bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative intravenous iron, with or without erythropoietin, plus restrictive transfusion protocol reduce the need for allogeneic blood after knee replacement surgery
Authors: Cuenca Jorge , García‐Erce José A. , Martínez Fernando , Pérez‐Serrano Luis , Herrera Antonio , Muñoz Manuel
Published: June 2006

BACKGROUND:  Unilateral total knee replacement (TKR) results in a substantial blood loss and 30 to 50 percent of patients receive allogeneic blood transfusion (ABT). Therefore, the effectiveness of a restrictive transfusion trigger (hemoglobin [Hb] level < 8 g/dL) plus stimulation of erythropoiesis was evaluated, with or without blood salvage, for reducing ABT in TKR patients.

STUDY DESIGN AND METHODS:  A series of 139 consecutive of primary TKR patients received perioperative iron sucrose (2 × 200 mg/48 hr, intravenously [IV]), plus preoperative erythropoietin (EPO; 1 × 40.000 UI, sc) if preoperative Hb level was less than 130 g per L (Group A). This protocol was applied to another series of 173 consecutive TKR patients who also received postoperative unwashed shed blood (USB) if preoperative Hb level was less than 130 g per L (Group B). Perioperative clinical and laboratory data were gathered.

RESULTS:  No adverse effects of iron sucrose, EPO, or USB administration were witnessed, and only 13 patients received ABT overall (4%). No major differences in perioperative blood counts or iron metabolism variables were observed between groups, but stimulation of erythropoiesis seemed to be more pronounced in those patients receiving EPO (p < 0.05). There were no differences in postoperative complications between groups, but length of hospital stay for patients with a preoperative Hb level of less than 130 g per L was shorter in Group B (p < 0.05).

CONCLUSION:  This blood saving protocol seems to be effective for reducing ABT in TKR patients. Which patients are more likely to benefit from either perioperative iron administration or selective addition of postoperative blood salvage to pharmacologic treatment, however, needs to be further evaluated.
Removal of small nonenveloped viruses by antibody‐enhanced nanofiltration during the manufacture of plasma derivatives
Authors: Kreil Thomas R. , Wieser Andreas , Berting Andreas , Spruth Martin , Medek Christian , Pölsler Gerhard , Gaida Theodor , Hämmerle Thomas , Teschner Wolfgang , Schwarz Hans Peter , Barrett P. Noel
Published: June 2006

BACKGROUND:  Filters with nominal pore sizes in the nanometer range are well‐established tools for enhancing the virus safety margins of plasma‐derived products, yet intrinsically less successful for smaller viruses such as hepatitis A virus (HAV) and human parvovirus B19 (B19V). The formation of virus‐antibody complexes increases the effective size of these smaller viruses and would thus improve their removal by nanofiltration. While the principle of virus removal by antibody‐dependent nanofiltration has been demonstrated with animal antisera and viruses spiked into human plasma product intermediates, the significance of these results remains unclear due to the potential contributions of xenoanti‐bodies and/or heteroagglutination in such heterologous systems.

STUDY DESIGN AND METHODS:  The current study investigated antibody‐dependent virus removal by nanofiltration in a heterologous animal parvovirus system to establish the concentration dependence of the effect. In addition, the phenomenon was investigated in a homologous system with custom‐made HAV and B19V antibody–free and ‐containing human immunoglobulin intermediates. Viruses were analyzed with infectivity assays and fully validated polymerase chain reaction assays that also circumvent the obscuring effects of neutralizing antibodies with infectivity assays.

RESULTS:  By use of the heterologous mice minute virus and the homologous HAV and B19V systems, viruses passed the 35‐nm (Planova 35N) filter in the absence of specific antibodies. Beyond a threshold virus antibody concentration, nanofiltration resulted in effective virus removal of viruses smaller than the nominal pore size of the filter used.

CONCLUSION:  HAV and B19V are effectively removed by antibody‐dependent 35N nanofiltration, already at intermediate antibody concentrations well below those comparable to human plasma pools for fractionation.
Different behavior of erythrovirus B19 and torquetenovirus in response to a single step of albumin purification
Authors: Azzi Alberta , Maggi Fabrizio , Zakrzewska Krystyna , Menconi Maria Carla , Di Pietro Niccolò , Salotti Vittorio , Farina Claudio , Andreoli Elisabetta , Fiorentino Bruno , Angelini Cristina , Corcioli Fabiana , Bendinelli Mauro
Published: June 2006

BACKGROUND:  The safety of human serum albumin (HSA) is of special interest with respect to virus transmission because of the wide use of this blood product as a therapeutic agent and also, added to other products, as an excipient or a stabilizer. Conflicting data are reported concerning HSA contamination by small, naked viruses such as the erythrovirus B19 (B19V) and the anellovirus torquetenovirus (TTV). This study has been performed to assess the effect of the HSA purification procedures on the viral contamination.

STUDY DESIGN AND METHODS:  Known concentrations of B19V and TTV virus were spiked in raw Fraction V, the starting material from fractionated human plasma for HSA purification, which was subsequently submitted to the depth filtration procedure. After spiking, B19V and TTV genome copies were determined by real‐time quantitative polymerase chain reaction assays in the mixture at the end of Fraction V dissolution, to determine the virus concentration achieved, in the HSA solution after the filtration step, in the filtered postwashing fluid, and in the supernatant of resuspended Celite.

RESULTS:  B19V was completely adsorbed by the Celite used as a filter aid in the depth filtration process and was thus undetectable in the resulting HSA‐containing fraction. In contrast, in 2 out of 3 experiments, TTV was detected in all samples.

CONCLUSION:  The different behavior of the two viruses might be a reflection of their different surface charge.
Photochemical treatment of plasma with amotosalen and long‐wavelength ultraviolet light inactivates pathogens while retaining coagulation function
Authors: Singh Yasmin , Sawyer Lynette S. , Pinkoski Linda S. , Dupuis Kent W. , Hsu Jocelyn C. , Lin Lily , Corash Laurence
Published: June 2006

BACKGROUND:  The INTERCEPT Blood System, a photochemical treatment (PCT) process, has been developed to inactivate pathogens in platelet concen‐trates. These studies evaluated the efficacy of PCT to inactivate pathogens in plasma and the effect of PCT on plasma function.

STUDY DESIGN AND METHODS:  Jumbo (600 mL) plasma units were inoculated with high titers of test pathogens and treated with 150 µmol per L amotosalen and 3 J per cm2 long‐wavelength ultraviolet light. The viability of each pathogen before and after treatment was measured with biological assays. Plasma function was evaluated through measurement of coagulation factors and antithrombotic protein activities.

RESULTS: The levels of inactivation expressed as log‐reduction were as follows: cell‐free human immunodeficiency virus‐1 (HIV‐1), greater than 6.8; cell‐associated HIV‐1, greater than 6.4; human T‐lymphotropic virus‐I (HTLV‐I), 4.5; HTLV‐II, greater than 5.7; hepatitis B virus (HBV) and hepatitis C virus, greater than 4.5; duck HBV, 4.4 to 4.5; bovine viral diarrhea virus, 6.0; severe acute respiratory syndrome coronavirus, 5.5; West Nile virus, 6.8; bluetongue virus, 5.1; human adenovirus 5, 6.8; Klebsiella pneumoniae, greater than 7.4; Staphylococcus epidermidis and Yersinia enterocolitica, greater than 7.3; Treponema pallidum, greater than 5.9; Borrelia burgdorferi, greater than 10.6; Plasmodium falciparum, 6.9; Trypanosoma cruzi, greater than 5.0; and Babesia microti, greater than 5.3. Retention of coagulation factor activity after PCT was expressed as the proportion of pretreatment (baseline) activity. Retention was 72 to 73 percent of baseline fibrinogen and Factor (F)VIII activity and 78 to 98 percent for FII, FV, FVII, F IX, FX, FXI, FXIII, protein C, protein S, antithrombin, and α2‐antiplasmin.

CONCLUSION: PCT of plasma inactivated high levels of a wide range of pathogens while maintaining adequate coagulation function. PCT has the potential to reduce the risk of transfusion‐transmitted diseases in patients requiring plasma transfusion support.
In vitro variables of red blood cell components collected by apheresis and frozen 6 and 14 days after collection
Authors: Grose Heather L. , Byrne Karen M. , Salata Jeanne M. , Rentas Francisco J. , Stroncek David F.
Published: June 2006

BACKGROUND:  An automated cell processing system (ACP 215, Haemonetics Corp.) can be used for the glycerolization and deglycerolization of RBC components, but the components must be 6 or fewer days old. Depending on the anticoagulant (CP2D)/additive solution (AS) used, deglycerolized RBCs can be stored at 1 to 6°C for up to 14 days. This study evaluated in vitro variables of apheresis RBC stored for 6 and 14 days at 1 to 6°C before glycerolization and 14 days after deglycerolization.

STUDY DESIGN AND METHODS:  Two units of CP2D/AS‐3 leukoreduced RBCs were collected by apheresis from seven donors. One unit was glycerolized and frozen 6 days and the other 14 days after collection. All units were deglycerolized with the ACP 215 and stored at 1 to 6°C for 14 days in AS‐3. Several in vitro variables were evaluated during postdeglycerolization storage.

RESULTS:  All components had postdeglycerolization RBC recoveries greater than 81 percent and osmolalities of less than 400 mOsm per kg. No significant differences were noted in potassium and supernatant hemoglobin after 14 days of postdeglycerolization storage between RBCs frozen at 6 and 14 days after collection. After 14 days of postdeglycerolization storage, however, the pH, lactate, and ATP levels were slightly lower in RBCs frozen after 14 days.

CONCLUSION:  The ACP 215 can be used to glycerolize and deglycerolize apheresis RBC components that are up to 14 days of age. It is likely that apheresis components glycerolized at 14 days of age or less can be stored up to 14 days in AS‐3 after deglycerolization, but this should be confirmed with in vivo survival studies.
A simple and practical assay for the antigen‐specific detection of platelet antibodies
Authors: Meyer Oliver , Agaylan Ashraf , Borchert Hans‐Hubert , Aslan Tunay , Bombard Stephane , Kiesewetter Holger , Salama Abdulgabar
Published: June 2006

BACKGROUND:  The antigen‐specific assays currently used for characterization of platelet (PLT)‐reactive auto‐ and alloantibodies are too technically complex and impracticable for most routine laboratories. Here, a novel antigen‐specific particle assay (ASPA) for PLTs similar to that of red blood cells is described.

STUDY DESIGN AND METHODS:  PLTs were solubilized and then incubated with red‐dyed polystyrene particles coated with monoclonal antibodies (MoAbs) to various PLT glycoprotein complexes. These particles were directly tested for coating with autoantibodies (n = 8) or indirectly tested for serum autoantibodies (n = 33) or alloantibodies against HPA‐1a (n = 4) or HPA‐5b (n = 5). Serum samples from healthy blood donors (n = 100) served as negative controls.

RESULTS:  Negative reactions were clearly distinguishable from positive reactions, and the results of the particle assay were in concordance with those obtained by the standard MoAb‐specific immobilization of PLT antigen assay (MAIPA) in all cases with alloanti‐bodies. In three patients, only the ASPA was able to detect autoantibodies that were completely undetectable by the MAIPA. In contrast, in only one patient, the MAIPA detected autoantibodies that the ASPA failed to detect.

CONCLUSION:  In our opinion, the new ASPA is reliable, yet less complex and time‐consuming than the currently available assays, and it can be implemented in any routine laboratory.
Macular recovery after retinal detachment
Authors: Abouzeid Hana , Wolfensberger Thomas J.
Published: June 2006

Macular recovery after surgery for retinal detachment (RD) depends on preoperative and postoperative predictive factors. Preoperative visual acuity is the main preoperative factor correlating positively with good macular recovery. Preoperative factors, which influence macular recovery negatively, include duration of macular detachment, height of macular detachment and vitreomacular traction. Postoperative factors, which influence macular recovery negatively, include cystoid macular oedema, epiretinal membranes, retinal folds, subretinal retinal pigment epithelium (RPE) migration and persistent subretinal fluid on optical coherence tomography (OCT). According to the latest available data, a detached macula has to be reattached within 5 days to optimize functional recovery. However, new therapeutic options such as exposure to hyperoxia or different growth factors may help to improve the final visual outcome in the presence of an already detached macula.
Optical coherence tomography: a key to the future management of patients with diabetic macular oedema
Authors: Massin Pascale , Girach Aniz , Erginay Ali , Gaudric Alain
Published: June 2006

Diabetic macular oedema is a major cause of visual loss in patients with diabetes. It usually results from the breakdown of the inner blood–retinal barrier. Early detection of retinal abnormalities is vital in preventing diabetic macular oedema and subsequent loss of vision, whilst assessment of retinal thickness is important for treatment and follow‐up. Until recently, however, the methods available for detecting and evaluating diabetic macular oedema were slit‐lamp biomicroscopy and stereoscopic photography, both of which are limited in detecting earlier retinal changes. Optical coherence tomography (OCT) is a new diagnostic imaging modality that provides high‐resolution, cross‐sectional images of the eye. It is proving to be an accurate tool for the early diagnosis, analysis and monitoring of retinopathy, with high repeatability and resolution. It allows not only the qualitative diagnosis of diabetic macular oedema, but also the quantitative assessment of oedema. This article reviews the future role of OCT in the management of patients with diabetic macular oedema.
MRI volumetric and 31PMRS metabolic correlates of caudate nucleus in antipsychotic‐naïve schizophrenia
Authors: Jayakumar P. N. , Venkatasubramanian G. , Keshavan M. S. , Srinivas J. S. , Gangadhar B. N.
Published: June 2006

Objective: To examine the volumetric and metabolic correlates of caudate nucleus in antipsychotic‐naïve schizophrenia patients in comparison with healthy controls.

Method: Twelve antipsychotic‐naïve schizophrenia patients and 13 healthy controls underwent31P magnetic resonance spectroscopy of basal ganglia. Magnetic resonance imaging volume of caudate nuclei was measured usingscion imagesoftware.

Results: Patients had significantly smaller caudate volume than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total adenosine tri‐phosphate ratios of both caudate nuclei were significantly lower in patients than controls. Significant negative correlation was found between the left caudate volume and left PCr/total phosphorus ratio in the patients. Age at onset of psychosis had i) significant negative correlation with right and left caudate volumes and ii) significant positive correlation with left PCr/total phosphorus ratio.

Conclusion: The metabolic and volumetric abnormalities of caudate nucleus in antipsychotic‐naïve schizophrenia patients support neurodevelopmental etiopathogenesis.
Is psychosis in DSM‐IV mania due to severity? The relevance of selected demographic and comorbid social‐phobic features
Authors: Azorin J.‐M. , Akiskal H. , Akiskal K. , Hantouche E. , Châtenet‐Duchêne L. , Gury C. , Lancrenon S.
Published: June 2006

Objective: We tested whether factors other than episode severity contributed to psychosis in mania.

Method: Psychiatrists collected systematic clinical data on 1090 hospitalized DSM‐IV manic patients in France, and completed the Mania Rating Scale (MRS) and the Scale for the Assessment of Positive Symptoms (SAPS).

Results: Using DSM‐IV specifiers, 21.9% were non‐severe, 28.2% severe without psychosis, and 49.9% severe with psychosis. On the MRS, patients with psychosis scored significantly higher (P < 0.0001) than non‐severe, but did not differ from the severe without psychosis. We found significant correlations between both the Hallucination and the Delusion subscores of the SAPS and the MRS, as well as correlations between age, single marital status, comorbid social phobia and psychotic mania.

Conclusion: Apart from episode severity, social isolation – associated with younger age, single marital status and social phobia – seems to make a contribution to the origin of manic psychosis largely independent from such severity.
Understanding suicidal ideation in psychosis: findings from the Psychological Prevention of Relapse in Psychosis (PRP) trial
Authors: Fialko L. , Freeman D. , Bebbington P. E. , Kuipers E. , Garety P. A. , Dunn G. , Fowler D.
Published: June 2006

Objective:  To examine the clinically important phenomenon of suicidal ideation in psychosis in relation to affective processes and the multidimensional nature of hallucinations and delusions.

Method:  In a cross‐sectional study of 290 individuals with psychosis, the associations between level of suicidal ideation, affective processes, positive symptoms, clinical and demographic variables were examined.

Results:  Forty‐one per cent of participants expressed current suicidal ideation. Suicidal ideation was associated with depressed mood, anxiety, low self‐esteem, negative illness perceptions, negative evaluative beliefs about the self and others and daily alcohol consumption. Frequency of auditory hallucinations and preoccupation with delusions were not associated with suicidal ideation; however, positive symptom distress did relate to suicidal thoughts.

Conclusion:  Affective dysfunction, including distress in response to hallucinations and delusions, was a key factor associated with suicidal ideation in individuals with psychotic relapse. Suicidal ideation in psychosis appears to be an understandable, mood‐driven process, rather than being of irrational or ‘psychotic’ origin.
The Basel early‐detection‐of‐psychosis (FEPSY)‐study – design and preliminary results
Authors: Riecher‐Rössler A. , Gschwandtner U. , Aston J. , Borgwardt S. , Drewe M. , Fuhr P. , Pflüger M. , Radü W. , Schindler Ch. , Stieglitz R.‐D.
Published: June 2006

Objective:  Early detection and therapy of schizophrenic psychoses have become broadly accepted aims in psychiatry, recently even in very early stages of the disorder when clear diagnostic criteria are not yet fulfilled. However, reliable and widely applicable methods do not yet exist. This study aims at contributing to the improvement of the early assessment of psychosis.

Method:  Individuals potentially at risk are identified by a newly developed stepwise screening procedure. Identified subjects are then examined extensively and followed‐up for at least 5 years to detect actual transition to psychosis.

Results:  Of 50 subjects who have been followed up for 1–5 years by now, 16 have progressed to frank psychosis, 12 of them during the first 12 months of follow‐up.

Conclusion:  At this stage, our approach seems to be promising for the early detection of psychosis. Further results from this ongoing study will hopefully permit us to optimize the assessment procedure.
A double‐blind, placebo‐controlled trial of sibutramine for clozapine‐associated weight gain
Authors: Henderson D. C. , Fan X. , Copeland P. M. , Borba C. P. , Daley T. B. , Nguyen D. D. , Zhang H. , Hayden D. , Freudenreich O. , Cather C. , Evins A. E. , Goff D. C.
Published: June 2006

Objective: This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine‐associated weight gain.

Method: This was a 12‐week double‐blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine‐treated schizophrenia or schizoaffective disorder subjects.

Results: Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels.

Conclusion: Sibutramine treatment did not show significant weight loss compared with placebo in clozapine‐treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow‐up duration is warranted.
Type 2 diabetes and periodontal indicators: epidemiology in France 2002–2003
Authors: Mattout C. , Bourgeois D. , Bouchard P.
Published: June 2006

Background and Objective:   Diabetes and periodontal disease have been associated in the literature. In the present study, the periodontal heath of noninsulin‐dependent diabetic adults was compared with that of a general population of nondiabetic patients.

Material and Methods:  In France, 2144 adults (age: 35–65 years) were examined for life habits (tobacco, alcohol), biological diagnosis (type II diabetes, arterial hypertension), biometry (weight, size) and biochemistry. Dental and periodontal data included plaque index, gingival index, probing depth, and clinical attachment loss.

Results:  Descriptive and multifactorial analysis evidenced a more severe periodontal disease in diabetic patients. Moreover, when the plaque index was held constant, the gingival index was more elevated in diabetics. In nondiabetics, age, gender, glycemia, alcohol, and tobacco smoking were identified as significant risk factors for periodontal disease. In contrast, in diabetic subjects, only tobacco smoking was a significant risk factor.

Conclusion:  In type II diabetics, the diabetes factor is probably more significant than periodontal risk factors, age, and gender.
Synergism between nifedipine and cyclosporine A on the incorporation of [35S]sulfate into human gingival fibroblast cultures in vitro
Authors: Flynn J. C. , Henderson J. S. , Johnson R. B.
Published: June 2006

Background and Objective:  We assessed the effects of cyclosporine A and nifedipine on the in vitro incorporation of [35S]sulfate into gingival fibroblast cell cultures derived from responder and nonresponder subjects who had received an organ transplant followed by a therapeutic regimen using a combination of those drugs.

Material and Methods:   Gingival fibroblasts were isolated from responder and nonresponder subjects and maintained in vitro. Prior to cell harvest, gingival interleukin‐1β concentrations were determined by enzyme‐linked immunosorbent assay (ELISA). Cells were untreated or exposed to either 10−7−10−10 m nifedipine or 100–500 ng/ml cyclosporine A. Incorporation of [3H]proline or [35S]sulfate into the cell cultures was determined by liquid scintillation analysis. In addition, the effects of 400 ng/ml cyclosporine A + 10−7 m nifedipine and 400 ng/ml cyclosporine A + 10−10 m nifedipine on incorporation of [35S]sulfate into the cell cultures was determined. Data were compared by factorial analysis of variance (anova) and a posthoc Tukey's test.

Results:   Gingiva from responders contained significantly more interleukin‐1β than gingiva from nonresponders (p < 0.01). The cell cultures derived from responders incorporated significantly more [35S]sulfate than those derived from nonresponders following exposure to either cyclosporine A or 10−7 m nifedipine. In addition, the exposure of fibroblasts derived from gingival overgrowth to either 400 ng/ml cyclosporine A + 10−7 m nifedipine or 400 ng/ml cyclosporine A + 10−10 m nifedipine significantly increased or decreased, respectively, the incorporation of [35S]sulfate into the cultures.

Conclusion:   The therapeutic combination of cyclosporine A and nifedipine could be a significant risk factor for gingival overgrowth in subjects susceptible to either agent. The mechanism for overgrowth could include edema secondary to increased sulfated‐glycosaminoglycan (sGAG) synthesis by fibroblasts, but further investigation is required.
An immunohistochemical study of the attachment mechanisms in different kinds of adhesive interfaces in teeth and alveolar bone of the rat
Authors: Arambawatta A. K. S. , Yamamoto T. , Wakita M.
Published: June 2006

Background and Objective:  This study was designed to examine the histological and immunohistochemical nature of different kinds of adhesive interfaces in the rat molar region under identical experimental conditions and to discuss the structural and functional similarities between these adhesive interfaces.

Material and Methods:  Four kinds of adhesive interfaces – an initial attachment layer for principal fibers on the developing alveolar bone surface, a reattachment layer for principal fibers on resorbed alveolar bone surface, cement lines on the alveolar bone surface unrelated to the principal fibers, and the cemento–dentinal junction – were examined in 25‐d‐old male Wistar rats. Routine histological staining, immunohistochemical staining for bone sialoprotein and osteopontin, and digestion tests with trypsin were conducted.

Results:  The adhesive interfaces showed very similar histological and immunohistochemical features: they were intensely hematoxylin‐stainable, deficient in collagen fibrils, and rich in bone sialoprotein and osteopontin. After trypsin treatment the four adhesive interfaces had lost immunoreactivity to bone sialoprotein and osteopontin, and the two adjacent tissue parts held together finally separated at the adhesive interfaces.

Conclusion:  The above findings suggest that (i) the different types of adhesive interfaces in the rat molar region have a common structure in that they are filled with highly accumulated bone sialoprotein and osteopontin and deficient in collagen fibrils; (ii) accumulated bone sialoprotein and osteopontin are closely associated with the adhesion at the interfaces; and (iii) the adhesive interfaces have a similar developmental process.
Periodontal healing may be affected by aging: a histologic study in rats
Authors: Benatti B. B. , Neto J. B. C. , Casati M. Z. , Sallum E. A. , Sallum A. W. , Nociti F. H.
Published: June 2006

Background and Objective:  Although wound healing has been reported to be impaired with aging, very little is known about its effect on periodontal tissues. Therefore, the aim of this study was to evaluate, histologically in rats, the influence of aging on a spontaneous periodontal healing model.

Material and Methods:  Twenty‐four male Wistar rats were used and assigned to the following groups: control (n = 12; 2 mo old) and aged (n = 12; 18 mo old). Fenestration defects (4 × 3 × 1 mm) were created bilaterally at the buccal aspect of the distal root of the first mandibular molars, and the mandibulae were retrieved 3 and 6 wk postoperatively. The percentage of bone fill and density of newly formed bone, new cementum formation (NC), and the extension of the remaining defect (ERD) were histometrically obtained.

Results:  Intragroup analysis demonstrated that, except for cementum, all histological parameters significantly improved over time (p < 0.05). Intergroup analysis additionally showed that the defects were initially similar in size, and that at 3 wk aging negatively influenced newly formed bone (86.38 ± 2.99% and 73.06 ± 3.21%, p < 0.001, for groups control and aged, respectively), BF (75.84 ± 16.53% and 57.70 ± 22.28%, p = 0.014) and ERD (0.41 ± 0.20 mm and 1.17 ± 0.37 mm, p < 0.001). At 6 wk, aging negatively influenced newly formed bone (88.12 ± 2.90% and 78.19 ± 5.35%, p < 0.001, for groups control and aged, respectively) and ERD (0.01 ± 0.006 mm and 0.34 ± 0.18 mm, p = 0.003), but not BF (98.15 ± 2.43% and 87.87 ± 11.63%, p > 0.05). No new cementum was formed along the root surface in the above groups.

Conclusion:  Within the limits of the present study, data analysis suggests that aging may impair, but not prevent, periodontal healing.
Regulation of epithelial cell growth factor receptor protein and gene expression using a rat periodontitis model
Authors: Ekuni D. , Firth J. D. , Putnins E. E.
Published: June 2006

Background and Objective:  Regulation of epithelial cell behavior associated with periodontitis is not well elucidated but many responses will ultimately be regulated by growth factor receptors. Using a rat experimental periodontitis model, protein and gene expression of select growth factor receptors in junctional and pocket epithelium were examined.

Material and Methods:  Periodontal disease was induced by daily topical application of lipopolysaccharide using an established protocol. Animals were killed at time 0 (control), and at 2 and 8 wk. Frozen tissue samples were collected from the right palatal gingival soft tissue, and the left periodontal tissues were decalcified and embedded in paraffin. Laser microdissection and quantitative reverse transcription–polymerase chain reaction (qRT–PCR) was used to quantify keratinocyte growth factor receptor (KGFR), hepatocyte growth factor receptor (HGFR), epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor 1 (FGFR1) gene expression, and in situ RT–PCR localized these increases to specific epithelial cells. Receptor protein expression was examined immunohistochemically. In cell culture, induction of HGFR and KGFR protein expression by serum, lipopolysaccharide and pro‐inflammatory cytokines were examined using flow cytometry.

Results:  Eight‐week tissue samples exhibited histological changes consistent with periodontitis. KGFR and HGFR gene and protein expression were significantly induced at the 8 wk time point. KGFR expression was significantly up‐regulated in basal and parabasal pocket epithelial cells, but HGFR was up‐regulated throughout the pocket epithelium. In cell culture serum, lipopolysaccharide and pro‐inflammatory cytokines, interleukin‐1β and tumour necrosis factor‐α significantly induced KGFR protein receptor expression, but HGFR expression was only induced by serum.

Conclusion:  KGFR and HGFR are highly up‐regulated in this model of periodontal disease and may play a significant role in regulating the proliferation and migration of pocket epithelium.
The βI/βIII‐tubulin isoforms and their complexes with antimitotic agents
Authors: Magnani Matteo , Ortuso Francesco , Soro Simonetta , Alcaro Stefano , Tramontano Anna , Botta Maurizio
Published: June 2006

Both microtubule destabilizer and stabilizer agents are important molecules in anticancer therapy. In particular, paclitaxel has been demonstrated to be effective for the treatment of ovarian, breast, and nonsmall cell lung carcinomas. It has been shown that emergence of resistance against this agent correlates with an increase in the relative abundance of tubulin isoform βIII and that the more recently discovered IDN5390 can be effectively used once resistance has emerged. In this paper, we analyze the binding modes of these antimitotic agents to type I and III isoforms of β‐tubulin by computational methods. Our results are able to provide a molecular explanation of the experimental data. Using the same protocol, we could also show that no preference for any of the two isoforms can be detected for epothilone A, a potentially very interesting drug for which no data about the emergence of resistance is currently available. Our analysis provides structural insights about the recognition mode and the stabilization mechanism of these antimitotic agents and provides useful suggestions for the design of more potent and selective antimitotic agents.
Helicobacter pylori infection induces accumulation of Vδ1 T cells via CCR2 upregulation
Authors: FUTAGAMI S. , HIRATSUKA T. , SHINDO T. , HAMAMOTO T. , UEKI N. , SUZUKI K. , KUSUNOKI M. , WADA K. , MIYAKE K. , OHASHI K. , GUDIS K. , TSUKUI T. , SAKAMOTO C.
Published: June 2006

Background

We investigated factors that impact γδ T‐cell phenotype accumulation in Helicobacter pylori‐infected gastric mucosa and peripheral blood.

Aim

To determine whether H. pylori infection induces accumulation of Vδ1 T cells via CC chemokine receptor 2 (CCR2) upregulation.

Methods

Mucosal biopsy samples from 22 H. pylori‐free and 75 H. pylori‐infected patients were classified into grades I–III gastritis groups as per our previous study. The number of γδ, Vδ1 and Vδ2 T cells was evaluated by immunostaining and then compared with counts in 17 patients after H. pylori eradication. TGF‐β, IFN‐γ and CCR2 mRNA expression levels in Vδ1 T cells stimulated by H. pylori component were also evaluated.

Results

γδ T‐cell count was significantly higher in grade III gastritis patients, who exhibited strong IgA and IgG responses to H. pylori urease, than in other groups. Vδ1 T cells were found dominantly residing in H. pylori‐infected gastric mucosa, whereas Vδ2 T cells were mainly found in peripheral blood. Vδ1 T‐cell count was significantly reduced after H. pylori eradication therapy. In in vitro studies, H. pylori component stimulation significantly upregulated both TGF‐β and IFN‐γ production in supernatant from stimulated Vδ1 T cells. Moreover, CCR2 mRNA expression in Vδ1 T cells stimulated with H. pylori components was significantly increased.

Conclusion

Accumulation of Vδ1 T cells may occur through the upregulation of CCR2 expression.
Comparison of efficacies of dual therapy and triple therapy using rabeprazole in second‐line eradication of Helicobacter pylori in Japan
Authors: KAWAI T. , KAWAKAMI K. , KATAOKA M. , TAIRA S. , ITOI T. , MORIYASU F. , TAKAGI Y. , AOKI T. , RIMBARA E. , NOGUCHI N. , SASATSU M.
Published: June 2006

Background

The only authorized second‐line Helicobacter pylori regimen in Japan is proton pump inhibitor + amoxycillin + clarithromycin. However, it has been reported that this second‐line regimen is not effective. In this study, we evaluated the efficacy of dual and triple eradication therapies using rabeprazole as second‐line H. pylori eradication regimens.

Aim

To evaluate the efficacy of dual and triple eradication therapies using rabeprazole as second‐line H. pylori eradication therapy.

Methods

Sixty‐two H. pylori‐positive patients with first‐line eradication failure were randomly assigned to two groups. The RAM group was administered rabeprazole 20 mg + amoxycillin 1500 mg + metronidazole 500 mg daily for 1 week. The RA group was administered rabeprazole 40 mg + amoxycillin 2000 mg daily for 2 weeks. Eradication of H. pylori infection was determined by 13C‐urea breath testing at 8 weeks after completion of treatment. Prior to treatment, amoxycillin, clarithromycin and metronidazole susceptibility, and CYP2C19 phenotype status were determined.

Results

Eradication rates for the RAM and RA groups were 97% and 74%, respectively. Eradication rates were not influenced by CYP2C19 phenotype in either group. Eradication rates for clarithromycin‐resistant patients were 100% in the RAM group and 77% in the RA group.

Conclusions

One week with RAM therapy and 2 weeks with RA therapy were effective as second‐line eradication therapy for H. pylori infection; moreover, RAM was more effective than RA therapy.
Review article: is there a common principle in the development of gastrointestinal cancers? Stem cells in the origin of cancer
Authors: WRIGHT N. A.
Published: June 2006

Background

Accumulating evidence, outlined in this review, at last provides some elucidation of the orgin of gastrointestinal epithelial tumours.

Methods

New techniques, such as following the process of crypt or gastric gland purification following mutation in genes encoded by the mitochondrial genome, have shown that mutations spead within the proliferative unit, either gastric gland or intestinal crypt, by clonal purification or monoclonal conversion. Spreading otside the crypt or gland then takes place by fission.

Results

Future research should focus on the mecanisim by which mutated stem cells colonize crypts, and on the mechanisms of crypt fission itself.
Efficacy of proton pump inhibitors for cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes
Authors: AMANO Y. , CHINUKI D. , YUKI T. , TAKAHASHI Y. , ISHIMURA N. , KAZUMORI H. , KUSHIYAMA Y. , KARIM RUMI M. A. , ISHIHARA S. , KINOSHITA Y.
Published: June 2006

Background

Controversy exists concerning the efficacy of acid suppressants in the regression of Barrett's oesophagus.

Aim

To evaluate the effect of proton pump inhibitors on cyclooxygenase‐2 expression, cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes.

Methods

Four hundred and sixty‐six biopsy samples of Barrett's oesophagus from 358 non‐treatment patients and 81 from 61 chronic proton pump inhibitor users were immunohistochemically examined using anti‐cyclooxygenase‐2 protein, anti‐proliferating cell nuclear antigen and anti‐single stranded DNA antigens in both mucin phenotypes of Barrett's oesophagus.

Results

Prevalence of the cyclooxygenase‐2 expression pattern did not significantly differ between the non‐treatment and proton pump inhibitor users. In those using proton pump inhibitors, significant suppression of the proliferating cell nuclear antigen index was found in Barrett's oesophagus with the gastric‐predominant mucin phenotype, but not with the intestinal‐predominant mucin phenotype. Apoptosis indices in chronic proton pump inhibitor users did not significantly differ between the two mucin phenotypes.

Conclusions

Proton pump inhibitors suppress cellular proliferation in Barrett's oesophagus with the gastric‐predominant mucin phenotype but not in that with the intestinal‐predominant mucin phenotype. This finding may at least partly explain the ongoing controversy surrounding the notion that all cases of Barrett's oesophagus respond to acid‐suppressive therapy.
Interactions between the grading of gastric atrophy associated with Helicobacter pylori infection and the severity of clinical symptoms and delay in gastric emptying in patients with functional dyspepsia
Authors: KADOUCHI K. , TOMINAGA K. , OCHI M. , KAWAMURA E. , SASAKI E. , SHIBA M. , WATANABE T. , FUJIWARA Y. , OSHITANI N. , HIGUCHI K. , SHIOMI S. , ARAKAWA T.
Published: June 2006

Background

Atrophic and inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia. However, detailed data regarding the correlation between the severity of these changes and the symptoms of functional dyspepsia are not available.

Aim

To evaluate grading scales of gastric atrophy and inflammation, severity of clinical symptoms, and gastric emptying in patients with functional dyspepsia.

Methods

Ninety‐three patients with dyspepsia were enrolled. The severity of gastric atrophy was graded through serological and histological examination, and gastric inflammation was evaluated histologically. Clinical symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale, including subscales for abdominal pain, acid reflux, diarrhoea, indigestion and constipation. Gastric emptying half‐time was measured using a radioisotope technique.

Results

Helicobacter pylori infection and gastric inflammation influenced neither clinical symptoms nor gastric emptying time. However, a correlation was observed between gastric atrophy as graded by serological examination and indigestion (R = 0.31, P = 0.01). Histological examination also showed a correlation between gastric atrophy and abdominal pain and indigestion (R = 0.31, P = 0.04 and R = 0.35, P = 0.02 respectively).

Conclusion

Gastric atrophy associated with H. pylori infection may be partly responsible for the clinical symptoms experienced by patients with functional dyspepsia.
Helicobacter pylori‐induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression
Authors: SHIOTANI A. , IISHI H. , UEDO N. , ISHIHARA R. , ISHIGURO S. , TATSUTA M. , NAKAE Y. , KUMAMOTO M. , HINOI T. , MERCHANT J. L.
Published: June 2006

Background

The loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia.

Aim

To examine CDX2 expression in the non‐cancerous mucosa of patients with gastric cancer and compared it to CDX2 expression in controls with intestinal metaplasia.

Methods

Sixty patients who had undergone endoscopic mucosal resection for early gastric cancer and 60 gender‐ and age‐matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated by immunostaining.

Results

Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7–18.9, P < 0.001). CDX2 negatively correlated with sonic hedgehog expression, however, multivariate analysis revealed that CDX2 correlated with the intestinal metaplasia scores. Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve was higher in the cancer group than in the controls. Sonic hedgehog indices in the corpus decreased and CDX2 indices in both areas increased in patients in the ascending order of those without intestinal metaplasia, those with complete intestinal metaplasia and those with incomplete intestinal metaplasia (P < 0.001).

Conclusions

Loss of sonic hedgehog expression and aberrant expression of CDX2 correlates with the type of intestinal metaplasia and may play a role in carcinogenesis.
Colonic mucosal lesions associated with long‐term administration of non‐steroidal anti‐inflammatory drugs
Authors: OHKUSA T. , TERAI T. , ABE S. , KOBAYASHI O. , BEPPU K. , SAKAMOTO N. , KUROSAWA A. , OSADA T. , HOJO M. , NAGAHARA A. , OGIHARA T. , SATO N.
Published: June 2006

Background

Effects of long‐term administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) on the colon have not been well characterized.

Aim

To investigate colonoscopic findings and prevalence of adverse events following long‐term use of NSAIDs.

Methods

The study included 425 patients (mean 66.4 years) treated for over one year with NSAIDs, and 2125 age‐ and sex‐matched patients without NSAIDs as controls. Eligible candidates were selected by medical record review for underlying diseases, pre‐endoscopic symptoms, category of NSAIDs used, and duration of use. We used endoscopy to study lesion characteristics.

Results

The occurrence rate of colonic lesions or bleeding in the NSAIDs user (13/425, 3.1%) was higher than that in controls (28/2125, 1.3%) (p = 0.017). Colitis was found in 10 of the 13 patients. The sigmoid colon, descending colon or both (70.0%) was commonly involved, and showed segmental ischemic colitis features in 8 of the 13 patients (61.5%). Among these, duration of use ranged from 1‐30 years (mean 7.8). Nine of 13 patients (69.2%) took low‐dose aspirin.

Conclusion

The prevalence of colonic lesions in long‐term NSAIDs users is much lower than that of upper gastrointestinal side effects, but higher than that of colonic lesions in non‐NSAIDs users. The most common features of NSAIDs‐associated colitis were segmental ischeznia.
Enhanced plasma ghrelin levels in patients with functional dyspepsia
Authors: NISHIZAWA T. , SUZUKI H. , NOMOTO Y. , MASAOKA T. , HOSODA H. , MORI M. , OHARA T. , MORISHITA T. , KANGAWA K. , HIBI T.
Published: June 2006

Background

Ghrelin, growth‐hormone‐releasing peptide, has been reported to accelerate food intake and gastrointestinal motility.

Aim

The present study was designed to investigate the plasma ghrelin levels in patients with functional dyspepsia (FD).

Patients and Methods

Ninety‐seven patients, who showed no evidence of peptic ulcer disease or gastrointestinal cancer on upper gastrointestinal endoscopy, were recruited. Seventeen patients who had no gastrointestinal symptoms were recruited as controls. Forty‐seven patients were diagnosed to be suffering from FD, based on the Rome II criteria. The FD patients were further subdivided into those with ulcer‐like FD, dysmotility‐like FD and non‐specific‐type FD, based on their Gastrointestinal Symptom Rating Scale (GSRS) scores. Fourteen patients were categorized as having gastro‐oesophageal reflux disease, and 19 patients were excluded as having the irritable bowel syndrome, based on the GSRS. The plasma ghrelin levels were measured by radioimmunoassay.

Results

The plasma ghrelin levels were significantly higher in FD patients, especially in those with dysmotility‐like FD, as compared with those in controls. The plasma ghrelin levels were also correlated well with the indigestion scores.

Conclusion

Plasma ghrelin levels are significantly higher in patients with dysmotility‐like FD, suggesting that this parameter could become useful as a novel supportive marker for the diagnosis of FD.
Evaluation of the role of Helicobacter pylori as a promoter of gastric cancer from the viewpoint of structural chromosomal aberration
Authors: OHARA T. , KASANUKI J. , MORISHITA T. , YAMAMOTO N. , SHIBAHARA T. , SUZUKI H. , MASAOKA T. , NISHIZAWA T. , HIBI T.
Published: June 2006

Aim

To examine whether Helicobacter pylori induces structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI) in the infected gastric mucosa.

Methods

Subjects were 13 patients with H. pylori‐positive and 9 with H. pylori‐negative gastric cancer and 20 patients with H. pylori‐positive and 4 patients with H. pylori‐negative chronic gastritis. Gastric mucosal tissues were endoscopically sampled from each subject. Each sample was checked for structural chromosomal aberrations (LOH and MSI) by PCR and microsatellite analysis, using a total of 31 primers corresponding to the regions containing the major genes of chromosomes 1q, 5q, 7q, 17p, 17q, 18q and 21q.

Results

All tissue samples obtained from cancer‐affected regions of the stomach had structural chromosomal aberrations (LOH or MSI), irrespective of H. pylori infection. The degree of structural chromosomal aberration was greater in poorly differentiated than well‐differentiated adenocarcinoma. In addition, structural chromosomal aberrations were also found in a few samples obtained from the chronic atrophic gastritis group, irrespective of H. pylori infection.

Conclusions

It seems unlikely that H. pylori serves as a direct promoter of gastric cancer, and H. pylori‐positive chronic gastritis may not always be a precancerous state.
Interaction between Helicobacter pylori and immune response to CagA: CagA antibody may down‐regulate bacterial colonization and tyrosine phosphorylation
Authors: DEGUCHI R. , WATANABE K. , KOGA Y. , KIJIMA H. , TAKAGI A.
Published: June 2006

Background

CagA+Helicobacter pylori strains are associated with the development of gastroduodenal diseases. H. pylori possess a type IV secretion system that is responsible for the translocation of CagA into host cells.

Aim

To investigate the correlation between the CagA status and the severity of histological gastritis and to analyse the tyrosine phosphorylation of CagA.

Methods

A total of 149 H. pylori status was determined via urine antibody to H. pylori, histological examination and serum antibody against CagA. Histological gastritis was evaluated using the updated Sydney system and scored from 0 to 3. Tyrosine phosphorylation was analysed using immunoprecipitation and immunoblotting.

Results

Anti‐CagA titres were correlated with the severity of mononuclear cell infiltration. In contrast, mean anti‐CagA in patients with grade 2 bacterial density was significantly higher than those with grade 0 (P < 0.01). Mean anti‐titre in patients with grade 3 tended to be lower than that seen with grade 2. CagA tyrosine phosphorylation was significantly more common in bacteria isolated from CagA‐antibody‐negative patients (93%;13/14) than from CagA‐antibody‐positive patients (29%; 4/14, P = 0.0007).

Conclusions

Host–bacteria interaction is regarded as one of the important factors in the development of gastroduodenal diseases.