bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombocytopenia in association with splenomegaly during granulocyte–colony‐stimulating factor treatment in mice is not caused by hypersplenism and is resolved spontaneously
Authors: Takamatsu Yasushi , Jimi Shiro , Sato Tomohito , Hara Shuuji , Suzumiya Junji , Tamura Kazuo
Published: December 2006

BACKGROUND: Granulocyte–colony‐stimulating factor (G‐CSF) is used for hematopoietic progenitor cell (HPC) mobilization. Platelet (PLT) counts decrease during G‐CSF administration. The mechanisms have not been determined, however. Because splenic pooling of PLTs caused thrombocytopenia in patients with splenomegaly and splenic enlargement was observed in G‐CSF–treated donors, it was hypothesized that hypersplenism might cause G‐CSF–induced thrombocytopenia.

STUDY DESIGN AND METHODS: Mice were treated with several concentrations of G‐CSF, and PLT count was measured. Because transfused PLTs should be cleared rapidly from the blood stream under hypersplenic state, PLT life span was studied. To determine direct role of spleen on thrombocytopenia, G‐CSF was given to splenectomized mice. Because PLT count did not decrease in G‐CSF–expressing transgenic mice, G‐CSF was given to mice for a longer period of time and PLT count was investigated.

RESULTS: PLT counts decreased while spleen weight increased in a dose‐dependent manner by G‐CSF treatment. No significant difference in PLT life span was found between G‐CSF–treated and control mice. Histologic analysis showed no significant increase in PLT numbers trapped in either spleen or other tissue after PLT transfusion in G‐CSF–treated mice. In splenectomized mice as well as in normal mice, G‐CSF caused thrombocytopenia. When G‐CSF was given to mice for a longer period of time, PLT counts decreased during the first 7 days and thereafter began to increase followed by returning to baseline on Day 15.

CONCLUSION: Thrombocytopenia coincided with splenomegaly during G‐CSF treatment, but hypersplenism was not responsible for thrombocytopenia. G‐CSF–induced thrombocytopenia was a transient event and improved spontaneously despite continual G‐CSF treatment.
Platelet function in whole‐blood donors is impaired: the effects of painkillers
Authors: Curvers Joyce , Dielis Arne W.J.H. , Heeremans Judith , Van Wersch Jan W.J.
Published: December 2006

BACKGROUND: Aspirin (ASA) or non–aspirin‐like nonsteroidal anti‐inflammatory drugs (NSAIDs) influence platelet (PLT) function by inhibiting cyclooxygenase enzymes. In this study, the aim was to address the use of ASA or NSAIDs before donation and the effect on PLT function.

STUDY DESIGN AND METHODS: Donors were asked questions about recent use of ASA or NSAIDs. Furthermore, PLT function was evaluated by measurement of the closure time (CT) in a PLT function analyzer (PFA‐100, Dade Behring) and by aggregometry (response to ADP or arachidonic acid [AA]).

RESULTS: Of 100 questioned donors, 22 percent had used ASA (n = 4), NSAIDs (n = 6), or paracetamol (n = 12) before donation. Upon assessment of the PLT function in the PFA‐100, 27 donors showed values of greater than 180 seconds, indicative of impaired PLT function. Of these, only 7 had used pain killers before donation. Furthermore, 15 of 22 users had normal CTs. Aggregation after stimulation with AA was absent in 33 PLT‐rich samples. Again only 8 had reported use of ASA (3), NSAIDs (1), or paracetamol (4). Of the 22 users, 14 had normal AA aggregation responses. All donor samples showed ADP‐induced aggregation, indicating PLT integrity. There was no difference between the group of donors who reported the intake of ASA or NSAIDs and the group of donors who did not with respect to the tested PLT function assays.

CONCLUSION: It is concluded that there is a considerable group of donors that use PLT‐influencing medication before donation. A relation between the reported use and impaired PLT function in blood donors could not be established, however. Impaired PLT function as tested may have other causes than intake of ASA or NSAIDs.
Evaluation of a new enzyme‐linked immunosorbent assay for detection of Chagas antibody in US blood donors
Authors: Tobler Leslie H. , Contestable Paul , Pitina Lubor , Groth Holly , Shaffer Shirley , Blackburn Gary R. , Warren Harold , Lee Stephen R. , Busch Michael P.
Published: December 2006

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, represents a serious blood safety problem due to increasing immigration from Latin America. The Food and Drug Administration recently recommended implementation of Chagas antibody screening for US donors as soon as a suitable assay is licensed. An anonymized preclinical study of a prototype T. cruzi lysate‐based enzyme‐linked immunosorbent assay (ELISA) developed by Ortho‐Clinical Diagnostics was conducted.

STUDY DESIGN AND METHODS: Two populations of specimens were evaluated: 1) 10,192 sequential donations from blood donors residing in the El Paso, Texas, area and 2) 178 specimens from South America which were presumptively positive for antibodies to T. cruzi and purchased from commercial vendors.

RESULTS: A total of 10,189 (99.97%) of the 10,192 screened donor specimens did not react, whereas 3 (0.03%) tested initially reactive. The 3 initially reactive specimens tested repeat reactive and were confirmed by radioimmunoprecipitation analysis (RIPA). Based on antibody profile analysis, 2 of the 3 Chagas‐positive specimens were from the same donor. Observed specificity of the test was therefore 100 percent. Of the specimens from South America, 173 of 178 were reactive by the prototype ELISA. Of the 5 nonreactive specimens, all did not react by indirect fluorescence assay, but 4 were positive by RIPA. Therefore, calculated sensitivity of the ELISA was 97.7 percent (173/177).

CONCLUSIONS: These studies indicate that the prototype ELISA has excellent sensitivity and specificity for detection of antibodies to T. cruzi in donors. Moreover, among donations from a geographically selected collection region of the United States, observed seroprevalence was 0.03 percent.
Predictors of response and relapse in a cohort of adults with thrombotic thrombocytopenic purpura‐hemolytic uremic syndrome: a single‐institution experience
Authors: Tuncer Hande H. , Oster Robert A. , Huang Shu T. , Marques Marisa B.
Published: December 2006

BACKGROUND: Thrombotic thrombocytopenic purpura‐hemolytic uremic syndrome (TTP‐HUS) is a diagnosis of exclusion when a patient presents with the sine qua non findings of thrombocytopenia and microangiopathic hemolytic anemia without an identifiable cause. Although most patients respond to therapeutic plasma exchange (TPE), a significant number of patients relapse. The aim was to determine if clinical, laboratory, and/or treatment features could predict response and/or relapse.

STUDY DESIGN AND METHODS: This study was a retrospective review of adults with TTP‐HUS treated with TPE at our institution from January 1996 to February 2004.

RESULTS: The study population consisted of 90 patients (69% female) with mean age of 45 years and mostly obese (65%). The majority of cases were considered idiopathic. Ten patients died (11%) from the disease before achieving a response, whereas 79 percent were considered responders. Obesity and severe anemia at presentation were predictors of response to TPE (p = 0.0126 and p = 0.0071, respectively). Among the responders, 28 percent relapsed in a median of 14 months. Male sex, severe thrombocytopenia (mean ± SD, 13 × 109 ± 8 × 109/L), and higher lactate dehydrogenase pre‐/posttreatment ratio were associated with relapse (p values of 0.0141, 0.0199, and 0.0407, respectively). ADAMTS‐13 values were not obtained on enough number of patients to provide important data.

CONCLUSION: Although patient and laboratory characteristics associated with response and relapse were identified, there was significant overlap between patient groups. Thus, our findings offer preliminary evidence and do not yet justify short‐ or long‐term changes in the management of patients with TTP‐HUS.
Evaluation of platelet activation and cytokine release during storage of platelet concentrates processed from buffy coats either manually or by the automated OrbiSac system
Authors: Vetlesen Annette , Mirlashari Mohammad Reza , Ezligini Farshid , Kjeldsen‐Kragh Jens
Published: December 2006

BACKGROUND: This study aimed to compare platelet (PLT) quality during storage of buffy coat (BC) PLT concentrates (PCs), prepared either manually or by the automated OrbiSac system (Gambro BCT).

STUDY DESIGN AND METHODS: Following overnight storage at 20 to 22°C, five BCs were pooled with 300 mL of PLT additive solution. Twenty‐one PCs were produced manually (M‐PCs) and 21 by the automated OrbiSac system (A‐PCs). Swirling, PLT count, mean PLT volume, blood gas analyses, potassium, glucose, and lactate were assessed. Expression of the activation markers CD42a, CD62P, and PAC‐1 was analyzed by flow cytometry on resting PLTs and PLTs stimulated with thrombin receptor agonist peptide (TRAP). Levels of CCL5 and transforming growth factor‐β1 (TGF‐β1) were measured by enzyme‐linked immunosorbent assay.

RESULTS: The A‐PCs had significantly larger volume and higher PLT yield, PLT recovery, and white blood cell concentration than the M‐PCs, whereas the red blood cell content was significantly highest in the M‐PCs. pH levels were between 6.9 and 7.2 in all PCs. Neither glucose consumption nor lactate production differed significantly over time. A‐PCs had, compared to M‐PCs, significantly higher expression of CD62P on resting PLTs, lower capacity for up regulating CD62P on TRAP‐stimulated PLTs, and higher levels of CCL5 during storage. TRAP‐stimulated A‐PCs had a significantly higher potential for down regulation of CD42a than M‐PCs. No difference was found in TGF‐β1 levels or TRAP‐induced up regulation of PAC‐1.

CONCLUSION: The levels of CCL5 and the expression of CD62P in resting and stimulated PLTs indicate that PLTs in A‐PCs are slightly more activated than in M‐PCs, but the clinical importance of this finding is yet unknown.
Assessment of education and computerized decision support interventions for improving transfusion practice
Authors: Rothschild Jeffrey M. , McGurk Siobhan , Honour Melissa , Lu Linh , McClendon Aubre A. , Srivastava Priya , Churchill W. Hallowell , Kaufman Richard M. , Avorn Jerry , Cook E. Francis , Bates David W.
Published: December 2006

BACKGROUND: Overuse of blood products is common, but prior efforts to improve transfusion decisions have met with limited success.

STUDY DESIGN AND METHODS: This study examines transfusion practices before and after a conventional educational intervention followed by a randomized controlled trial of a decision support (DS) intervention with computerized physician order entry (CPOE) for red blood cell, platelet, and fresh‐frozen plasma orders. The study was conducted in an academic medical center between April 2003 and June 2004. Orders originating from units not using CPOE with DS (e.g., the emergency department) were excluded. Junior housestaff were randomly assigned into a control group and an intervention group who received DS for transfusion orders. Transfusion orders were initially classified according to guideline rules as DS‐agree or DS‐disagree. Chart reviews assessed inappropriateness for all DS‐disagree orders and a sample of DS‐agree orders. The total of inappropriate transfusion orders included chart review confirmed DS‐disagree orders and DS‐agree orders reclassified as inappropriate.

RESULTS: The percentages of inappropriate nonemergent transfusion orders during the baseline phase for the entire staff and randomly assigned junior housestaff were 72.6 percent (2154/2967) and 71.9 percent (1259/1752) and improved after conventional education to 63.8 percent (1699/2663; p < 0.0001) and 63.3 percent (1263/1996; p < 0.0001), respectively. The percentage of inappropriate orders in the DS intervention group continued to improve (59.6%, 804/1350; p < 0.0001). Physicians accepted 14 percent (133/939) of new DS‐recommended orders, especially recommendations to increase transfusion doses (73%).

CONCLUSIONS: Education and computerized DS both decreased the percentage of inappropriate transfusions, although the residual amount of inappropriate transfusions remained high.
Inactivation of Orientia tsutsugamushi in red blood cells, plasma, and platelets with riboflavin and light, as demonstrated in an animal model
Authors: Rentas Francisco , Harman Ronald , Gomez Charlotte , Salata Jeanne , Childs Joseph , Silva Tonya , Lippert Lloyd , Montgomery Joshua , Richards Allen , Chan Chye , Jiang Ju , Reddy Heather , Li John , Goodrich Raymond
Published: December 2006

BACKGROUND: Treatment of blood products with riboflavin and light has been used to reduce the number of certain pathogens. Orientia (formerly Rickettsia) tsutsugamushi, the scrub typhus agent, is an obligate intracellular bacterium that grows free in the cytoplasm of infected cells. This study evaluated the capability of riboflavin and light to inactivate O. tsutsugamushi in red blood cells (RBCs), platelets (PLTs), and plasma, as measured by mouse infectivity.

STUDY DESIGN AND METHODS: A total of 108 mice, equally divided into groups receiving RBCs, plasma, and PLTs, received untreated products infected with 100 to 105 organisms. Eighteen mice received products infected with 105 organisms and were subsequently treated with riboflavin and light. Mice were monitored daily for up to 17 days for signs and symptoms of infection (e.g., lethargy, labored breathing, rough coat) and killed upon appearance of symptoms or on Day 17 after infection. Real‐time polymerase chain reaction (PCR) on blood and Giemsa stains from peritoneal exudates were performed.

RESULTS: A total of 102 of 108 mice receiving the untreated products developed signs and symptoms of infection and had positive PCR and Giemsa stain results. None of the 18 animals receiving riboflavin and light–treated blood products exhibited signs or symptoms of infection, nor was infection observed by PCR testing or Giemsa staining.

CONCLUSIONS: Riboflavin and light are effective in reducing O. tsutsugamushi. Mice injected with blood products inoculated with 105 organisms and treated with riboflavin and light did not experience any signs or symptoms of infection, 17 days after inoculation. A 5‐log reduction of this organism in blood was achieved as assayed in an animal model.
Advances in the Approaches to Ablation of Complex Arrhythmias
Authors: THORNTON A. S. , JORDAENS L. J.
Published: December 2006

A complex arrhythmia is one where successful ablation represents a serious challenge to the treating physician, and in this situation an advanced solution such as the combination of imaging with mapping and the ability to deliver a newer energy form using remote navigation may be a combined option some may wish was presently available. As will be discussed, there have been many advancements in the armamentarium of the electrophysiologist, and the above scenario may not be too far removed. This is not an exhaustive review, but serves to highlight some of the issues. Hopefully some, if not all, of the advances discussed will assist us in improving success rates, while decreasing risks and complications. The ability to allow less experienced and busy electrophysiology centers to perform complex ablation with similar success and risk as more experienced labs may also be a possibility.
Remote Navigation and Ablation of Atrial Fibrillation
Authors: PAPPONE CARLO , SANTINELLI VINCENZO
Published: December 2006

We have developed a new approach based on remote navigation and ablation by a magnetic catheter in a large number of patients with paroxysmal, persistent, or permanent atrial fibrillation. The operator sits in a separate control room, away from the X‐ray beam and the patient's body. A 4 mm magnetic catheter is integrated with a newly developed electroanatomical mapping system. The catheter is moved by a joystick that allows to and fro movement inside the left atrium. Magnetic field vectors for each navigation target are stored and, if necessary, they are reapplied at any time while the magnetic catheter is navigated automatically. Remote circumferential pulmonary vein ablation is performed with a target temperature of 65°C and a power limit of 50 W. Navigation and ablation targets can be safely and successfully achieved in all patients in a relatively short period of time (usually in less than one hour). The manual approach is totally operator‐dependent, while the remote one is not, but it mostly depends on a well‐trained team. When combined with an accurate electroanatomical mapping system this remote technology allows not only to optimize contact and stability with tissue, but also to enable movement between preassigned intracardiac points automatically, either avoiding intervening tissue structures or moving at a defined rate across the surface of the intervening tissue. Finally, there is a significant shortening of radiation exposure time, relevant both for the unprotected patient and the operator.
Challenges and Solutions for Difficult Implantations of CRT Devices: The Role of New Technology and Techniques
Authors: SHEPARD RICHARD K. , ELLENBOGEN KENNETH A.
Published: December 2006

Introduction: Cardiac resynchronization therapy (CRT) can markedly improve heart failure treatment in selected patients, but left ventricular (LV) lead implantation can be difficult or optimal lead position not obtainable.

Methods: This review examines newer techniques and technologies to optimize implant success. Goals of implant include placement of the LV lead in a coronary vein near the midlateral left ventricle with good lead stability, adequate thresholds, and no phrenic nerve stimulation. We will examine methods to access difficult and tortuous veins, test multiple veins for the best pacing site, and avoid complications. Newer technologies that will be discussed include magnetic wire navigation using Stereotaxis™, endoscopic, and CT‐guided approaches, and nontraditional methods such as pericardial puncture for epicardial LV lead placement.

Conclusion: The methods discussed here may help to make CRT implant safer, faster, and more successful.
A Two‐Pronged Approach to Promote Food Science in U.S. High Schools
Authors: McEntire Jennifer Cleveland , Rollins Mary
Published: December 2006

ABSTRACT:  The Institute of Food Technologists (IFT), the IFT Foundation, and Discovery Education partnered to create and distribute food science information to science department and school counselor chairs in all 18000 U.S. high schools in January 2006. Two multimedia “kits” were generated for teachers and counselors, each consisting of DVDs with food science technical or career information, respectively, and a call to action to visit a newly created web microsite. To support and promote the program, IFT initiated a “Food Science Ambassador” program, where IFT member food scientists complete a brief survey indicating their interest in speaking with or visiting teachers, students, and counselors to discuss the field of food science or give a demonstration. IFT, through the career guidance committee, exhibited and conducted workshops at the National Science Teachers Association regional and national conferences, and coordinated a “Train the Trainer” program at the IFT Annual Meeting in Florida for local area science teachers and Food Science Ambassadors. Survey results from kit recipients were overwhelmingly positive, with over 97% of the respondents indicating that they intend to use the materials. The microsite developed for this program received over 18000 unique visits in the first 6 mo, and traffic to the IFT Teacher Resources web page increased. In the first 6 mo of its availability, nearly 250 IFT members have signed up to be Food Science Ambassadors. Long‐term metrics for success are in place and continue to be monitored.
Fostering an Interest in Science in a Typically Underrepresented Population
Authors: Davis Sarah F. , McEntire Jennifer Cleveland , Sarakatsannis James
Published: December 2006

ABSTRACT:  This “case study” details how food science was introduced into the classrooms of a typically underrepresented population. James Sarakatsannis, an 8th grade physical science teacher, was planning a unit that would use fast food to teach science to his classes, when he came across the Institute of Food Technologists (IFT) website and a wealth of information available to teachers. Along with the valuable materials James found on the website to teach food science, he also found the “Find a Food Scientist” tool and invited 3 local food scientists into his classroom at John Philip Sousa Middle School in the inner city of Washington, D.C., where many of his students represent a typically underrepresented population in the field of food science. Food was a common medium that all of his students were familiar with and had an interest in, and it turned out to be a great tool to discuss various physical science topics in the classroom. The local food scientist visits were an excellent supplement to the topics he was already covering with the students in class. Many students developed a greater interest in science in general after the unit on food science. The unit also may have planted the seed for an education or career in food science somewhere down the line for the 70 13‐ to 16‐year‐old students in James's 2 8th grade physical science classes.
Corneal flap thickness with the Moria M2 single‐use head 90 microkeratome
Authors: Huhtala Anne , Pietilä Juhani , Mäkinen Petri , Suominen Sakari , Seppänen Matti , Uusitalo Hannu
Published: December 2006

Purpose:  To analyse the accuracy of corneal flap thickness created in laser‐assisted in situ keratomileusis (LASIK) using the Moria Model 2 (M2) single‐use head 90 microkeratome.

Methods:  The corneal thickness of 300 (266 myopic and 34 hyperopic) eyes of 150 patients was measured by ultrasonic pachymetry preoperationally and intraoperationally after flap cut. The Moria M2 single‐use head 90, intended to create a flap with a thickness of 120 µm, was used in all eyes. The right eye was always operated first and the left eye second, using the same blade.

Results:  Mean corneal flap thickness was 115.4 µm (standard deviation [SD] 12.5) in the two eyes, 115.7 µm (SD 12.4, range 73–147 µm) in right eyes and 115.1 µm (SD 12.6, range 74–144 µm) in left eyes. Mean horizontal flap diameter was 9.1 mm (SD 0.2) and mean hinge length 4.1 mm (SD 0.1). There were no free flaps, incomplete flaps or flaps with buttonholes in the study. Occasional iron particles were observed in three (1.0%) eyes.

Conclusions:  As with most microkeratomes, the single‐use head 90 microkeratome cut thinner flaps than were intended. The range of the cuts was relatively wide. However, thin flaps did not increase the rate of flap‐related complications. The difference between the first and second eyes was not significant.
Stroma remodelling during healing of corneal surface irregularities induced by PTK
Authors: Panagiotopoulos Marios , Gan Lisha , Fagerholm Per
Published: December 2006

Purpose:  To study the histopathology of the remodelling process in the stroma after excimer‐laser‐induced corneal irregular injuries.

Methods:  Seven New Zealand white rabbits received in one eye a transepithelial plano photoablation (60 µm) and an additional plano ablation (25 µm). On the denuded stroma, an electron microscopy specimen grid was placed and another 25 µm ablation was applied to produce surface irregularities. Dichlorotriazinyl aminofluorescein (DTAF) was then applied for 45 seconds. Another seven right eyes of seven rabbits were ablated the same way but without using the grid, resulting in a plano ablation. All the rabbits were killed at weekly intervals after treatment. The harvested corneas from both eyes were further processed for haematoxylin‐eosin staining and were also stained with monoclonal antibodies directed against Ki‐67 antigen and α‐smooth muscle actin (α‐SMA). All specimens were examined under light and fluorescence microscope.

Results:  The corneal wounds were covered by epithelium during the first week. The 25 µm × 25 µm × 25 µm stromal irregularities were clearly discernible up to 3 weeks after treatment, during which time they melted and disappeared. A homogeneous zone was formed in which stroma cells laid down an initially disorganized stroma. This was sharply visible under a fluorescence microscope as a dark area between the dichlorotriazinyl aminofluorescein (DTAF) fluorescent stroma and autofluorescent epithelium. Very little response was seen in the plano‐ablated wound microscopically and in terms of positive stained cells.

Conclusion:  As the irregularities are flattened and the homogenous zone becomes repopulated with keratocytes forming extracellular matrix material (ECM), the cornea regains its previous architecture in both groups. The irregular wound surface promotes wound‐healing reactivity, a process that allows the cornea to compensate for the irregularities and heal to a functional state.
Temperament and response to the Trier Social Stress Test
Authors: Tyrka A. R. , Wier L. M. , Anderson G. M. , Wilkinson C. W. , Price L. H. , Carpenter L. L.
Published: December 2006

Objective:  The personality characteristics behavioural inhibition and neuroticism have been associated with mood and anxiety disorders and, in some studies, hypothalamic–pituitary–adrenal (HPA) axis hyperactivity. We recently reported that low levels of Novelty Seeking were associated with elevated plasma cortisol responses to the dexamethasone/corticotropin‐releasing hormone (Dex/CRH) test in healthy adults with no psychiatric disorder. The present study tested the association between temperament and HPA axis function in the same group of subjects using a standardized psychosocial neuroendocrine stress test.

Method:  Subjects completed diagnostic interviews, questionnaires, and the Trier Social Stress Test (TSST).

Results:  Novelty Seeking was inversely associated with plasma cortisol concentrations at baseline and throughout the TSST, but was not related to adrenocorticotropic hormone (ACTH) levels.

Conclusion:  Results of this study extend our previous finding in the Dex/CRH test to a psychosocial stress test. Future investigations are needed to replicate these findings and further elucidate how temperament and personality are linked to HPA function.
Decreased cerebral blood flow of thalamus in PTSD patients as a strategy to reduce re‐experience symptoms
Authors: Kim S. J. , Lyoo I. K. , Lee Y. S. , Kim J. , Sim M. E. , Bae S. J. , Kim H. J. , Lee J.‐Y. , Jeong D.‐U.
Published: December 2006

Objective:  To investigate alterations of regional cerebral blood flow (rCBF) in subjects with post‐traumatic stress disorder (PTSD).

Method:  Using [99Tcm]‐hexamethyl propylenamino oxime single photon emission computed tomography, the rCBF under resting condition was compared between 19 survivors of the Taegu subway fire with PTSD and 19 comparison subjects.

Results:  PTSD patients showed a decreased rCBF in the right thalamus and an increased rCBF in the right superior parietal lobe relative to comparison subjects (corrected P < 0.05). The rCBF in the right thalamus positively correlated with the severity of current re‐experience symptoms in PTSD subjects.

Conclusion:  Our finding of the thalamic rCBF decrease in PTSD patients may be a strategy to reduce re‐experience symptom, by evading the process of external and internal information which can evoke traumatic memory. In addition, the parietal rCBF increase in our PTSD patients might be related to altered information processing in PTSD.
Comparison of naturally occurring and ligature‐induced peri‐implantitis bone defects in humans and dogs
Authors: Schwarz Frank , Herten Monika , Sager Martin , Bieling Katrin , Sculean Anton , Becker Jürgen
Published: December 2006

Objectives: The aim of the present study was to evaluate and compare naturally occuring and ligature‐induced peri‐implantitis bone defects in humans and dogs.

Material and Methods: Twenty‐four partially and fully edentulous patients undergoing peri‐implant bone augmentation procedures due to advanced peri‐implant infections were included in this study (n=40 implants). Furthermore, peri‐implantitis was induced by ligature placement and plaque accumulation in five beagle dogs for three months following implant insertion (n=15 implants). The ligatures were removed when about 30% of the initial bone was lost. During open flap surgery, configuration and defect characteristics of the peri‐implant bone loss were recorded in both humans and dogs.

Results: Open flap surgery generally revealed two different classes of peri‐implant bone defects. While Class I defects featured well‐defined intrabony components, Class II defects were characterized by consistent horizontal bone loss. The allocation of intrabony components of Class I defects regarding the implant body allowed a subdivision of five different configurations (Classes Ia–e). In particular, human defects were most frequently Class Ie (55.3%), followed by Ib (15.8%), Ic (13.3%), Id (10.2%), and Ia (5.4%). Similarly, bone defects in dogs were also most frequently Class Ie (86.6%), while merely two out of 15 defects were Classes Ia and Ic (6.7%, respectively).

Conclusions: Within the limits of the present study, it might be concluded that configurations and sizes of ligature‐induced peri‐implantitis bone defects in dogs seemed to resemble naturally occurring lesions in humans.
Tactile sensibility of single‐tooth implants and natural teeth
Authors: Enkling Norbert , Nicolay Claudia , Utz Karl‐Heinz , Jöhren Peter , Wahl Gerhard , Mericske‐Stern Regina
Published: December 2006

Aim: The purpose of this randomized split‐mouth clinical trial was to determine the active tactile sensibility between singe‐tooth implants and opposing natural teeth and to compare it with the tactile sensibility of pairs of natural teeth on the contralateral side in the same mouth (intraindividual comparison).

Material and Methods: The hypothesis was that the active tactile sensibilities of the implant side and control side are equivalent. Sixty two subjects (n=36 from Bonn, n=26 from Bern) with single‐tooth implants (22 anterior and 40 posterior dental implants) were asked to bite on narrow copper foil strips varying in thickness (5–200 μm) and to decide whether or not they were able to identify a foreign body between their teeth. Active tactile sensibility was defined as the 50% threshold of correct answers estimated by means of the Weibull distribution.

Results: The results obtained for the interocclusal perception sensibility differed between subjects far more than they differed between natural teeth and implants in the same individual [implant/natural tooth: 16.7±11.3 μm (0.6–53.1 μm); natural tooth/natural tooth: 14.3±10.6 μm (0.5–68.2 μm)]. The intraindividual differences only amounted to a mean value of 2.4±9.4 μm (−15.1 to 27.5 μm). The result of our statistical calculations showed that the active tactile sensibility of single‐tooth implants, both in the anterior and posterior region of the mouth, in combination with a natural opposing tooth is similar to that of pairs of opposing natural teeth (double t‐test, equivalence margin: ±8 μm, P<0.001, power >80%). Hence, the implants could be integrated in the stomatognathic control circuit.
Subgingival plaque microbiota in HIV positive patients
Authors: Aas J. A. , Barbuto S. M. , Alpagot T. , Olsen I. , Dewhirst F. E. , Paster B. J.
Published: December 2006

Aim: To describe and compare the predominant bacterial and fungal species associated with gingivitis, periodontitis, and linear gingival erythema (LGE), in HIV positive subjects with different immune status.

Methods: Viral loads and CD4 levels determined HIV disease status. From pooled subgingival plaque, 16S and 18S rDNA were cloned and sequenced to determine species identity.

Results: One hundred and nine bacterial species were identified from 14 subjects. Nearly half of the species were not cultivable. Notably, the classical putative periodontal pathogens, Treponema denticola, Porphyromonas gingivalis and Tannerella forsythia were below the limit of detection and were not detected. Species of Gemella, Dialister, Streptococcus and Veillonella were predominant. In one HIV positive subject with periodontitis and low viral load, Gemella morbillorum, a known opportunistic pathogen, constituted 84% of the clones. Saccharomyces cerevisiae was the only fungal species detected in an LGE subject and in periodontitis subjects with high viral loads. In periodontitis patients with low viral loads, Candida albicans was predominant, while S. cerevisiae was only a minor component.

Conclusion: These case studies suggest that other bacterial species, rather than the classical periodontal pathogens, may be involved in periodontal diseases of subjects with HIV. These data are indicative of opportunistic infections in a highly susceptible immunocompromised host.
Microbiological outcomes of quadrant versus full‐mouth root planing as monitored by real‐time PCR
Authors: Jervøe‐Storm P.‐M. , AlAhdab H. , Semaan E. , Fimmers R. , Jepsen S.
Published: December 2006

Objectives: To study the short‐term microbiological changes following full‐mouth compared with quadrant wise scaling and root planing (FMRP and QRP) as well as long‐term effects.

Method: Twenty patients with chronic periodontitis were randomized into a test group treated in two sessions with subgingival scaling and root planing within 24 h (FMRP) and a control group treated quadrant by quadrant in four sessions at intervals of one week (QRP). Microbiological samples were taken in the two deepest pockets of the maxillary right quadrant immediately before treatment and after 1 day, 1, 2, 4, 8, 12, and 24 weeks. The samples were evaluated by real‐time PCR for quantification of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum ssp., Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia as well as for total bacterial counts (TBC).

Results: Treatment resulted in a TBC median log reduction of 0.75 (FMRP) and 0.72 (QRP). There were no differences between groups either for the short term (1 day–4 weeks) (analysis of variance: p=0.3150) or for long term (4–24 weeks) (analysis of variance: p=0.9671). Likewise, no differences were detected for selected target bacteria.

Conclusion: The results of the present study showed similar microbiological outcomes following both treatment modalities.
Women with a recent history of early‐onset pre‐eclampsia have a worse periodontal condition
Authors: Kunnen Alina , Blaauw Judith , Van Doormaal Jasper J. , Van Pampus Maria G. , Van Der Schans Cees P. , Aarnoudse Jan G. , Van Winkelhoff Arie J. , Abbas Frank
Published: December 2006

Objective: Pre‐eclampsia is a complication of pregnancy characterized by systemic vascular dysfunction and pathological changes in placental arteries. Growing evidence of chronic infection as an aetiological factor in vascular diseases prompted us to study maternal periodontal disease in subjects with early‐onset pre‐eclampsia (<34 weeks).

Methods: A case–control study was carried out on 17 early‐onset pre‐eclamptic women and 35 controls with uncomplicated pregnancies in a period of 3–28 months postpartum. All were Caucasians. Full‐mouth periodontal examinations were performed to determine the periodontal condition. Subgingival‐plaque samples were analysed by anaerobic culture techniques for the presence of seven bacterial periodontal pathogens. Potential confounders as age, smoking, educational level and body mass index were determined.

Results: Severe periodontal disease was found in 82% of the pre‐eclamptic and in 37% of the control group (p=0.009). After adjusting for age, smoking and educational level, the odds ratio was 7.9 (95% CI: 1.9–32.8). The periodontopathic microorganism Micromonas micros was more prevalent in the case group (p=0.040) while Campylobacter rectus was more prevalent in the control group (p=0.047).

Conclusion: These results indicate that Caucasian women with a recent history of early‐onset pre‐eclampsia have a worse periodontal condition, as compared with women with uncomplicated deliveries.
Preclinical development of hybrid cell vaccines for multiple myeloma
Authors: Walewska Renata , Teobald Iryna , Dunnion Debbie , Abdulmajed Hind , Aldred Micheala , Sadler Jean , Chapman Claire , Browning Michael
Published: December 2006

Immunotherapy may provide alternative or supplementary treatment of multiple myeloma (MM). We propose that hybrid cells, formed by fusing professional antigen‐presenting cells with malignant plasma cells, would induce immune responses capable of mediating tumour regression. The human B‐lymphoblastoid cell line, HMy2, was fused in vitro with CD138+ bead‐separated myeloma plasma cells from five patients with MM. The hybrid cell lines generated in these studies grew stably in tissue culture, and maintained their phenotypic and functional characteristics, providing self‐renewing cell lines with potential for therapeutic vaccination. The hybrid cells stimulated allogeneic and autologous T‐cell proliferative responses in vitro to a considerably greater degree than their respective parent myeloma plasma cells, and directly activated both CD4+ and CD8+ T‐cell responses. The enhanced T‐cell stimulation correlated with expression of CD80 on the hybrid cells, and was inhibited by CTLA4‐Ig fusion protein. The hybrid cell lines expressed several tumour‐associated antigens known to be expressed in myeloma. These data show that self‐replicating cell lines with enhanced immunostimulatory properties and potential for therapeutic vaccination can be generated by in vitro fusion of ex vivo myeloma cells and B‐lymphoblastoid cell lines.
Lack of effect of antenatal glucocorticoid therapy in the fetal baboon on cerebral cortical glucose transporter proteins
Authors: Antonow‐Schlorke Iwa , Ebert Martin , Li Cun , Gschanes Andrea , Witte Otto W. , McDonald Thomas , Nathanielsz Peter W. , Schwab Matthias
Published: December 2006

Background  Maternal antenatal glucocorticoid therapy is used to accelerate lung maturation of immature babies at risk of preterm delivery. It acutely affects brain activity of the human fetus and reduces the immunoreactivity of neurocytoskeletal and synaptic proteins in the fetal baboon brain. These effects might be based on cerebral energy failure due to a decreased neuronal glucose uptake that has been shown in vitro.

Methods  Glucose uptake into the brain is selectively facilitated by GLUT1 expressed in the blood–brain barrier and GLUT3 expressed in the neuronal membrane. Immunohistochemical distribution of GLUT1 and GLUT3 were examined in the frontal neocortex of the fetal baboon brain at 0.73 gestation (i.e. similar to 28 weeks of human gestation) after maternal betamethasone administration, mimicking the clinical dose regimen.

Results  Betamethasone did not alter GLUT1 and GLUT3 immunoreactivity.

Conclusions  The results suggest that inhibition of glucose uptake is not the mechanism for the cerebral effects of antenatal glucocorticoids.
Molecular markers of circulating melanoma cells
Authors: Medic Sandra , Pearce Robert L. , Heenan Peter J. , Ziman Mel
Published: December 2006

Of all skin cancers, cutaneous malignant melanoma (CMM) is the most aggressive and the life expectancy of patients with lymphatic or systemic metastases is dramatically reduced. Understandably therefore, scientists and clinicians have focused on improving diagnostic and prognostic techniques. Of these, perhaps the most promising are multimarker real‐time RT‐PCR and microarray for detection of circulating CMM cells in peripheral blood. While the optimal set of markers is still to be identified that can accurately assess disease severity and progression at all clinical stages of the disease, recent progress has been dramatic. Here we provide an exhaustive review of recent studies in which a variety of markers are assessed. Moreover, the efficacy of the markers relative to clinical stage is discussed in light of experimental findings. From these studies, it is apparent that researchers are now much closer to defining a set of markers of circulating cells that can be utilized in routine diagnostic tests.
The differing embryonic origins of retinal and uveal (iris/ciliary body and choroid) melanosomes are mirrored by their phospholipid composition
Authors: Ward Weslyn C. , Simon John D.
Published: December 2006

The phospholipids present in uveal (iris/ciliary body and choroid) and retinal bovine ocular melanosomes were identified using mass spectrometry. Similar phospholipid content is found for the two types of uveal melanosome, with sphingomyelin being the major species. Significant differences are found between the uveal and retinal melanosome. Glycerophosphoethanolamine (GPEtn) is the major species in the retinal pigment epithelium (RPE); 93% of the GPEtn contain polyunsaturated fatty acids, notably docosahexanoic acid and arachidonic acid, in the sn‐2 position. RPE melanosomes also contain detectable quantities of glycerophosphoserine and glycerophosphate; these species were not detected in the uveal samples. While the structural and functional roles of melanosomal lipids largely remain to be determined, these different lipid compositions reported herein offer new insights into the roles of melanosomes in the different ocular tissues.
Expression of fibronectin‐binding integrins in gingival epithelium in drug‐induced gingival overgrowth
Authors: Walsh P. , Häkkinen L. , Pernu H. , Knuuttila M. , Larjava H.
Published: December 2006

Background and Objective:  Gingival overgrowth is a side‐effect of nifedipine and cyclosporin medications. Integrins are transmembrane glycoproteins that mediate cell adhesion, regulate cell proliferation and participate in the regulation of tissue fibrosis. The aim of this study was to investigate whether expression of epithelial cell integrins is linked to the development of drug‐induced gingival overgrowth.

Material and Methods:  Human gingival biopsies of patients taking nifedipine, cyclosporin, or a combination of both medications, were used. Expression of the α5β1, αvβ1 and αvβ6 integrins, and of cellular extra domain A of fibronectin, was localized in frozen sections using immunohistochemistry.

Results:  The activated conformation of the β1, α5β1 and αvβ6 integrins were more frequently expressed in distinct locations in the oral epithelium in the combined drug group. Cellular extra domain A of fibronectin, a ligand for both α5β1 and αvβ6 integrins, was expressed within the connective tissue of all groups. It was also expressed around the basal keratinocytes of the control, nifedipine and cyclosporin‐induced gingival overgrowth groups, but not in the combined medication group. No relationship between the presence of inflammation and integrin expression was found.

Conclusion:  The results indicate that expression of certain integrins is up‐regulated in the epithelium of drug‐induced gingival overgrowth where they could participate in controlling the formation of elongated rete ridges and tissue fibrosis.
Tetraspanins as Regulators of Protein Trafficking
Authors: Berditchevski Fedor , Odintsova Elena
Published: December 2006

Small transmembrane proteins of the tetraspanin superfamily are believed to function as the main structural blocks of specialized membrane microdomains (referred to as tetraspanin‐enriched microdomains, TERM or TEM). Through a multitude of homotypic and heterotypic interactions, tetraspanins regulate lateral clustering and, consequently, signalling involving adhesion and growth factor receptors as well as costimulatory proteins. The presence of major histocompatibility complex (MHC) I and MHCII molecules in TERM led to suggestion of tetraspanins’ involvement in antigen presentation. In addition, certain tetraspanins function as viral co‐receptors and may be important for viral egress from infected cells. It has recently become apparent that in addition to their purely structural function as organizers of TERM, tetraspanins also regulate various aspects of trafficking and biosynthetic processing of associated receptors. Here, we review recent studies, which specifically focus on this issue.
The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia
Authors: Wolinsky T. D. , Swanson C. J. , Smith K. E. , Zhong H. , Borowsky B. , Seeman P. , Branchek T. , Gerald C. P.
Published: December 2006

Trace amines have been implicated in a number of neuropsychiatric disorders including depression and schizophrenia. Although long known to modulate neurotransmission indirectly through the release of catecholamines, the identification of the Trace Amine 1 receptor (TA1) offers a mechanism by which trace amines can influence synaptic activity directly. TA1 binds and is activated by trace amines such as β‐phenylethylamine and tyramine. Our pharmacological characterization of mouse TA1 showed that, as in rat and primate, amphetamine is an agonist at this receptor but with surprisingly high potency. Without selective ligands for TA1 that do not also possess catecholamine‐releasing properties, however, it has not been possible to study its physiological role in the central nervous system. To that end, a line of mice lacking the TA1 receptor was generated to characterize its contribution to the regulation of behavior. Compared with wild‐type littermates, TA1 knockout (KO) mice displayed a deficit in prepulse inhibition. Knockout animals, in which the TA1‐agonist influence of amphetamine was absent, showed enhanced sensitivity to the psychomotor‐stimulating effect of this drug, which was temporally correlated with significantly larger increases in the release of both dopamine and norepinephrine in the dorsal striatum and associated with a 262% increase in the proportion of striatal high‐affinity D2 receptors. TA1 therefore appears to play a modulatory role in catecholaminergic function and represents a potentially novel mechanism for the treatment of neuropsychiatric disorders. Furthermore, the TA1 KO mouse may provide a useful model for the development of treatments for some positive symptoms of schizophrenia.
RhoA, encoding a Rho GTPase, is associated with smoking initiation
Authors: Chen X. , Che Y. , Zhang L. , Putman A. H. , Damaj I. , Martin B. R. , Kendler K. S. , Miles M. F.
Published: December 2006

We used microarray analysis of acute nicotine responses in mouse brain to choose rationale candidates for human association studies on tobacco smoking and nicotine dependence (ND). Microarray studies on the time–course of acute response to nicotine in mouse brain identified 95 genes regulated in ventral tegmental area. Among these, 30 genes were part of a gene network, with functions relevant to neural plasticity. On this basis and their known roles in drug abuse or synaptic plasticity, we chose the genes RhoA and Ywhag as candidates for human association studies. A synteny search identified human orthologs and we investigated their role in tobacco smoking and ND in a human case–control association study. We genotyped five and three single nucleotide polymorphisms from the RhoA and Ywhag genes, respectively. Both single marker and haplotype analyses were negative for the Ywhag gene. For the RhoA gene, rs2878298 showed highly significant genotypic association with both smoking initiation (SI) and ND (P = 0.00005 for SI and P = 0.0007 for ND). In the allelic analyses, rs2878298 was only significant for SI. In the multimarker haplotype analyses, significant association with SI was found for the RhoA gene (empirical global P values ranged from 9 × 10−5 to 10−5). In all multimarker combinations analyzed, with or without inclusion of the single most significant marker rs2878298, identical risk and protective haplotypes were identified. Our results indicated that the RhoA gene is likely involved in initiation of tobacco smoking and ND. Replication and future model system studies will be needed to validate the role of RhoA gene in SI and ND.