bluuebunny/crossref_metadata_2025 huggingface dataset:
A Curcumin‐Based 1‐Week Triple Therapy for Eradication of Helicobacter pylori Infection: Something to Learn From Failure?
Authors: Di Mario Francesco , Cavallaro Lucas G. , Nouvenne Antonio , Stefani Nicoletta , Cavestro Giulia M. , Iori Veronica , Maino Marta , Comparato Giuseppe , Fanigliulo Libera , Morana Ester , Pilotto Alberto , Martelli Laura , Martelli Mario , Leandro Gioacchino , Franzè Angelo
Published: May 2007

Background:  Curcumin is the principal element of turmeric powder extracted from the root of Curcuma longa. Studies on curcumin have demonstrated some anti‐Helicobacter pylori activity as well as immunomodulating properties. N‐acetylcysteine and lactoferrin with their respective mucolytic and antibacterial activities might also be effective in H. pylori eradication therapy.

Aim:  To determine if a 7‐day non‐antibiotic therapy comprised of curcumin, lactoferrin, N‐acetylcysteine, and pantoprazole was effective for eradication of H. pylori infection and reduction of gastric inflammation, assessed by serum pepsinogens and relief of symptoms.

Subjects and Methods:  Twenty‐five consecutive H. pylori‐positive patients (12 males, mean age 50 ± 12 years, range 31–76) with functional dyspepsia were enrolled. Patients were administered for 7 days curcumin 30 mg b.i.d., bovine lactoferrin 100 mg b.i.d., N‐acetylcysteine 600 mg b.i.d., and pantoprazole 20 mg b.i.d. H. pylori status and upper gastrointestinal symptoms were assessed by 13C‐urea breath test and a scale of upper gastrointestinal symptoms intensity (absent, mild, moderate, and severe), as well as a blood test for serum pepsinogens (sPGI, sPGII), gastrin‐17 (G‐17), and anti‐H. pylori IgG (IgG‐Hp) at baseline (T0) and after 2 months (T1).

Results:  Three of 25 patients (12%) were cured of H. pylori infection. A significant decrease in the overall severity of symptoms (T0: 6, interquartile range [IQR]: 4.5–8; T1: 2, IQR: 2–3; p ≤ .001), and sPGII (T0: 16 µg/L, IQR: 13–22; T1: 10 µg/L, IQR: 8–16; p ≤ .001) and sPGI (T0: 82 µg/L, IQR: 67–97; T1: 74 µg/L, IQR: 62–94; p = .02) levels were observed after 2 months of the treatment. IgG and G‐17 values did not significantly decrease after 2 months.

Conclusions:  This novel therapy was not effective for H. pylori eradication. However, despite the bacterium persistence, significant improvement of dyspeptic symptoms and reduction of serologic signs of gastric inflammation were observed after 2 months at the end of the 7‐day treatment schedule.
HorB (HP0127) is a Gastric Epithelial Cell Adhesin
Authors: Snelling William J. , Moran Anthony P. , Ryan Kieran A. , Scully Paul , McGourty Kieran , Cooney Jakki C. , Annuk Heidi , O'Toole Paul W.
Published: May 2007

Background:  The Helicobacter pylori protein HorB (encoded by HP0127) is a member of a paralogous family that includes the adhesins BabA, AlpA, AlpB, and HopZ, which contribute to adhesion to gastric epithelial cells. Of the verified H. pylori porins, the HorB sequence is most similar to that of HopE, but the function of HorB is unknown. The aim of our study was to investigate the role of HorB in H. pylori gastric epithelial cell adhesion.

Materials and methods:  We disrupted the horB gene in H. pylori and measured the adhesion to gastric epithelial cells (AGS cells). We then assessed the effect that HorB disruption had on lipopolysaccharide (LPS) O‐chain production and Lewis x and Lewis y antigen expression. A HorB mutant in the mouse‐adapted strain H. pylori SS1 was created by marker exchange and mouse stomach colonization was quantified. Using reverse transcription polymerase chain reaction, human gastric biopsy material from H. pylori‐infected patients was then examined for expression of the horB gene.

Results:  Disruption of the horB gene reduced H. pylori adhesion by more than twofold. Adhesion in the horB knockout strain was restored to wild‐type levels by re‐introduction of HorB into the chromosome. Disruption of HorB reduced production of LPS O‐chains and lowered the level of expression of Lewis x and Lewis y antigens. Insertional mutagenesis of the horB gene in H. pylori SS1 reduced mouse stomach colonization threefold. Finally, expression of the horB gene was detected in human gastric biopsy material from H. pylori‐infected patients.

Conclusions:  From these data we conclude that HorB has a role in H. pylori adhesion during infection.
Proof of an Association betweenHelicobacter pyloriand Idiopathic Thrombocytopenic Purpura in Latin America
Authors: Campuzano‐Maya Germán
Published: May 2007

Background: Association betweenHelicobacter pyloriand idiopathic thrombocytopenic purpura (ITP) has been found in Japan and in some European countries. It has also been shown that eradication ofH. pylorican increase platelet counts in patients with ITP. The aims of this study were to determine the prevalence ofH. pyloriinfection in patients with ITP in Colombia, and the effect of bacterial eradication on their platelet counts.

Materials and methods: Between December 1998 and April 2006, a total of 32 patients diagnosed with ITP were included in the study. Controls were age and sex matched.

Results: H. pyloriinfection in patients with ITP was significantly higher (p = .00006) than in control individuals (90.6% and 43.8%, respectively), as determined by13C‐urea breath test. A significant association betweenH. pyloriinfection and ITP was found (p < .0003), with an odds ratio (OR) of 13.15 (95%CI: 3.24–53.29). Multivariate analysis for the association betweenH. pyloriand ITP showed an OR of 20.44 (95%CI: 3.88–107.49) for women and 19.28 (95%CI: 2.03–183.42) for individuals over 50 years. All 29H. pylori‐positive patients with ITP received eradication treatment. After a median follow up of 12.2 months, 80.8% had a recovery in platelet counts.

Conclusions: According to these results and others from different countries whereH. pyloriinfection rates are high, patients with ITP should be initially tested forH. pyloristatus, and if present, infection should be eradicated before initiating a drastic conventional ITP treatment. An algorithm for the study and management of patients with ITP in the post‐Helicobacterera is presented.
Eclogite and carpholite‐bearing metasedimentary rocks in the North Qilian suture zone, NW China: implications for Early Palaeozoic cold oceanic subduction and water transport into mantle
Authors: SONG S. G. , ZHANG L. F. , NIU Y. , WEI C. J. , LIOU J. G. , SHU G. M.
Published: May 2007

Low‐temperature eclogite and eclogite facies metapelite together with serpentinite and marble occur as blocks within foliated blueschist that was originated from greywacke matrix; they formed a high‐pressure low‐temperature (HPLT) subduction complex (mélange) in the North Qilian oceanic‐type suture zone, NW China. Phengite–eclogite (type I) and epidote–eclogite (type II) were recognized on the basis of mineral assemblage. Relic lawsonite and lawsonite pseudomorphs occur as inclusions in garnet from both types of eclogite. Garnet–omphacite–phengite geothermobarometry yields metamorphic conditions of 460–510 °C and 2.20–2.60 GPa for weakly deformed eclogite, and 475–500 °C and 1.75–1.95 GPa for strongly foliated eclogite. Eclogite facies metasediments include garnet–omphacite–phengite–glaucophane schist and various chloritoid‐bearing schists. Mg‐carpholite was identified in some high‐Mg chloritoid schists.P–Testimates yield 2.60–2.15 GPa and 495–540 °C for Grt–Omp–Phn–Gln schist, and 2.45–2.50 GPa and 525–530 °C for the Mg‐carpholite schist. Mineral assemblages andP–Testimates, together with isotopic ages, suggest that the oceanic lithosphere as well as pelagic to semi‐pelagic sediments have been subducted to the mantle depths (≥75 km) before 460 Ma. Blueschist facies retrogression occurred atc.454–446 Ma and led to eclogite deformation and dehydration of lawsonite during exhumation. The peakP–Tconditions for eclogite and metapelite in the North Qilian suture zone demonstrate the existence of cold subduction‐zone gradients (6–7 °C km−1), and this cold subduction brought a large amount of H2O to the deep mantle in the Early Palaeozoic times.
BNP Consensus Panel 2004: A Clinical Approach for the Diagnostic, Prognostic, Screening, Treatment Monitoring, and Therapeutic Roles of Natriuretic Peptides in Cardiovascular Diseases
Authors: Silver Marc A. , Maisel Alan , Yancy Clyde W. , McCullough Peter A. , Burnett John C. , Francis Gary S. , Mehra Mandeep R. , William Franklin Peacock IV, MD  , Fonarow Gregg , Gibler W. Brian , Morrow David A. , Hollander Judd
Published: May 2007

Among the most exciting developments in the field of heart failure in recent times has been the rediscovery of the natriuretic peptide system and its pleuripotent effects on cardiac structure and function. This is particularly true of its natriuretic and hemodynamic effects. There has been an explosion of the knowledge base seeking to understand the wide range of homeostatic, regulatory, and counter‐regulatory functions in which the natriuretic peptide system participates. Additional interest has been stimulated by advances in technology such as point‐of‐care and core laboratory BNP assays and the use of the recombinant B‐type natriuretic peptide nesiritide as a treatment option. Despite this recent interest, the available literature lacks a comprehensive expert review of the current science and roles of natriuretic peptides for diagnostic, prognostic, screening, treatment monitoring, and therapeutic purposes. More importantly, a summary updating and guiding the clinician on most of these advances was lacking. An expert Consensus Panel with basic, methodological, and clinical expertise was convened to summarize current knowledge in these areas and the findings and consensus statements are contained herein.
Unusual Presentation of Cardiac Sarcoidosis
Authors: Tandri Harikrishna , Bomma Chandra , Calkins Hugh
Published: May 2007

A 46‐year‐old white woman presented to the emergency department with hemodynamically stable sustained ventricular tachycardia (VT). She was chemically cardioverted with lidocaine. Her electrocardiogram, showing sinus rhythm, was unremarkable, and serial cardiac enzyme tests excluded myocardial infarction. A signal‐averaged electrocardiogram was abnormal, with a filtered QRS duration of 187 milliseconds. Echocardiography showed normal left and right ventricular systolic function but revealed diastolic dysfunction of the left ventricle. Electrophysiologic testing revealed easily inducible sustained VT of 4 distinct morphologies. A diagnosis of possible arrhythmogenic right ventricular dysplasia was made based on the signal‐averaged electrocardiographic and electrophysiologic findings. Cardiac magnetic resonance imaging showed no evidence of arrhythmogenic right ventricular dysplasia, however. An endomyocardial biopsy revealed noncaseating granulomas consistent with sarcoidosis. This case illustrates the importance of complete testing, including invasive studies such as endomyocardial biopsy, in patients presenting with life‐threatening ventricular arrhythmias to establish a correct diagnosis.
The Physical Examination in Heart Failure—Part II
Authors: Leier Carl V. , Chatterjee Kanu
Published: May 2007

The major components of the physical examination of patients with heart failure are presented to allow practical application by physicians and nurses working in this arena. Part II contains the key elements of the chest, precordial‐cardiac, hepatic, and peripheral examination in this specific clinical setting. Supplemental maneuvers are provided. Finally, the overall role and merits of the physical examination in managing the heart failure patient are discussed.
PARASITIC SPECIES OF THE GENUS BLASTODINIUM (BLASTODINIPHYCEAE) ARE PERIDINIOID DINOFLAGELLATES1
Authors: Skovgaard Alf , Massana Ramon , Saiz Enric
Published: May 2007

The taxonomic position of Blastodinium navicula Chatton and B. contortum Chatton, parasites of marine copepods, was investigated on the basis of morphological observations and molecular data. The life cycle of Blastodinium includes a parasitic stage, a trophont, and free‐swimming dinospores. The individual cells in the trophont, as well as the dinospores that they produced, were thecate. Dinospores of B. contortum and B. navicula had peridinioid plate tabulation formula, demonstrating an affiliation to the order Peridiniales Heackel (subdivision Dinokaryota Fensome et al.). This systematic position is in contrast to current classifications, in which the order Blastodiniales Chatton is thought to represent an early evolutionary branch of the dinokaryote lineage. Small‐subunit rRNA gene sequences were generated from six Blastodinium individuals isolated from three different host species. In phylogenetic analyses based on SSU rRNA genes, Blastodinium spp. branched with the typical dinoflagellates. Even though overall statistical support was low, the analyses suggested that Blastodinium spp. are late‐branching, dinokaryote dinoflagellates. Species currently included in Blastodiniales are all parasites, but they are morphologically and functionally diverse. Emerging molecular data also reveal high genetic diversity, and therefore, the taxonomy of the group requires reevaluation.
SEDIMENTARY IMPRINT OF MICROCYSTIS AERUGINOSA (CYANOBACTERIA) BLOOMS IN GRANGENT RESERVOIR (LOIRE, FRANCE)1
Authors: Latour Delphine , Salençon Marie‐José , Reyss Jean‐Louis , Giraudet Hervé
Published: May 2007

Analysis of a sediment core taken from the Grangent reservoir in 2004 showed the presence of high concentrations of Microcystis aeruginosa Kütz. colonies at the sediment surface (250 colonies · mL sediment−1) and also at depths of 25–35 cm (2300 colonies·mL sediment−1) and 70 cm (600 colonies · mL sediment−1). Measurements of radioactive isotopes (7Be, 137Cs, and 241Am) along with photographic analysis of the core were used to date the deep layers: the layer located at −30 cm dates from summer 2003, and that located at −70 cm from 1990 to 1991. The physiological and morphological conditions of those benthic colonies were compared with those of planktonic colonies using several techniques (environmental scanning electron microscopy [ESEM], TEM, DNA markers, cellular esterases, and toxins). The ESEM observations showed that, as these colonies age, peripheral cells disappear, with no cells remaining in the mucilage of the deepest colonies (70 cm), an indication of the survival thresholds of these organisms. In the benthic phase, the physiological conditions (enzyme activity, cell division, and intracellular toxins) and ultrastructure (particularly the gas vesicles) of the cells surviving in the heart of the colony are comparable to those of the planktonic form, with all the potential needed for growth. Maintaining cellular integrity requires a process that can provide sufficient energy and is expressed in the reduced, but still existing, enzymatic activity that we measured, which is equivalent to a quiescent state.
Up‐Regulation of Myocardial L‐Type Ca2+ Channel in Chronic Alcoholic Subjects Without Cardiomyopathy
Authors: Fatjó Francesc , Sancho‐Bru Pau , Fernández‐Solà Joaquim , Sacanella Emilio , Estruch Ramón , Bataller Ramón , Nicolás Josep‐María
Published: May 2007

Background: Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. L‐type Ca2+ channels, involved in excitation–contraction coupling, are disturbed in animal models of persistent ethanol consumption. This study was designed to evaluate the density and function of myocardial L‐type Ca2+ channel receptors in organ donors with chronic alcoholism and controls.

Methods: The protein expression of L‐type Ca2+ channels was determined with 3H‐(+)‐PN 200‐110‐binding experiments using a specific antibody against the α1‐subunit in homogenate samples of left‐ventricle apex from organ donors: healthy controls (n=11), chronic alcoholic without cardiomyopathy (n=12), and alcoholics with cardiomyopathy (n=11). Morphometric measurements of cardiomyocytes were performed.

Results: Binding experiments proved an up‐regulation of L‐type Ca2+ channels expression in alcoholic patients compared with controls (Bmax 2.61 ± 1.10 vs 1.33 ± 0.49 fmol/mg, respectively; p<0.001). This up‐regulation was present in the group of alcoholic subjects without cardiomyopathy, and was not seen in those with cardiomyopathy (3.39 ± 2.20 vs 1.77 ± 0.53 fmol/mg, respectively; p=0.02). The cross‐sectional area and perimeter of the cells were greater in alcoholic patients with cardiomyopathy compared with controls and alcoholic patients without cardiomyopathy (500 ± 87 vs 307 ± 74 and 255 ± 25 μm2, respectively; p<0.001 both) as was the perimeter (78.7 ± 7.7 vs 61.5 ± 7.2 and 56.5 ± 2.8 μm, respectively; p<0.001 both). Binding results did not change after adjusting receptor measurements for cross‐sectional area and cell perimeter.

Conclusions: Chronic alcoholism causes an up‐regulation of myocardial L‐type Ca2+ channel receptors, which decreases when cardiomyopathy is present.
Effects of Ethanol on Midbrain Neurons: Role of Opioid Receptors
Authors: Xiao Cheng , Zhang Jingli , Krnjević Krešimir , Ye Jiang Hong
Published: May 2007

Background:Although ethanol addiction is believed to be mediated by the mesolimbic dopamine system, originating from the ventral tegmental area (VTA), how acute ethanol increases the activity of VTA dopaminergic (DA) neurons remains unclear.

Method:Patch‐clamp recordings of spontaneous firings of DA and GABAergic neurons in the VTA in acute midbrain slices from rats.

Results:Ethanol (20–80 mM) excites DA neurons, and more potently depresses firing of local GABAergic neurons. The ethanol‐induced excitation of DA neurons is considerably attenuated by DAMGO (Tyr‐d‐Ala‐Gly‐N‐Me‐Phe‐Gly‐ol enkephalin), aμ‐opioid agonist that suppresses firing of GABAergic neurons, or by naloxone, a general opioid antagonist. The ongoing opioid‐induced facilitation of DA cell firing (revealed by naloxone) is enhanced by ethanol, probably by an increase in opioid release or action.

Conclusion:Ethanol excites VTA DA neurons at least partly by increasing ongoing opioid‐mediated suppression of local GABAergic inhibition. This indirect mechanism may contribute significantly to the positively reinforcing properties of ethanol.
Mutant Batten Disease Protein Says “No” to Unsaturated Fats
Authors: Gallagher Martin J.
Published: May 2007

CLN3P, the Batten's Disease Protein, Is a Novel Palmitoyl-Protein Δ-9 Desaturase Narayan SB, Rakheja D, Tan L, Pastor JV, Bennett MJ. Ann Neurol 2006;60(5):570–577. OBJECTIVE: Batten's disease, one of the most common recessively inherited, untreatable, neurodegenerative diseases of humans, is characterized by progressive neuronal loss and intraneuronal proteolipid storage. Although the gene for the disorder was cloned more than a decade ago, the function of the encoded protein, CLN3P, has not been defined thus far. METHODS: Sequence analysis using the Pfam server identified a low stringency match to a fatty acid desaturase domain in the N-terminal sequence of CLN3P. We developed a fatty acid desaturase assay based on measurement of desaturase products by gas chromatography/mass spectrometry. RESULTS: We show that CLN3P is a novel palmitoyl-protein Δ-9 desaturase, which converts membrane-associated palmitoylated proteins to their respective palmitoleated derivatives. We have further demonstrated that this palmitoyl-protein Δ-9 desaturase activity is deficient in cln3–/– mouse pancreas and is completely ablated in neuroblastoma cells by RNA inhibition. INTERPRETATION: We propose that palmitoyl-protein desaturation defines a new mechanism of proteolipid modification, and that deficiency of this process leads to the signs and symptoms of Batten's disease.
Two steps to functional mesenchymal stromal cells for clinical application
Authors: Bartmann Christina , Rohde Eva , Schallmoser Katharina , Pürstner Peter , Lanzer Gerhard , Linkesch Werner , Strunk Dirk
Published: May 2007

BACKGROUND: Ex vivo expansion of multipotent mesenchymal stromal cells (MSCs) is a prerequisite for evaluating their therapeutic potential in ongoing clinical trials. Even large volumes of starting material and extended culture periods, however, do not necessarily produce 2 × 106 MSCs per kg per adult patient. A new two‐step procedure has been devised to propagate more than 1 × 108 MSCs from small marrow volumes within fewer than 4 weeks.

STUDY DESIGN AND METHODS: The influence of log fold decreased MSC seeding (2500, 250, 25, 2.5/cm2) on clinical‐scale expansion, MSC phenotype, and immunomodulatory function combined with multiplex cytokine display was analyzed. Maintenance of MSC characteristics was tested in fibroblast colony‐forming unit and differentiation assays.

RESULTS: Reduced seeding density boosted MSC propagation. Low‐density expanded MSCs were CD29+, CD73+, CD90+, CD105+, CD14–, CD34–, CD45–, HLA‐DR–; retained their differentiation potential; and inhibited lymphocyte proliferation. This was accompanied by deregulated cytokine production. Seeding 0.7 × 106 to 1 × 106 MSCs derived from a 10‐ to 13‐day primary culture at a low density of 28 to 40 per cm2 permitted propagation of 1.5 × 108 to 3.7 × 108 functional MSCs within a 13‐ to 15‐day secondary expansion step.

CONCLUSION: Primary seeding of only 10‐mL marrow aspirates on approximately 0.2‐m2 culture area (Step 1) followed by expansion on 2.5 m2 (Step 2) is sufficient to consistently generate at least 1.5 × 108 MSCs in fetal bovine serum–supplemented medium within less than 4 weeks. The efficiency of this two‐step procedure for clinical‐scale MSC propagation may facilitate rational clinical testing of MSC‐based therapies.
Human platelet lysate can replace fetal bovine serum for clinical‐scale expansion of functional mesenchymal stromal cells
Authors: Schallmoser Katharina , Bartmann Christina , Rohde Eva , Reinisch Andreas , Kashofer Karl , Stadelmeyer Elke , Drexler Camilla , Lanzer Gerhard , Linkesch Werner , Strunk Dirk
Published: May 2007

BACKGROUND: Human multipotent mesenchymal stromal cells (MSCs) are promising candidates for a growing spectrum of regenerative and immunomodulatory cellular therapies. Translation of auspicious experimental results into clinical applications has been limited by the dependence of MSC propagation from fetal bovine serum (FBS).

STUDY DESIGN AND METHODS: The capacity of human platelet lysate (HPL) to replace FBS for clinical‐scale MSC propagation was analyzed.

RESULTS: HPL could be efficiently produced from buffy coats. Multiplex analyses allowed a distinct HPL growth factor profile to be delineated. With a previously established two‐step clinical‐scale procedure, HPL was reproducibly more efficient than FBS in supporting MSC outgrowth. With only 3 × 105 primary culture‐derived MSCs, a mean of 4.36 × 108 HPL‐MSCs (range, 3.01 × 108‐5.40 × 108) was obtained within a single secondary 11‐ to 13‐day culture step. Although morphologically distinct, HPL‐MSCs and FBS‐MSCs did not differ significantly in terms of immunophenotype, differentiation potential in vitro, and lack of tumorigenicity in nude mice in vivo.

CONCLUSIONS: Replacing FBS with HPL prevents bovine prion, viral, and zoonose contamination of the stem cell product. This new efficient FBS‐free two‐step procedure for clinical‐scale MSC propagation may represent a major step toward challenging new stem cell therapies.
Cryopreservation of cellular products in a closed‐bag system with an incorporated dimethyl sulfoxide–resistant sterile filter outside of cleanroom facilities
Authors: Humpe Andreas , Jansen Pal , Tischer Bernd Karsten , Schubert Sabine , Beck Christian , Adamzik Ilse‐Dorothea , Maas Jens‐Holger , Strate Alexander , Gramatzki Martin , Riggert Joachim
Published: May 2007

BACKGROUND: Manipulations, for example, cryopreservation, of cellular therapeutics carried out in an open system must be performed in a class A environment with surrounding class B environment. To avoid cleanroom facilities, a new closed‐bag system with an incorporated dimethyl sulfoxide–resistant sterile filter for cryopreservation of cellular products was evaluated at two different centers.

STUDY DESIGN AND METHODS: A total of 44 different products (22 buffy coats [BCs] and 22 leukapheresis [LK] products) were split and cryopreserved in parallel in cleanroom facilities (Method I) and with the closed system on the bench of a “normal” laboratory (Method II). Viability analyzed by 7‐aminoactinomycin D staining and flow cytometric analysis and sterility of the products were analyzed.

RESULTS: Independent of the cellular source (BC or LK), the median viability of CD45+ cells decreased significantly (p  < 0.01) during cryopreservation: namely, in BCs, −15.8 percent with both methods, and in LK products, −5.4 percent with Method I and −4.8 percent with Method II, respectively. CD3+ as well as CD14+ cells exhibited a similar pattern and were also found significantly (p  < 0.01) diminished after thawing independent of the handling system. For CD19+ cells, the small decrease of viability was only for the BC group significant (p = 0.027) when the cells had been processed with Method I. No bacterial contamination was detected neither in fresh products nor in products after cryopreservation.

CONCLUSION: The closed system for cryopreservation of cellular products appears to be equivalent to cleanroom‐based methods regarding cellular integrity and sterility when appropriate quality of sterile filters is assured.
Protein A immunoadsorption therapy for refractory, mitomycin C–associated thrombotic microangiopathy
Authors: Kasper Stefan , Neurath Markus F. , Huber Christoph , Theobald Matthias , Scharrer Inge
Published: May 2007

BACKGROUND: Mitomycin C–associated thrombotic microangiopathy (TMA) has a poor prognosis with limited therapeutic options. Most patients die within 4 months of diagnosis due to pulmonary or renal failure. Here, a patient resistant to total plasma exchange (TPE) and immunosuppressive therapy with glucocorticoids, rituximab, vincristine, and splenectomy who was successfully treated with protein A immunoadsorption is described.

CASE REPORT: A 29‐year‐old woman developed a TMA after chemotherapy with mitomycin C. She presented with thrombocytopenia, pulmonary edema, hemolytic anemia with presence of schistocytes, and renal failure. Immediate TPE (>120 times) and immunosuppressive therapy with glucocorticoids, however, did not improve her clinical situation. Furthermore, she was refractory to subsequent immunosuppressive therapy with rituximab and vincristine and laparoscopic splenectomy. Finally, after 12 cycles of extracorporeal protein A immunoadsorption with a commercially available immunoadsorption system (Immunosorba, Fresenius AG), platelet counts increased with disappearance of hemolytic syndromes.

CONCLUSION: Extracorporeal protein A immunoadsorption with the Immunosorba system emerges as a potentially effective and safe treatment for refractory mitomycin C–associated TMA with only moderate side effects. This therapeutic option may be considered at an early state of the disease to prevent extensive immunosuppression.
Occurrence and severity of adverse events after autologous hematopoietic progenitor cell infusion are related to the amount of granulocytes in the apheresis product
Authors: Calmels Boris , Lemarié Claude , Esterni Benjamin , Malugani Caroline , Charbonnier Aude , Coso Diane , Schiano de Colella Jean‐Marc , Deconinck Eric , Caillot Denis , Viret Frédéric , Ladaique Patrick , Lapierre Valérie , Chabannon Christian
Published: May 2007

BACKGROUND: Adverse events (AEs) after hematopoietic progenitor cell (HPC) infusion are rare but might be life‐threatening. These reactions have traditionally been associated with the amount of infused cryoprotectant, but persistence of such events after dimethyl sulfoxide (DMSO) depletion has questioned this assumption.

STUDY DESIGN AND METHODS: The incidence of AEs on a cohort of 460 patients (490 HPC infusions) undergoing autologous DMSO‐reduced HPC transplantation was prospectively evaluated. HPCs were collected from adult patients with various hematologic or solid malignancies. After quality control (QC) on fresh apheresis products and subsequent cryopreservation, HPC grafts were thawed and washed at the cell therapy facility. QC was performed on each graft after washing, and clinical data were collected for each infusion.

RESULTS: AEs were reported in 66 cases (13.5%) and were graded according to the NCI‐CTC scale from 1 to 4. Although none of the factors associated with patient characteristics or infusion procedure were different between the two groups (no AE vs. occurrence of AE), it was found that the absolute number of granulocytes measured before freezing was considerably higher in the AE group. Furthermore, within this group, there was a strong correlation between the amount of granulocytes and the grading of the reaction.

CONCLUSION: This survey demonstrates that AEs occurring in the setting of DMSO‐reduced HPC grafts are directly related to the amount of granulocytes and thus emphasizes the need for high‐quality apheresis products so as to improve the safety of HPC infusion.
Nonleukoreduced red blood cell transfusion induces a sustained inhibition of neutrophil chemotaxis by stimulating in vivo production of transforming growth factor‐β1 by neutrophils: role of the immunoglobulinlike transcript 1, sFasL, and sHLA‐I
Authors: Ottonello Luciano , Ghio Massimo , Contini Paola , Bertolotto Maria , Bianchi Giordano , Montecucco Fabrizio , Colonna Marco , Mazzei Clemente , Dallegri Franco , Indiveri Franco
Published: May 2007

BACKGROUND: Red blood cell (RBC) transfusion has been linked to increased susceptibility to infections in critically ill patients and to augmented incidence of postoperative infections. The mechanisms by which transfusions can induce immunosuppression are only partially defined. Recently, it has been demonstrated that RBC supernatants inhibit neutrophil migration. Such inhibitory activity is due to transforming growth factor (TGF)‐β1 contained in the supernatants that desensitize neutrophils to subsequent chemotaxic stimulation.

STUDY DESIGN AND METHODS: In ancillary experiments, it was observed that plasma from transfused patients maintained its capacity of inhibiting neutrophil chemotaxis several days after RBC transfusion. Thus, this study was planned to investigate the mechanism(s) responsible for the prolonged inhibition of neutrophil chemotaxis observed after RBC transfusion.

RESULTS: Plasma samples obtained from subjects who underwent RBC transfusion display a capability of inhibiting neutrophil chemotaxis, which is detectable up to 15 days after the transfusion. The inhibition is related to the capacity of FasL and HLA‐I molecules contained in RBC supernatants to induce in vivo TGF‐β1 synthesis by neutrophils. The induction of TGF‐β1 secretion in neutrophils by HLA‐I molecules depends on immunoglobulinlike transcript 1/CD85 triggering.

CONCLUSION: The property of RBC transfusion of inducing a sustained inhibition of neutrophil chemotaxis seems to be a potential mechanism that concurs to the susceptibility to infections in patients who receive transfusions. Furthermore, our findings, showing neutrophil production of TGF‐β1 in response to FasL and HLA‐I molecules, confirm that neutrophils are endowed not only with effector functions but also with immunomodulatory properties possibly involved in the regulation of inflammatory processes.
Genotype probabilities of pairs of individuals for X‐chromosome markers
Authors: Toni Chiara , Domenici Ranieri , Presciuttini Silvano
Published: May 2007

BACKGROUND: The usual set of autosomal markers (A‐STRs) available in commercial kits is often insufficient to discriminate between close relationships when only two subjects are available for analysis. X‐chromosome markers (X‐STRs) provide higher statistical power in special cases.

STUDY DESIGN AND METHODS: Formulas are derived for the probabilities of all possible genotype pairs for X‐STRs of any sex combination for seven common relationships. The power of exclusion (PE) of X‐STRs in parentage analysis is compared with that of A‐STRs of equivalent distribution of allele frequency.

RESULTS: Seventy‐three equations were obtained, from which the likelihood ratio of any two alternative hypotheses about the relationship between two individuals can be obtained by division and simplification. For father‐daughter and mother‐son duos, the PE of X‐STRs is almost twice the corresponding value of A‐STRs for moderately low values of heterozygosity (0.6‐0.75); for alleged pairs of sisters and pairs of half‐sisters the PE is equivalent to that of A‐STRs in parent‐child duos. Considering four real unlinked X‐STRs, the cumulative PE for father‐daughter and mother‐son duos was 99 percent, compared with 94 percent if they were autosomal.

CONCLUSIONS: X‐STRs can substantially increase the discrimination capacity of standard A‐STRs in parentage analyses involving pairs of individuals. Up to four unlinked X‐STRs may be treated as independent loci. When linked loci are included, computer programs that calculate pedigree likelihoods can be used.
Identification and quantification of fetal red blood cells in maternal blood by a dual‐color flow cytometric method: evaluation of the Fetal Cell Count kit
Authors: Porra Valérie , Bernaud Janine , Gueret Pierre , Bricca Pascaline , Rigal Dominique , Follea Gilles , Blanchard Dominique
Published: May 2007

BACKGROUND: As an alternative to the cumbersome Kleihauer‐Betke test (KBT), flow cytometry represents a powerful method for the identification and quantification of fetal red blood cells (RBCs) in maternal circulation.

STUDY DESIGN AND METHODS: The aim of this study was to evaluate the Fetal Cell Count kit (IQ Products), an innovative flow cytometric method, based on the combination of antibodies directed, respectively, against fetal hemoglobin (HbF) and carbonic anhydrase (CA), a marker expressed after birth, to discriminate fetal RBCs from adult F cells containing HbF. The investigation was performed by two French laboratories that compared the data obtained by flow cytometry and KBT in 455 pregnant or just‐delivered women as well as in 124 artificial mixtures containing from 0.01 to 5.00 percent cord cells.

RESULTS: The FL1/FL2 histogram allowed distinction between fetal RBCs (HbF+, CA–), F cells (HbF+, CA+), and adult RBCs (HbF–, CA+). The limits of detection and quantification were determined at 0.03 and 0.10 percent or 0.02 and 0.05 percent when analyzing 100,000 or 200,000 events, respectively. Linearity was demonstrated between 0.01 and 5.00 percent fetal cells in the mixtures (r = 0.95, p < 0.01). A good correlation between fluorescence‐activated cell sorting (FACS) and KBT results was obtained with artificial mixtures (r = 0.94, p < 0.01). From the 405 Kleihauer‐negative samples, none were identified as positive by FACS. Among the 50 Kleihauer‐positive samples, 6 were shown not to contain fetal cells but F cells by FACS.

CONCLUSION: With this new dual‐color flow cytometric method, accurate evaluation of fetomaternal hemorrhage was achieved even in the face of HbF of maternal origin.
Do patients with autoantibodies or clinically insignificant alloantibodies require an indirect antiglobulin test crossmatch?
Authors: Lee Edmond , Redman Martin , Burgess Gordon , Win Nay
Published: May 2007

BACKGROUND: Compatibility testing is the standard protocol that identifies suitable blood for patients requiring transfusion. If the antibody screen is negative or no clinically significant antibodies are detected, BCSH guidelines and AABB standards allow an immediate‐spin crossmatch (IS XM) or even electronic issue. The testing requirement is less clear where autoantibodies or non–clinically significant alloantibodies compromise the indirect antiglobulin test crossmatch (IAT XM). Performing an IAT XM will give a mismatched result anyway, delays the supply of blood to the patient, and provides no additional benefit or safety.

STUDY DESIGN AND METHODS: From January 2002 to April 2006, the provision of blood for autoimmune hemolytic anemia (AIHA) patients with autoantibodies and no alloantibodies as well as patients with alloantibodies that exhibited a “high‐titer, low‐avidity” (HTLA) mode of reactivity was reviewed.

RESULTS: A total of 222 AIHA patients (428 samples) with autoantibodies had 1585 units of red cells supplied after IAT XM; 1308 (82.5%) were mismatched. In 50 patients (80 samples) with HTLA‐like antibodies, 286 units of 328 (87.2%) were mismatched by IAT XM.

CONCLUSION: No adverse reactions were reported for the study groups where “suitable” blood was provided after a serologically mismatched IAT XM. No additional benefit for these patients can be claimed by performing an IAT XM over an IS XM, as a check of ABO match. The IAT XM is both costly and time‐consuming. It is proposed that for these study group patients, a reduction to an IS XM can be applied and can be beneficial.
Two missense mutations in the CD44 gene encode two new antigens of the Indian blood group system
Authors: Poole Joyce , Tilley Louise , Warke Nicole , Spring Frances A. , Overbeeke Marijke A.M. , Van Der Mark‐Zoet José A.C.M. , Ahrens Norbert , Armstrong Diane , Williams Mark , Daniels Geoff
Published: May 2007

BACKGROUND: Blood samples were referred over a 10‐year period from five patients whose serum samples contained antibodies to unidentified high‐incidence antigens. Three patients (A, B, C) were of Moroccan origin and their antibodies and red blood cells (RBCs) were mutually compatible, but incompatible with those of the other two patients (D, E), who were of Pakistani origin. The antibodies and RBCs of D and E were mutually compatible, but incompatible with those of Patients A, B, and C. All the antibodies were detected during pregnancy.

STUDY DESIGN AND METHODS: Serologic tests, including the use of enzyme‐treated and chemically modified RBCs, suggested a relationship to CD44 (Indian blood group system). The monoclonal antibody immobilization of erythrocyte antigens (MAIEA) assay with monoclonal CD44 antibodies, immunoblotting of RBC membranes, and CD44 gene sequencing were carried out.

RESULTS: Positive reactions in the MAIEA assay confirmed that the patients' antibodies are directed at CD44. Immunoblotting with two of the antibodies gave positive reactions of identical size to monoclonal anti‐CD44 and failed to react with the RBCs of a CD44‐deficient patient. One of the antibodies reacted with purified CD44. Sequencing of Exons 1 to 5 of CD44 revealed 255C>G in Exon 3 for A, B, and C encoding H85Q and 488C>A in Exon 5 for D and E encoding T163R.

CONCLUSION: Two novel CD44 antigens of high incidence have been identified: IN3 (INFI) and IN4 (INJA) in the IN (Indian) blood group system. Lack of IN3 and IN4 results from homozygosity for mutations encoding H85Q and T163R in CD44, respectively.
Shock and Awe vs. Hearts and Minds at the Movies
Authors: GARDELS NATHAN , MEDAVOY MIKE
Published: May 2007

In the age of globalization we are no longer home alone. Migration brings other worlds into our own just as the global reach of the mass media transmits our world into the hearts and minds of others. The resulting clashes and fusions are shaping the soul of the first global civilization in the making.

In this section, one of Hollywood's top producers, Mike Medavoy, and the Oscar‐nominated director of Babel, Alejandro González Iñárritu share their thoughts with NPQ.
North Korea Accord Is a Model for Iranian Crisis
Authors: BLIX HANS
Published: May 2007

As the Soviet Union collapsed and China shifted to the market, it was said that communism was nothing more than the longest road between capitalism and capitalism. It now looks like the Bush‐era neo‐conservatism is similarly a long road back to the realism from whence it departed. The US is now talking with North Korea and Iran instead of preempting them through war.

A dissident Iranian scientist, the former top UN arms inspector and a former US secretary of state ponder this state of affairs.
The Cost of the Last Six Years, From North Korea to Kosovo
Authors: ALBRIGHT MADELEINE
Published: May 2007

As the Soviet Union collapsed and China shifted to the market, it was said that communism was nothing more than the longest road between capitalism and capitalism. It now looks like the Bush‐era neo‐conservatism is similarly a long road back to the realism from whence it departed. The US is now talking with North Korea and Iran instead of preempting them through war.

A dissident Iranian scientist, the former top UN arms inspector and a former US secretary of state ponder this state of affairs.
The Efficacy of Inducibility and Circumferential Ablation with Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation
Authors: CHANG SHIH‐LIN , TAI CHING‐TAI , LIN YENN‐JIANG , WONGCHAROEN WANWARANG , LO LI‐WEI , TUAN TA‐CHUAN , UDYAVAR AMEYA R. , CHANG SHENG‐HSIUNG , TSAO HSUAN‐MING , HSIEH MING‐HSIUNG , HU YU‐FENG , CHEN YI‐JEN , CHEN SHIH‐ANN
Published: May 2007

Introduction: Some conflicting results of the efficacy of the inducibility test used in the catheter ablation of atrial fibrillation (AF) have been reported. The aim of this study was to investigate the inducibility and efficacy of circumferential ablation with pulmonary vein isolation (PVI) in patients with paroxysmal AF and its relationship to the atrial substrate.

Methods and Results: This study consisted of 88 patients with paroxysmal AF who underwent catheter ablation. Electroanatomic mapping using a NavX system was performed and the biatrial voltage was obtained during sinus rhythm. After successful circumferential ablation with PVI, an inducibility test was performed to determine the requirement for creating left atrial (LA) ablation line. After procedure, patients with inducible AF had a higher recurrence rate than did those with noninducibility of AF (55% vs 18%, P = 0.02). The patients with inducible AF after the PVI had a lower biatrial voltage than did those with negative inducibility. The patients with inducible AF after the final procedure who had a recurrence had a lower LA voltage (1.3 ± 0.4 vs 1.8 ± 0.4 mV, P = 0.02) and longer LA total activation time (99 ± 18 vs 88 ± 13 msec, P = 0.02) than did those with noninducible AF and no recurrence. None of the patients had occurrence of LA flutter during the follow‐up.

Conclusion: After a single procedure of circumferential ablation with PVI and noninducibility, 82% patients did not have recurrence of AF. The inducibility of AF was related to the recurrence of AF. The atrial substrate affected the outcome of the inducibility.
Direct Ultrasound Measurement of Longitudinal, Circumferential, and Radial Strain Using 2‐Dimensional Strain Imaging in Normal Adults
Authors: Hurlburt Heather M. , Aurigemma Gerard P. , Hill Jeffrey C. , Narayanan Arumugam , Gaasch William H. , Vinch Craig S. , Meyer Theo E. , Tighe Dennis A.
Published: May 2007

Current noninvasive techniques used to evaluate left ventricular systolic function are limited by dependence on the angle of insonation (tissue Doppler imaging/TDI) or limited by availability (MRI tagging). We utilized 2‐dimensional speckle strain (ε) imaging (1) to establish normal values for all three ε vectors; (2) to compare circumferential ε values with circumferential shortening (midwall fractional shortening (FSmw); (3) to examine the relationship between left ventricular ε and wall stress; and (4) to compare 2D echocardiographic characteristics by gender. Echocardiography was performed in 60 normal subjects (mean 39 ± 15 years). Small, but significant regional heterogeneity was seen in circumferential ε, but not in radial or longitudinal ε. We found an inverse correlation between circumferential ε and stress (r =−0.29, p<0.05) as well as longitudinal ε and stress (r =−0.11, P < 0.05), though the relationships were not close. We also observed a linear relationship between mean circumferential ε and FSmw (r = 0.29, P < 0.05). In conclusion, (1) 2‐dimensional ε imaging permits measurement of regional systolic ε values in the majority of normal individuals; (2) ε values furnished by this method obey expected stress‐shortening relationships; (3) systolic ε displays minor regional heterogeneity in the circumferential direction; (4) for the first time, a close relationship between FSmw and mean circumferential ε was demonstrated; and (5) there are minor gender‐related differences in LV geometry and function.
Noninvasive Assessment of Coronary Flow Reserve in the Left Anterior Descending Artery by Transthoracic Echocardiography before and after Stenting
Authors: Chammas Elie , Dib Chadi , Rahhal Maya , Helou Toni , Ghanem Georges , Tarcha Walid
Published: May 2007

Background: Noninvasive assessment of coronary flow reserve in the left anterior descending artery (LAD) by transthoracic Doppler echocardiography (TTDE) has been already validated as a new method for determining the degree of stenosis over the proximal flow. Objectives: The aim of the study is to determine, by TTDE, the feasibility and the value of the coronary flow reserve (CFR) (defined as the maximal increase in coronary blood flow above its basal pressure for a given perfusion pressure when coronary circulation is maximally dilated) in the mid‐to‐distal LAD before and after percutaneous angioplasty and to demonstrate the early recovery of microvascular tone immediately after stenting. Methods: The study population consisted of 36 patients with significant isolated LAD stenosis (70–90%) identified by coronary angiography. CFR was recorded in the mid‐to‐distal LAD at rest and during hyperemia obtained after adenosine intravenous infusion before and after stenting. Results: Adequate visualization of the LAD was obtained in 25 out of 36 patients (70%). At rest the mean CFR was 1.5132 ± 0.33 (1.1–2.58). However, after stenting the mean CFR was significantly higher: 2.18 ± 0.55 (1.3–3.8), with P <0.01. Conclusions: CFR can be easily determined by TTE in approximately 70% of patients. Noninvasive Doppler echocardiography shows impaired CFR in patients with LAD disease. After stenting CFR is restored, demonstrating early recovery of microvascular tone. These results are comparable to those published in the same conditions. Larger series with a long‐term follow‐up may allow identifying patients at high risk for restenosis after stenting.
Right Ventricular Function in Patients with Beta Thalassemia: Relation to Serum Ferritin Level
Authors: Hamdy Amal M. , Zein El‐Abdin Maha Y. , Abdel‐Hafez Manal A.
Published: May 2007

Cardiac dysfunction is a major cause of death in patients with beta thalassemia. Right ventricular (RV) contribution to cardiac morbidity and mortality in these patients has been suggested. We aimed to assess RV function in beta thalassemia (β‐Th) patients and to detect the relation of serum ferritin level to RV dysfunction. Thirty young patients with β‐Th and 15 age‐matched normal subjects (NL) were included. We measured RV end diastolic and end systolic diameters (RVEDD and RVESD), RV % fractional shortening (RVFS), RV pressure (RVP), lateral and septal tricuspid annular systolic and diastolic tissue Doppler velocities (Sa, Ea, Aa & Ea/Aa), and RV myocardial systolic and diastolic velocities at the basal RV segment (RVSm, RVEm, RVAm & RVEm/Am). Serum ferritin level was measured in β‐Th patients who were divided accordingly into two groups; G1 with serum ferritin ≥2,000 ug/L and G2 with serum ferritin <2,000 ug/L. Compared to NL subjects, β‐Th patients had significantly higher RVEDD, RVESD & RVP, lower RVFS, higher Aa, and lower Ea/Aa at lateral and septal tricuspid annular sites, higher RVAm and lower RVEm/Am. Patients with higher serum ferritin level (G1) had higher RVP, higher RVEDD and RVESD, lower Sa at the lateral annular site and lower RVSm than patients in G2. High serum ferritin level was significantly associated with pulmonary hypertension. We concluded that patients with β‐Th have RV diastolic dysfunction, pulmonary hypertension is common, and the presence of RV systolic dysfunction in these patients is related to the higher level of serum ferritin.