during influenza seasons when the influenza vaccine matched the circulating virus, sensitivity analyses revealed that risk of bias remained. A randomized trial is needed to definitively address this question.
Childhood Physical, Environmental, and Genetic Predictors of Adult Hypertension
Authors: Juhola Jonna , Oikonen Mervi , Magnussen Costan G. , Mikkilä Vera , Siitonen Niina , Jokinen Eero , Laitinen Tomi , Würtz Peter , Gidding Samuel S. , Taittonen Leena , Seppälä Ilkka , Jula Antti , Kähönen Mika , Hutri-Kähönen Nina , Lehtimäki Terho , Viikari Jorma S.A. , Juonala Markus , Raitakari Olli T.
Published: June 2012

Background—

Hypertension is a major modifiable cardiovascular risk factor. The present longitudinal study aimed to examine the best combination of childhood physical and environmental factors to predict adult hypertension and furthermore whether newly identified genetic variants for blood pressure increase the prediction of adult hypertension.

Methods and Results—

The study cohort included 2625 individuals from the Cardiovascular Risk in Young Finns Study who were followed up for 21 to 27 years since baseline (1980; age, 3–18 years). In addition to dietary factors and biomarkers related to blood pressure, we examined whether a genetic risk score based on 29 newly identified single-nucleotide polymorphisms enhances the prediction of adult hypertension. Hypertension in adulthood was defined as systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥85 mm Hg or medication for the condition. Independent childhood risk factors for adult hypertension included the individual's own blood pressure (
P
<0.0001), parental hypertension (
P
<0.0001), childhood overweight/obesity (
P
=0.005), low parental occupational status (
P
=0.003), and high genetic risk score (
P
<0.0001). Risk assessment based on childhood overweight/obesity status, parental hypertension, and parental occupational status was superior in predicting hypertension compared with the approach using only data on childhood blood pressure levels (C statistics, 0.718 versus 0.733;
P
=0.0007). Inclusion of both parental hypertension history and data on novel genetic variants for hypertension further improved the C statistics (0.742;
P
=0.015).

Conclusions—

Prediction of adult hypertension was enhanced by taking into account known physical and environmental childhood risk factors, family history of hypertension, and novel genetic variants. A multifactorial approach may be useful in identifying children at high risk for adult hypertension.
Neural Interaction between Spatial Domain and Spatial Reference Frame in Parietal–Occipital Junction
Authors: Chen Qi , Weidner Ralph , Weiss Peter H. , Marshall John C. , Fink Gereon R.
Published: June 2012

On the basis of double dissociations in clinical symptoms of patients with unilateral visuospatial neglect, neuropsychological research distinguishes between different spatial domains (near vs. far) and different spatial reference frames (egocentric vs. allocentric). In this fMRI study, we investigated the neural interaction between spatial domains and spatial reference frames by constructing a virtual three-dimensional world and asking participants to perform either allocentric or egocentric judgments on an object located in either near or far space. Our results suggest that the parietal–occipital junction (POJ) not only shows a preference for near-space processing but is also involved in the neural interaction between spatial domains and spatial reference frames. Two dissociable streams of visual processing exist in the human brain: a ventral perception-related stream and a dorsal action-related stream. Consistent with the perception–action model, both far-space processing and allocentric judgments draw upon the ventral stream whereas both near-space processing and egocentric judgments draw upon the dorsal stream. POJ showed higher neural activity during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral) as compared with egocentric judgments (dorsal) in near space (dorsal) and allocentric judgments (ventral) in far space (ventral). Because representations in the dorsal and ventral streams need to interact during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral), our results imply that POJ is involved in the neural interaction between the two streams. Further evidence for the suggested role of POJ as a neural interface between the dorsal and ventral streams is provided by functional connectivity analysis.
Convergent Connectivity and Graded Specialization in the Rostral Human Temporal Lobe as Revealed by Diffusion-Weighted Imaging Probabilistic Tractography
Authors: Binney Richard J. , Parker Geoffrey J. M. , Lambon Ralph Matthew A.
Published: June 2012

In recent years, multiple independent neuroscience investigations have implicated critical roles for the rostral temporal lobe in auditory and visual perception, language, and semantic memory. Although arising in the context of different cognitive functions, most of these suggest that there is a gradual convergence of sensory information in the temporal lobe that culminates in modality- and perceptually invariant representations at the most rostral aspect. Currently, however, too little is known regarding connectivity within the human temporal lobe to be sure of exactly how and where convergence occurs; existing hypotheses are primarily derived on the basis of cross-species generalizations from invasive nonhuman primate studies, the validity of which is unclear, especially where language function is concerned. In this study, we map the connectivity of the human rostral temporal lobe in vivo for the first time using diffusion-weighted imaging probabilistic tractography. The results indicate that convergence of sensory information in the temporal lobe is in fact a graded process that occurs along both its longitudinal and lateral axes and culminates in the most rostral limits. We highlight the consistency of our results with those of prior functional neuroimaging, computational modeling, and patient studies. By going beyond simple fasciculus reconstruction, we systematically explored the connectivity of specific temporal lobe areas to frontal and parietal language regions. In contrast to the graded within-temporal lobe connectivity, this intertemporal connectivity was found to dissociate across caudal, mid, and rostral subregions. Furthermore, we identified a basal rostral temporal region with very limited connectivity to areas outside the temporal lobe, which aligns with recent evidence that this subregion underpins the extraction of modality- and context-invariant semantic representations.
Neuronal Correlates of Multiple Top–Down Signals during Covert Tracking of Moving Objects in Macaque Prefrontal Cortex
Authors: Matsushima Ayano , Tanaka Masaki
Published: June 2012

Resistance to distraction is a key component of executive functions and is strongly linked to the prefrontal cortex. Recent evidence suggests that neural mechanisms exist for selective suppression of task-irrelevant information. However, neuronal signals related to selective suppression have not yet been identified, whereas nonselective surround suppression, which results from attentional enhancement for relevant stimuli, has been well documented. This study examined single neuron activities in the lateral PFC when monkeys covertly tracked one of randomly moving objects. Although many neurons responded to the target, we also found a group of neurons that exhibited a selective response to the distractor that was visually identical to the target. Because most neurons were insensitive to an additional distractor that explicitly differed in color from the target, the brain seemed to monitor the distractor only when necessary to maintain internal object segregation. Our results suggest that the lateral PFC might provide at least two top–down signals during covert object tracking: one for enhancement of visual processing for the target and the other for selective suppression of visual processing for the distractor. These signals might work together to discriminate objects, thereby regulating both the sensitivity and specificity of target choice during covert object tracking.
Adolescents’ Stage-Environment Fit in Middle and High School
Authors: Booth Margaret Zoller , Gerard Jean M.
Published: June 2012

This mixed-methods longitudinal project investigates the association between student perceptions of their schools and themselves. Findings from the first two waves of data analysis with 894 middle and high school students in a midsized Great Lakes city reveal similarities and differences between the grade levels (7th-10th) and their perceptions of their schools. Although 7th-grade students enter middle school with the most positive feelings about their schools, they lose this feeling of euphoria by the end of their academic year. In contrast, the 10th-grade females are the most positive of all students, recognizing school characteristics which assist with their self-efficacy. Results from quantitative analyses indicate that student attitudes toward school and a sense of school connectedness are linked to both self-esteem and academic self-efficacy.
Stepfamily Education and Changes in Financial Practices
Authors: Higginbotham Brian J. , Tulane Sarah , Skogrand Linda
Published: June 2012

This study examined the financial management practices of 62 participants in Smart Steps stepfamily education courses 1 year following their course completion. Qualitative interviews revealed 29 participants changed their financial practices as a result of the course, 29 did not change, and 4 provided unclear responses. Common reasons for no change included having functional practices that predated the relationship education course or financial difficulties remaining, despite course participation. Common reasons for change included working together as a couple and implementing budget or saving practices. Latino participants were more likely to report change than were European Americans. Findings and implications highlight both the opportunities and challenges associated with teaching financial education as part of a relationship education program.
Sino‐Nasal Characteristics in Asthmatic Patients
Authors: Thorstensen Wenche Moe , Bugten Vegard , Sue‐Chu Malcolm , Fossland Nils Petter Wold , Romundstad Pål Richard , Steinsvåg Sverre Karmhus
Published: June 2012

Objective

The Unified Airways Hypothesis suggests an involvement of the upper airways in asthma. We aimed to evaluate the association between subjective sino‐nasal complaints, nasal air flow, and sino‐nasal quality of life (QOL) in patients with asthma compared with nonasthmatic subjects.

Study Design

Case‐control study.

Setting

A tertiary referral center.

Subjects and Methods

Symptoms, quality of life, and nasal airflow were assessed in 91 asthmatics and 95 nonasthmatic controls with Visual Analog Scale (VAS, 0‐100), Sino‐Nasal Outcome Test (SNOT‐20), and Peak Nasal Inspiratory Flow (PNIF), respectively. Asthma and allergy status were assessed by Asthma Control Questionnaire (ACQ) and skin prick test or specific IgE.

Results

Asthmatic patients (men/women, 37/54; mean age, 43.7 years; range, 19‐64 years) reported significantly more nasal obstruction (mean VAS, 37 mm; SD = 26, 95% CI, 32‐43 vs 9 mm, SD = 11, 95% CI, 7‐11, P <. 001) and lower sino‐nasal quality of life (mean SNOT‐20, 1.3; SD = 0.8, 95% CI, 1.1‐1.5 vs 0.4, SD = 0.5, 95% CI, 0.3‐0.5, P <. 001) than controls (men/women, 42/53; mean age, 43.8 years; range, 20‐65 years). PNIF was significantly lower in asthmatic patients than controls (mean PNIF, 84 l/min; SD = 24, 95% CI, 79‐89 vs 100 l/min SD = 24, 95% CI, 95‐105, P <. 001).

Conclusion

Both allergic and nonallergic asthma were associated with increased sino‐nasal symptoms, reduced sino‐nasal QOL, and reduced inspiratory nasal air flow compared to controls. This provides further evidence of the clinical importance of the upper airway in the diagnostic and therapeutic management of asthma patients beyond the scope of allergy.
Bilateral Bone‐Anchored Hearing Aids for Bilateral Permanent Conductive Hearing Loss
Authors: Janssen Renée M. , Hong Paul , Chadha Neil K.
Published: June 2012

Objective

To systematically review the outcomes of bilateral versus unilateral bone‐anchored hearing aids (BAHA) for individuals with bilateral permanent conductive hearing loss (CHL) with the goal of (1) deriving clinically oriented insights into the advantages and disadvantages of bilateral fitting and (2) identifying gaps in knowledge to stimulate future research.

Data Sources

Medline, EMBASE, and Cochrane databases were searched for studies of all languages published between 1977 and July 2011.

Review Methods

Studies were included if subjects of any age had permanent bilateral CHL and bilateral implanted BAHAs. Outcome measures of interest were any subjective or objective audiologic measures, quality of life indicators, or reports of adverse events.

Results

In all, 628 abstracts were generated from the literature searches; 11 studies met the criteria for data extraction and analysis. All 11 studies were observational. In most studies, comparisons between unilateral and bilateral BAHA were intra‐subject. Bilateral BAHA provided audiologic benefit compared to unilateral BAHA (improved thresholds for tones [2 studies], speech in quiet [5 studies] and in noise [3 studies], and improved localization/lateralization [3 studies]) and patients’ perceived subjective benefit from bilateral BAHA (3 studies). Disadvantages of bilateral BAHAs included listening in noise in some conditions (3 studies), presumed additional cost, and presumed increase in adverse event risk.

Conclusion

Bilateral BAHA provided additional objective and subjective benefit compared to unilateral BAHA; however, there was a limited number of studies available with good quality evidence. Aspects of bilateral BAHA that would benefit from further investigation are described, and recommendations for bilateral BAHA candidacy criteria are provided.
Effect of Continuous Positive Airway Pressure on C‐reactive Protein Levels in Sleep Apnea
Authors: Friedman Michael , Samuelson Christian G. , Hamilton Craig , Fisher Michelle , Kelley Kanwar , Joseph Ninos J. , Wang Pa‐Chun , Lin Hsin‐Ching
Published: June 2012

Objective

Evaluate the effects of continuous positive airway pressure (CPAP) on C‐reactive protein (CRP) levels, reported either as a primary or secondary end point among patients with obstructive sleep apnea‐hypopnea syndrome (OSAHS) based on a meta‐analysis of published studies.

Data Sources

English‐language searches of PubMed, Ovid, and the Cochrane databases were completed. Reference sections of identified studies were also examined for additional relevant articles to review.

Review Methods

Studies of adult patients with OSAHS who reported pre‐ and post‐CPAP treatment CRP were reviewed and analyzed. Two independent reviewers extracted data from 10 peer‐reviewed studies, which were combined using a random effects meta‐analysis model.

Results

The CPAP treatment was found to lead to a significant reduction in CRP levels (17.8%, P =. 002). This corresponds to an effect size of −0.485 (−0.731, −0.240). Sensitivity analysis was done to determine the impact of study design. Both case‐control studies and case‐series studies yielded a significant effect. Sensitivity analysis also yielded a significant effect for studies with average body mass index <30, studies where CPAP was employed over automatic positive airway pressure, and studies treating patients ≤3 months. Analysis of publication bias, however, revealed a likelihood of “missing” studies.

Conclusion

Although there is a significant lack of high‐quality studies addressing this question, this analysis suggests that treatment with CPAP leads to a statistically significant reduction in CRP levels. However, the mean pre‐ and posttreatment CRP levels observed are considered “high risk” for cardiovascular morbidity. The clinical significance of this finding as it relates to cardiovascular risk reduction and the relationship between CRP and OSAHS requires further study.