bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and Outcome of Chinese Patients with Both Antineutrophil Cytoplasmic Antibody and Antiglomerular Basement Membrane Antibodies
Authors: Zhao Juan , Yang Rui , Cui Zhao , Chen Min , Zhao Ming-Hui , Wang Hai-Yan
Published: September 2007

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (AASV) is a systemic autoimmune disease. A number of cases have been found to have antiglomerular basement membrane (GBM) antibody-positive serum. The purpose of the current article is to investigate the prevalence of anti-GBM antibodies in sera from a large cohort of Chinese patients with AASV and to characterize the clinical and pathological features of the ‘double positive’ patients. Methods: Sera from 652 patients with AASV were screened by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot analysis using purified human α(IV)NC1 as antigen. Antigen specificity of anti-GBM antibodies was determined by ELISA using recombinant human α3(IV)NC1 as solid phase ligand. Clinical and pathological data of patients with both ANCA and anti-GBM antibodies were analyzed retrospectively. Results: 61/652 (9.36%) sera from patients with AASV were serum anti-GBM antibody positive and all recognized recombinant human α3(IV)NC1. All the cases had renal involvement, 37/48 (77.1%) cases had pulmonary involvement, non-specific symptoms and other multisystem involvements were common. The renal survival was 14.6% (7/48) and patient survival was 37.5% (18/48) respectively at the end of 1 year. The following factors predicted poor prognosis: (1) serum creatinine >700 µmol/l (p = 0.034); (2) oliguria or anuria on diagnosis (p = 0.001); (3) high percentage (>85%) of glomeruli with crescents (p = 0.011); (4) high titer anti-GBM antibodies (p = 0.003), and (5) hemoptysis (p = 0.049). Conclusion: Patients with double antibodies were not rare in AASV. They had multisystem involvement but poor short-term prognosis.Anti-GBM antibodies should be detected on diagnosis of AASV, especially for old ages.
Caki-1 Cells Represent an in vitro Model System for Studying the Human Proximal Tubule Epithelium
Authors: Glube Natalie , Giessl Andreas , Wolfrum Uwe , Langguth Peter
Published: September 2007

Background/Aims: The human proximal tubule (PT) epithelium is distinguished from other nephron segments via several unique characteristics. Studies assessing PT epithelium increasingly employ cell lines, bypassing the complexity of primary cell cultures. However, few human model systems exist for studying PT cells in vitro. The current work involves an intensive characterization of Caki-1 cells, a commercially available human renal cell line. Methods: Caki-1 cells were validated as a representative model system for PT cell research via morphological, physiological and biochemical investigations including light and transmission electron microscopy, transepithelial electrical resistance (TER) measurements and the detection of PT markers. Results: Morphologically, these cells form a polarized monolayer with apical located microvilli and multiple mitochondria per cell. Low TER ranging from 2 to 28 Ω cm2 was determined for Caki-1 cells, characteristic of the ‘leaky’ PT epithelium in vivo. Expression of the PT markers: NHE3, GGT, DPP IV, APM and AP were present in Caki-1 cells. Two epithelial markers, E-cadherin and Na+/K+-ATPase, were additionally observed. Conclusion: The current work is a concise summary which confirms that Caki-1 cells represent well-differentiated polarized PT cells in vitro, regardless of its cancerous origin and multiple passaging. They prove to be a significant contribution to the field of PT research.
Safety of Imatinib in Chronic Myeloid Leukemia in Blastic Crisis Presenting as Cholestatic Jaundice
Authors: Ramamoorthy S. Kannan , Pandita Ramesh , Prakash Ajay , Ramaswamy N.V. , Al Bahar Soad
Published: September 2007

Acute leukemia presenting as cholestatic jaundice is rare. It can occur due to granulocytic sarcoma compressing the bile ducts in case of acute myeloid leukemia. Rarely, diffuse infiltration of the liver sinusoids by the leukemic blasts can present as cholestatic jaundice. We report a case of chronic myeloid leukemia in lymphoid blast cell crisis presenting with severe cholestatic jaundice due to diffuse infiltration of the liver sinusoids with lymphoblasts. This patient tolerated imatinib well and, coinciding with the hematological response, there was marked reduction in the cholestasis due to blast clearance from the hepatic sinusoids. He was subsequently treated with combination chemotherapy and achieved morphological and cytogenetic remission.
First Turkish Case of Bernard-Soulier Syndrome Associated with GPIX N45S
Authors: Dağıstan Necati , Kunishima Shinji
Published: September 2007

Bernard-Soulier syndrome (BSS) is a rare bleeding disorder characterized by giant platelets, thrombocytopenia, and a prolonged bleeding time. It is caused by homozygous defects in the glycoprotein (GP) Ib/IX/V complex, which is the receptor for the von Willebrand factor. We examined a Turkish patient with suspected BSS to identify a molecular basis. Flow cytometric analysis revealed that platelet GPIbα and GPIX expression was markedly reduced and DNA sequence analysis showed a homozygous N45S missense mutation in the GPIX gene. Haplotype analysis revealed that the family had the same disease haplotype associated with the GPIX N45S commonly found in Northern European BSS. This is the first non-Caucasian Turkish BSS case due to GPIX N45S and is likely the result of a recurrent mutational event.
Prevalence of Dental Fluorosis in German Schoolchildren in Areas with Different Preventive Programmes
Authors: Momeni A. , Neuhäuser A. , Renner N. , Heinzel-Gutenbrunner M. , Abou-Fidah J. , Rasch K. , Kröplin M. , Fejerskov O. , Pieper K.
Published: September 2007

In a retrospective study in two different regions of Germany, 1,041 fifteen-year-old pupils were examined for dental fluorosis. The adolescents had taken part in different caries prevention programmes. There were 746 subjects in the study group and 295 subjects in the control group. For each participant, specific aspects of early development, diet and fluoride exposure in group prevention programmes and at home were determined by means of questionnaires. The Thylstrup-Fejerskov index was used to classify the fluorosis scores on the buccal surfaces of teeth 11, 12, 13, 14, 15 and 16 after compressed air drying of the teeth. Binary logistic stepwise regression analyses were conducted to identify associations between fluorosis and potential influence factors. A distinction was made between early and late developing tooth parts. The significance level was set at α = 0.05. Fluorosis prevalence in the regions studied was 7.1 and 11.3%, respectively. The difference was not statistically significant (p = 0.052; chi square). Binary logistic stepwise regression analysis revealed that ‘early start of toothbrushing’ was a statistically significant predictor of dental fluorosis in the early-mineralizing enamel (OR = 1.99, p = 0.027). For the late-mineralizing enamel no single independent variable was identified as a significant predictor of dental fluorosis.
Salivary Glucosyltransferase B as a Possible Marker for Caries Activity
Authors: Vacca Smith A.M. , Scott-Anne K.M. , Whelehan M.T. , Berkowitz R.J. , Feng C. , Bowen W.H.
Published: September 2007

Bacteria-derived glucosyltransferases (Gtf) (EC 2.4.1.5), through synthesizing glucan polymers from sucrose and starch hydrolysates, play an essential role in the etiology and pathogenesis of caries. We attempted to correlate the levels of Gtf in whole saliva with the prevalence of carious lesions in young children. We examined saliva from children who were either free of overt carious lesions, or had severe early childhood caries (mean dmfs = 18.72 ± 9.0 SD), for Gtf by direct enzyme assay. The levels of GtfB, GtfC and GtfD from Streptococcus mutans in the saliva using monoclonal/specific antibodies in an enzyme-linked immunosorbent assay were determined. Multiple logistic regression analyses with model selection showed that GtfB levels correlated with dmfs values of the subjects (p = 0.006). There was no correlation between total Gtf activity as measured by direct enzyme assay and dmfs values. There was a strong correlation between mutans streptococci populations in saliva and caries activity. Collectively, these data show that GtfB levels in saliva correlate strongly with presence of clinical caries and with number of carious lesions in young children. It is also possible to measure different Gtfs, separately, in whole saliva. These observations may have important clinical implications, may lead to development of a chair side caries activity test and support the importance of GtfB in the pathogenesis of dental caries.
The Effect of Miswak Extract on Plaque pH
Authors: Sofrata A. , Lingström P. , Baljoon M. , Gustafsson A.
Published: September 2007

The aim of this study was to document changes in plaque pH when an acidic challenge was followed by rinsing with miswak extract (Salvadora persica), and to evaluate the effect of miswak rinse on parotid gland secretion rate. Plaque pH was measured in 3-day-old plaque using the microtouch electrode. Rinsing with miswak extract, compared with water rinsing, resulted in protracted elevation of plaque pH (>6.0). The difference in plaque pH between miswak extract and water rinse was statistically significant at 30 min (p < 0.001). Rinsing with miswak extract stimulated parotid gland secretion (p < 0.01). In conclusion, miswak extract raised the plaque pH, suggesting a potential role in caries prevention.
Caries-Preventive Effectiveness of a Fluoride Varnish: A Randomized Controlled Trial in Adolescents with Fixed Orthodontic Appliances
Authors: Stecksén-Blicks C. , Renfors G. , Oscarson N.D. , Bergstrand F. , Twetman S.
Published: September 2007

The aim was to evaluate the efficacy of topical fluoride varnish applications on white spot lesion (WSL) formation in adolescents during treatment with fixed orthodontic appliances. The study design was a double-blinded randomized placebo-controlled trial with two parallel arms. The subjects were 273 consecutive 12- to 15-year-old children referred for maxillary treatment with fixed orthodontic appliances. The patients were randomly assigned to a test or a control group with topical applications of either a fluoride varnish (Fluor Protector) or a placebo varnish every 6th week during the treatment period. The outcome measures at debonding were incidence and progression of WSL on the upper incisors, cuspids and premolars as scored from digital photographs by 2 independent examiners. The attrition rate was 5%. The mean number of varnish applications was 10 (range 4–20) in both groups. The incidence of WSL during the treatment with fixed appliances was 7.4% in the fluoride varnish compared to 25.3% placebo group (p < 0.001). The mean progression score was significantly lower in the fluoride varnish group than in the placebo group, 0.8 ± 2.0 vs. 2.6 ± 2.8 (p < 0.001). The absolute risk reduction was 18% and the number needed to treat was calculated to 5.5. The results from the present study strongly suggest that regular topical fluoride varnish applications during treatment with fixed appliances may reduce the development of WSL adjacent to the bracket base. Application of fluoride varnish should be advocated as a routine measure in orthodontic practice.
A New in vitro Model to Study the Relationship of Gap Size and Secondary Caries
Authors: Totiam P. , González-Cabezas C. , Fontana M.R. , Zero D.T.
Published: September 2007

Objectives: To investigate the relationship of gap size and secondary caries in a newly developed secondary caries microbial model that permits adjustment of the gap between the tooth and a restoration. Methods: Tooth-resin-matrix composite specimens were mounted on gap-model stages with a gap size of 50 or 500 µm in experiment 1, and 0, 25, 250, or 1,000 µm in experiment 2. They were attached to plastic Petri plates, gas-sterilized and then incubated in a microbial caries model (with Streptococcus mutans TH16 in 1% sucrose tryptic soy broth for 1 h, 4 times/day, and with a buffer solution for the rest of the day). After 8 days of incubation, tooth specimens were sectioned and stained overnight with a rhodamine B solution. Digital images taken under a confocal microscope were analyzed for lesion size at the outer surface lesion and wall lesion (WL). Results: Gap size was found to affect the development of dentin WL area in experiment 1 and enamel and dentin WL areas in experiment 2, with bigger lesions being observed in the wider gap group (p < 0.05). Conclusion: The findings of this study suggest that the size of the gap between tooth and restoration affects the development of secondary caries along the cavity wall.
Monovoxel 1H Magnetic Resonance Spectroscopy in the Progression of Gliomas
Authors: Alimenti Alessandro , Delavelle Jacqueline , Lazeyras François , Yilmaz Hasan , Dietrich Pierre-Yves , de Tribolet Nicolas , Lövblad Karl-Olof
Published: September 2007

Aim: Can monovoxel magnetic resonance spectroscopy (MRS) reliably follow tumour progression in low-grade glioma? Materials and Methods: 21 patients with low-grade glioma underwent at least 3 MRS. Results: For progression from a grade II to grade III tumour, a sensitivity of 57.1% and specificity of 60% were observed, with a positive predictive value (PPV) of 48.8% and a negative predictive value (NPV) of 54.5%. For progression under treatment, we obtained a sensitivity of 57.1% by N-acetylaspartate (NAA)/choline (Cho) and myoinositol/creatine (Cr) and a specificity of 100% by Cho/Cr and lipids, with a PPV of 80% and a NPV of 63.6%. Conclusion: We found that NAA/Cho is the best marker of tumour progression before therapy, with a sensitivity of 53.9%. For the therapeutic response, sensitivity was only 28.2%.
Cost-Minimization Analysis Comparing Topiramate with Standard Treatments in Migraine Prophylaxis
Authors: Ergun Hakan , Gulmez Sinem Ezgi , Tulunay F. Cankat
Published: September 2007

Migraine is a common disorder with a relatively high burden of disease from the perspective of both society and the individual patient. Optimizing the use of prophylactic treatment may decrease the frequency and severity of attacks thus reducing the burden of disease. In this regard, topiramate has been found to be as effective as propranolol in the prevention of migraine attacks. In the present study, a cost-minimization analysis was performed. Monthly preventive medication cost and price per migraine attack reduced were used as measures. In comparison with propranolol and flunarizine, topiramate was identified as being the most costly option for migraine prophylaxis with a monthly drug cost of USD 24.97–45.04 as compared with propranolol (USD 1.72–6.87) and flunarizine (USD 6.09–12.18). Current treatment options would appear to offer better value for money in achieving effective migraine prophylaxis unless additional benefits can be identified for topiramate in this patient group.
Contribution of Hematocrit to Early Mortality after Ischemic Stroke
Authors: Sacco Simona , Marini Carmine , Olivieri Luigi , Pistoia Francesca , Carolei Antonio
Published: September 2007

Background: Only a few non-recent studies assessed the importance of hematocrit (HCT) in patients with ischemic stroke. We evaluated how HCT might affect early mortality after stroke. Methods: We investigated all first-ever ischemic strokes included in the population-based L’Aquila registry. 3,481 patients according to HCT (%) values were included into four categories (≤40, 41–45, 46–50, and >50). Results: There were more men than women with HCT >50 (6.6 vs. 2.8%; p < 0.0001) and more women than men with HCT ≤40 (48.5 vs. 37.9%; p < 0.0001). Proportions of chronic atrial fibrillation (p = 0.0053) increased in women from the lower to the higher HCT categories. 7- and 28-day case-fatality rates were similar in men and women in the lower HCT categories but higher in women than in men in the higher categories. At the 28-day Kaplan-Meier analysis, men had similar survivals in the different categories while women with HCT >50 showed the worst survival (p < 0.0001). At the multivariate Cox regression analysis HCT 46–50 and >50 was an independent predictor of mortality in women within 28 days. Conclusion:High HCT might represent in women a previously underestimated independent predictor of mortality after ischemic stroke. Consideration of HCT in future stroke trials would be useful for ameliorating stroke care, especially in women.
Genistein Modifies Liver Fibrosis and Improves Liver Function by Inducing uPA Expression and Proteolytic Activity in CCl4-Treated Rats
Authors: Leija Salas Alfonso , Díaz Montezuma Tania , Garrido Fariña German , Reyes-Esparza Jorge , Rodríguez-Fragoso Lourdes
Published: September 2007

Aim: To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Methods: Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Results: Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Conclusion: Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease.
Silent Celiac Disease Is Frequent in the Siblings of Newly Diagnosed Celiac Patients
Authors: Bardella Maria Teresa , Elli Luca , Velio Pietro , Fredella Clara , Prampolini Luigia , Cesana Bruno
Published: September 2007

Background/Aims: Celiac disease is caused by environmental and genetic factors, and the relatives of celiac patients are at higher risk of developing celiac disease than the general population. This prospective study evaluates the prevalence of celiac disease in the asymptomatic siblings of celiac patients. Methods: Forty-eight siblings (22 males; mean age 13 years) of 39 celiac children (20 males; mean age 4 years), and 120 siblings (55 males; mean age 33 years) of 55 adult celiac patients (12 males; mean age 31 years) were serologically screened for celiac disease. Positive cases were considered for endoscopic duodenal biopsies. Results: Forty of the 168 asymptomatic siblings (23.8%) were affected by celiac disease. There were no differences between the index cases with and without affected siblings in terms of age at diagnosis, symptoms at onset, order of birth, associated disorders or other affected relatives. The male siblings of pediatric patients were affected in 40.9% of cases and female siblings in 26.9%; the corresponding figures for adults were 16.4 and 23.1%. Conclusions: Silent celiac disease is 24–48 times more frequent in the siblings of celiac patients than in the general population. No predictive factors for sibling involvement were found. Adult females seem to tolerate gluten less than adult males.
Inhibition of JAK/STAT Signaling Ameliorates Mice Experimental Nephrotic Syndrome
Authors: Li Rong , Yang Niansheng , Zhang Lili , Huang Yuefang , Zhang Rui , Wang Fang , Luo Mingqian , Liang Yingjie , Yu Xueqing
Published: September 2007

Background/Aims: This study investigated the role of JAK/STAT, an important pathway for cytokine signal transduction, in the progression of chronic glomerular diseases. Methods: BALB/c mice received a single intravenous injection of adriamycin (10 mg/kg) were sacrificed 2, 4 and 6 weeks later. In the second study, treatment with the selective JAK2 inhibitor AG490 (15 mg/kg, q.d., i.p.) or vehicle was started 5 days after adriamycin injection. Functional and pathologic markers, inflammatory infiltration, expression of pro-inflammatory cytokines and phosphorylation of JAK2/STATs were assessed. Results: JAK/STAT signaling was activated in adriamycin nephropathy. Phosphorylation of JAK2, STAT1 and STAT3 was significantly inhibited by AG490 (p <0.01). Compared to the vehicle-treated controls, AG490 treatment did not reduce proteinuria 2 weeks after induction of the disease, but resulted in significant decrease in proteinuria and serum creatinine at week 6 (p <0.05). Glomerulosclerosis, tubulointerstitial lesions and renal α-SMA expression were also significantly suppressed by AG490 treatment at week 6 (p < 0.01). In addition, AG490 inhibited the expression of MCP-1 mRNA, accompanied by reduced interstitial infiltration of macrophages and T cells (p <0.05). Conclusions: This study suggests that activation of JAK/STAT signaling is involved in the progression of glomerular diseases with proteinuric state.
Immunoglobulin-E-Mediated Reactivity to Self Antigens: A Controversial Issue
Authors: Zeller Sabine , Glaser Andreas G. , Vilhelmsson Monica , Rhyner Claudio , Crameri Reto
Published: September 2007

Immunoglobulin E (IgE) reactivity to self antigens is well established in vitro by ELISA, inhibition ELISA, Western blot analyses and T cell proliferation experiments. In vivo, IgE-binding self antigens are able to elicit strong type I reactions in sensitized individuals and, in the case of human manganese superoxide dismutase, to elicit eczematous reactions on healthy skin areas of patients suffering from atopic eczema. The reactions against self antigens sharing structural homology with environmental allergens can be plausibly explained by molecular mimicry between common B cell epitopes. For the second class of IgE-binding self antigens without sequence homology to known allergens, it is still unclear if the structures are able to induce a B cell switch to IgE production, or if the reactivity is due to sequence similarity shared with not yet detected environmental allergens. However, in all cases, cross-reactivity is never complete, indicating either a lower affinity of IgE antibodies to self allergens than to the homologous environmental allergens or the presence of additional B cell epitopes on the surface of the environmental allergens, or both. Increasing evidence shows that self allergens could play a decisive role in the exacerbation of long-lasting atopic diseases. However, the only observation supporting a clinical role of IgE-mediated autoreactivity is confined to the fact that IgE levels against self antigens correlate with disease severity.
Prevalence of IgE-Binding to Art v 1, Art v 4 and Amb a 1 in Mugwort-Allergic Patients
Authors: Oberhuber C. , Ma Y. , Wopfner N. , Gadermaier G. , Dedic A. , Niggemann B. , Maderegger B. , Gruber P. , Ferreira F. , Scheiner O. , Hoffmann-Sommergruber K.
Published: September 2007

Background: Mugwort (Artemisia vulgaris) represents an important source of weed pollen allergens. The objectives of the present study were (i) to analyze the IgE binding profiles in a group of mugwort-allergic patients, (ii) to identify individual marker allergens crucial for the diagnosis of mugwort allergy and (iii) to identify potential crossreactive allergens present in ragweed (Ambrosia artemisiifolia) pollen extract. Methods: Sera from 100 pediatric mugwort-allergic patients were analyzed for their IgE binding pattern to natural mugwort and ragweed pollen proteins, purified natural and recombinant Art v 1, recombinant Art v 4 and recombinant Amb a 1 using immunoblots and ELISA. Results: 91% of the patients’ sera tested displayed IgE binding to one or more mugwort pollen allergens in ELISA and 88% were positive in immunoblot. Purified natural Art v 1 was recognized by 79%, the recombinant protein by 39% of the patients tested and purified recombinant Art v 4 by 34% of the patients’ sera. 67% of the sera displayed crossreactive IgE to one or more ragweed pollen allergens. Recombinant Amb a 1 was noted in only 14% of the mugwort-allergic sera. Conclusions: Allergen-specific in vitro diagnosis was performed in 100 pediatric mugwort-allergic serum samples. Using two allergens (Art v 1 and Art v 4), 91% of the patients could be identified as mugwort pollen-sensitized patients by IgE in vitro tests. Crossreactivity to ragweed pollen allergens was demonstrated by in vitro experiments, suggesting a new important and potent allergen source expanding across Europe.
Inhibition of Basic Secretagogue-Induced Signaling in Mast Cells by Cell Permeable Gαi-Derived Peptides
Authors: Shefler Irit , Zavaro Orly , Raz Tamar , Baram Dana , Sagi-Eisenberg Ronit
Published: September 2007

Background: Basic secretagogues of connective tissue mast cells act as receptor mimetic agents that trigger mast cells by activating G proteins. This leads to simultaneous propagation of two signaling pathways: one that culminates in exocytosis, while the other involves protein tyrosine phosphorylation and leads to release of arachidonic acid metabolites. We have previously shown that introduction of a peptide that comprises the C-terminal end of Gαi3 into permeabilized mast cells inhibits basic secretagogue-induced exocytosis [Aridor et al., Science 1993;262:1569–1572]. We investigated whether cell-permeable peptides, composed of the C-terminus of Gαi3 fused with importation sequences, affect mast cell function. Methods: Following preincubation with the fused peptides, rat peritoneal mast cells were activated by compound 48/80 and analyzed for histamine and prostaglandin D2 release and protein tyrosine phosphorylations. Results: We demonstrate that out of three importation sequences tested only Gαi3 peptide fused with the Kaposi fibroblast growth factor importation sequence (ALL1) inhibited release of histamine. ALL1 as well as a cell-permeable peptide that corresponds to Gαi2 also blocked compound 48/80-stimulated protein tyrosine phosphorylation, though the latter did not block histamine release. ALL1 effect was G protein-specific, as it was incapable of blocking protein tyrosine phosphorylation stimulated by pervanadate. Conclusion: ALL1, a transducible Gαi3-corresponding peptide, blocks the two signaling pathways in mast cells: histamine release and protein tyrosine phosphorylation. Cell permeable peptides that block these two signaling cascades may constitute a novel approach for preventing the onset of the allergic reaction.
Regulation of Food Intake by Inflammatory Cytokines in the Brain
Authors: Buchanan Jessica B. , Johnson Rodney W.
Published: September 2007

A number of inflammatory cytokines are synthesized and released after activation of the immune system. In addition to other biological effects, these cytokines can potently inhibit food intake. Cytokine-mediated inhibition of food intake is of particular importance because excessive production of peripheral inflammatory cytokines is often associated with the cachexia-anorexia syndrome seen in some chronic diseases. The weight loss in cachexia is associated with an increase in morbidity and mortality. Understanding how cytokines regulate food intake may be crucial in enhancing quality of life and facilitating recovery in patients exhibiting cachexia. This review describes the main inflammatory cytokines that influence food intake and explores how peripheral cytokines communicate with hypothalamic nuclei to influence feeding.
The Fontan Procedure
Authors: d’Udekem Yves , Iyengar Ajay J. , Cochrane Andrew D. , Grigg Leeanne E. , Ramsay James M. , Wheaton Gavin R. , Penny Dan J. , Brizard Christian P.
Published: September 2007

Background—

To determine whether patients undergoing the lateral tunnel and extracardiac conduit modifications of the Fontan procedure have better outcomes than patients undergoing a classical atriopulmonary connection.

Methods and Results—

Between 1980 and 2000, 305 consecutive patients underwent a Fontan procedure at our institution. There were 10 hospital deaths (mortality: 3%) with no death after 1990. Independent risk factors for mortality were preoperative elevated pulmonary artery pressures (
P
=0.002) and common atrioventricular valve (
P
=0.04). Fontan was taken down during hospital stay in 7 patients. A mean of 12±6 years of follow-up was obtained in the 257 nonforeign Fontan survivors. Completeness of concurrent follow-up was 96%. Twenty-year survival was 84% (95% CI: 79 to 89%). Recent techniques improved late survival. The 15-year survival after atriopulmonary connection was 81% (95% CI: 73% to 87%) versus 94% (95% CI: 79% to 98%) for lateral tunnel (
P
=0.004). Nine pts required heart transplantation (8 atriopulmonary connection, 1 lateral tunnel). Undergoing a Fontan modification independently predicted decreased occurrence of arrhythmia, and 15-year freedom from SVT was 61% (95% CI: 51% to 70%) for atriopulmonary connection versus 87% (95% CI: 76% to 93%) for lateral tunnel (
P
=0.02). Freedom from Fontan failure (death, take-down, transplantation, or NYHA class III-IV) was 70% (95% CI: 58% to 79%) at 20 years. After extra-cardiac conduits, no death, SVT, or failure was observed.

Conclusions—

The Fontan procedure remains a palliation, but outcomes of patients have improved. Better patient selection minimizes hospital mortality. Patients with lateral tunnel and extracardiac conduit modifications experience less arrhythmia and are likely to have failure of their Fontan circulation postponed.
Transapical Minimally Invasive Aortic Valve Implantation
Authors: Walther Thomas , Simon Paul , Dewey Todd , Wimmer-Greinecker Gerhard , Falk Volkmar , Kasimir Marie T. , Doss Mirko , Borger Michael A. , Schuler Gerhard , Glogar Dietmar , Fehske Wolfgang , Wolner Ernst , Mohr Friedrich W. , Mack Michael
Published: September 2007

Background—

To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis.

Methods and Results—

TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81±6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27±14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26-mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7±5.9% at a follow-up interval of 110±77 days (range 1 to 255 days).

Conclusions—

TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied.
Hemodynamic and Exercise Performance With Pulsatile and Continuous-Flow Left Ventricular Assist Devices
Authors: Haft Jonathan , Armstrong William , Dyke David B. , Aaronson Keith D. , Koelling Todd M. , Farrar David J. , Pagani Francis D.
Published: September 2007

Background—

Continuous-flow rotary pumps with axial design are increasingly used for left ventricular assist support. The efficacy of this design compared with pulsatile, volume displacement pumps, with respect to characteristics of left ventricular unloading, and exercise performance remains largely unstudied.

Methods and Results—

Thirty-four patients undergoing implantation with a pulsatile, volume displacement pump operating in a full-to-empty cycle (HeartMate XVE; Thoratec Inc, Pleasanton, Calif; n=16) or continuous-flow rotary pump with an axial design operating at a fixed rotor speed (HeartMate II; Thoratec Inc; n=18) were evaluated with right heart catheterization and echocardiography preoperatively and at 3 months postoperatively and cardiopulmonary exercise testing 3 months postoperatively. Support with either the XVE or II resulted in significant (
P
<0.05) increases in cardiac output and reduction in mean pulmonary artery and pulmonary wedge pressures. Exercise capacity at 3 months was similar between groups (% predicted peak V̇
o
2
−XVE: 46.8±10.2 versus II: 49.1±13.6). Echocardiography at 3 months demonstrated a significantly (
P
<0.05) greater reduction in left ventricular end-diastolic volume (−49±16% versus −35±20%), left ventricular end-systolic volume (−59±20 versus −37±21%), and percent mitral valve regurgitant volume (−99±2% versus −52±56%) for the XVE compared with II, respectively.

Conclusions—

The HeartMate XVE or II provided equivalent degrees of hemodynamic support and exercise capacity. The XVE was associated with greater left ventricular volume unloading. Characteristics of left ventricular pressure and volume unloading between these pump designs and mode of operation do not influence early exercise performance.
Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass
Authors: Pretorius Mias , Donahue Brian S. , Yu Chang , Greelish James P. , Roden Dan M. , Brown Nancy J.
Published: September 2007

Background—

Postoperative atrial fibrillation (AF), leading to significant morbidity and prolongation of hospital stay, complicates 20% to 40% of surgical procedures requiring cardiopulmonary bypass (CPB). This study tests the hypothesis that biomarkers predict the development of postoperative AF.

Methods and Results—

We enrolled 253 adult patients undergoing elective cardiac surgery requiring CPB and who were in sinus rhythm at the time of surgery. Blood samples were obtained for measurement of 21 biomarkers immediately after separation from CPB and administration of protamine. Patients who developed postoperative AF (67 subjects, 26.5%) were significantly older (
P
<0.001), more likely to have a remote history of AF (
P
<0.001), and tended to be more likely to have had valve surgery (
P
=0.082). Plasminogen activator inhibitor-1 (
P
=0.014), interleukin (IL)-6 (
P
=0.019), and N-terminal prohormone brain natriuretic peptide (
P
=0.028) concentrations were significantly higher in the blood of patients who developed postoperative AF. Logistic regression identified age (
P
<0.001), remote history of AF (
P
=0.001), and postoperative PAI-1 (
P
=0.036) as independent predictors of postoperative AF. When preoperative PAI-1 antigen concentrations were included in the model age (
P
<0.001), remote history of AF (
P
<0.001) and preoperative PAI-1 (
P
=0.015) were identified as independent predictors of postoperative AF. The Chi-squared Automatic Interaction Detection (CHAID) model indicated that age was the primary determinant for the development of postoperative AF (17% in age ≤67.3 years versus 49% in age >67.3 years). Within younger patients (age ≤67.3 years) without remote history of AF, postoperative PAI-1 antigen concentration next determined risk of AF (13% if PAI-1≤28.5 ng/mL versus 46% if PAI-1>28.5 ng/mL).

Conclusion—

An elevated preoperative or postoperative PAI-1 antigen concentration is an independent predictor for development of AF after CPB. Studies are needed to determine whether drugs that reduce PAI-1 concentrations can also reduce the risk of postoperative AF.
To Drink or Not to Drink? That Is the Question
Authors: Kloner Robert A. , Rezkalla Shereif H.
Published: September 2007

Numerous studies have used a J-shaped or U-shaped curve to describe the relationship between alcohol use and total mortality. The nadir of the curves based on recent meta-analysis suggested optimal benefit at approximately half a drink per day. Fewer than 4 drinks per day in men and fewer than 2 per day in women appeared to confer benefit. Reductions in cardiovascular death and nonfatal myocardial infarction were also associated with light to moderate alcohol intake. Although some studies suggested that wine had an advantage over other types of alcoholic beverages, other studies suggested that the type of drink was not important. Heavy drinking was associated with an increase in mortality, hypertension, alcoholic cardiomyopathy, cancer, and cerebrovascular events, including cerebrovascular hemorrhage. Paradoxically, light-to-moderate alcohol use actually reduced the development of heart failure and did not appear to exacerbate it in most patients who had underlying heart failure. Numerous mechanisms have been proposed to explain the benefit that light-to-moderate alcohol intake has on the heart, including an increase of high-density lipoprotein cholesterol, reduction in plasma viscosity and fibrinogen concentration, increase in fibrinolysis, decrease in platelet aggregation, improvement in endothelial function, reduction of inflammation, and promotion of antioxidant effects. Controversy exists on whether alcohol has a direct cardioprotective effect on ischemic myocardium. Studies from our laboratory do not support the concept that alcohol has a direct cardioprotective effect on ischemic/reperfused myocardium. Perhaps the time has come for a prospectively randomized trial to determine whether 1 drink per day (or perhaps 1 drink every other day) reduces mortality and major cardiovascular events.
Bone Marrow–Derived Mesenchymal Cell Mobilization by Granulocyte-Colony Stimulating Factor After Acute Myocardial Infarction
Authors: Ripa Rasmus Sejersten , Haack-Sørensen Mandana , Wang Yongzhong , Jørgensen Erik , Mortensen Steen , Bindslev Lene , Friis Tina , Kastrup Jens
Published: September 2007

Background—

Granulocyte-colony stimulating factor (G-CSF) after myocardial infarction does not affect systolic function when compared with placebo. In contrast, intracoronary infusion of bone marrow cells appears to improve ejection fraction. We aimed to evaluate the G-CSF mobilization of subsets of stem cells.

Methods and Results—

We included 78 patients (62 men; 56±8 years) with ST-elevation myocardial infarction treated with primary percutaneous intervention <12 hours after symptom onset. Patients were randomized to double-blind G-CSF (10 μg/kg/d) or placebo. Over 7 days, the myocardium was exposed to 25×10
9
G-CSF mobilized CD34
+
cells, compared with 3×10
9
cells in placebo patients (
P
<0.001); and to 4.9×10
11
mesenchymal stem cells, compared with 2.0×10
11
in the placebo group (
P
<0.001). The fraction of CD34
+
cells/leukocyte increased during G-CSF treatment (from 0.3±0.2 to 1.1±0.9 ×10
−3
,
P
<0.001 when compared with placebo), whereas the fraction of putative mesenchymal stem cells/leukocyte decreased (from 22±17 to 14±11 ×10
−3
,
P
=0.01 when compared with placebo). An inverse association between number of circulating mesenchymal stem cells and change in ejection fraction was found (regression coefficient −6.8,
P
=0.004), however none of the mesenchymal cell subtypes analyzed, were independent predictors of systolic recovery.

Conclusions—

The dissociated pattern for circulating CD34
+
and mesenchymal stem cells could be attributable to reduced mesenchymal stem cell mobilization from the bone marrow by G-CSF, or increased homing of mesenchymal stem cells to the infarcted myocardium. The inverse association between circulating mesenchymal stem cells and systolic recovery may be of clinical importance and should be explored further.
Autograft Regurgitation and Aortic Root Dimensions After the Ross Procedure
Authors: Hanke Thorsten , Stierle Ulrich , Boehm Juergen O. , Botha Cornelius A. , Matthias Bechtel J.F. , Erasmi Armin , Misfeld Martin , Hemmer Wolfgang , Rein Joachim G. , Robinson Derek R. , Lange Rüdiger , Hörer Jürgen , Moritz Anton , Özaslan Feyzan , Wahlers Thorsten , Franke Ulrich F.W. , Hetzer Roland , Hübler Michael , Ziemer Gerhard , Graf Bernhard , Ross Donald N. , Sievers Hans H.
Published: September 2007

Background—

Autograft regurgitation and root dilatation after the Ross procedure is of major concern. We reviewed data from the German Ross Registry to document the development of autograft regurgitation and root dilatation with time and also to compare 2 different techniques of autograft implantation.

Methods and Results—

Between 1990 and 2006 1014 patients (786 men, 228 women; mean age 41.2±15.3 years) underwent the Ross procedure using 2 different implantation techniques (subcoronary, n =521; root replacement, n =493). Clinical and serial echocardiographic follow up was performed preoperatively and thereafter annually (mean follow up 4.41±3.11 years, median 3.93 years, range 0 to 16.04 years; 5012 patient-years). For statistical analysis of serial echocardiograms, a hierarchical multilevel modeling technique was applied. Eight early and 28 late deaths were observed. Pulmonary autograft reoperations were required in 35 patients. Initial autograft regurgitation grade was 0.49 (root replacement 0.73, subcoronary 0.38) with an annual increase of grade 0.034 (root replacement 0.0259, subcoronary 0.0231). Annulus and sinus dimensions did not exhibit an essential increase over time in both techniques, whereas sinotubular junction diameter increased essentially by 0.5 mm per year in patients with root replacement. Patients with the subcoronary implantation technique showed nearly unchanged dimensions. Bicuspid aortic valve morphology did not have any consistent impact on root dimensions with time irrespective of the performed surgical technique.

Conclusions—

The present Ross series from the German Ross Registry showed favorable clinical and hemodynamic results. Development of autograft regurgitation for both techniques was small and the annual progression thereof is currently not substantial. Use of the subcoronary technique and aortic root interventions with stabilizing measures in root replacement patients seem to prevent autograft regurgitation and dilatation of the aortic root within the timeframe studied.
Twenty Years Experience With the Gastroepiploic Artery Graft for CABG
Authors: Suma Hisayoshi , Tanabe Hiroaki , Takahashi Akihito , Horii Taiko , Isomura Tadashi , Hirose Hitoshi , Amano Atsushi
Published: September 2007

Background—

To improve the longterm outcome after CABG, several strategies have been used using arterial conduits. Our 20 years experience with the right gastroepiploic artery (GEA) graft was evaluated.

Methods and Results—

In 1352 patients having CABG with the GEA graft, (1092 men, mean 63 years, 99% multivessel disease, and mean EF 0.51), internal thoracic artery, saphenous vein, and radial artery grafts were concomitantly used in 1312 (97%), 783 (58%), and 128 (8%) patients, respectively. The mean number of distal anastomoses was 3.1, and 2.4 coronary arteries were bypassed with arterial grafts. The sites for GEA grafting were 70 anterior descending, 268 circumflex, and 1089 right coronary arteries. The operative mortality was 1.26%. In 1118 follow-up patients (82.6%), 5, 10, and 15 years survival rates were 91.7%, 81.4%, and 71.3%, and the cardiac death-free survival rates were 95.8%, 91.7%, and 88.6%, respectively. The cumulative patency rate of the GEA graft was 97.1% at 1 month, 92.3% at 1 year, 85.5% at 5 years, and 66.5% at 10 years, respectively. In 172 skeletonized GEA grafts with 233 distal anastomoses, the patency rate at immediate, 1, and 4 years after surgery was 97.6%, 92.9%, and 86.4%, respectively. In 124 patients with late (5 to 17 years) restudy, patency rate was 96% (114/119) in the left internal thoracic artery, 87% (108/124) in GEA, and 68% (67/98) in saphenous vein grafts. New stenosis was uncommon in GEA.

Conclusion—

The GEA graft is a safe and effective arterial conduit for CABG.
Off-Pump Techniques Disproportionately Benefit Women and Narrow the Gender Disparity in Outcomes After Coronary Artery Bypass Surgery
Authors: Puskas John D. , Kilgo Patrick D. , Kutner Michael , Pusca Sorin V. , Lattouf Omar , Guyton Robert A.
Published: September 2007

Background—

Women experience greater morbidity and mortality than men after conventional coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB). The objective of this study was to determine whether off-pump CABG (OPCAB) alters this gender-based disparity.

Methods and Results—

Retrospective review of risk factors and clinical outcomes for 11 413 consecutive patients having isolated CABG between January 1, 1997, and May 31, 2005, at a US academic center. Interventions were OPCAB or CABG/CPB, performed at the discretion of 14 faculty surgeons. Main outcome measures included in-hospital death, stroke, myocardial infarction or combined major adverse cardiac events (MACE=death or stroke or myocardial infarction). Odds ratios of adverse events, adjusted for 31 risk factors, were compared between women and men who had OPCAB versus CABG/CPB. Covariates included Propensity Score, Society of Thoracic Surgeons’ Predicted Risk, surgeon and body habitus. Female patients (n=3248) and those treated with OPCAB (n=4492) were older, had more comorbidities and higher predicted risk than male patients (n=8165) and those treated with conventional CABG/CPB (n=6921), respectively. Women treated with CABG/CPB had a risk-adjusted odds ratio of 1.60 for death (
P
=0.01), 1.71 for stroke (
P
=0.007), 2.26 for myocardial infarction (
P
=0.008) and 1.71 for MACE (
P
<0.001) compared with men who had CABG/CPB. In contrast, women treated with OPCAB had outcomes statistically similar to men who had either OPCAB or CABG/CPB. Among women, OPCAB was associated with a significant reduction in death (OR 0.39,
P
=0.001), stroke (OR 0.43,
P
=0.002) and MACE (OR 0.43,
P
<0.001).

Conclusions—

OPCAB is associated with fewer major adverse cardiac events and benefits women disproportionately, thereby narrowing the gender disparity in clinical outcomes after CABG.