bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making sense of hypertrophic scar: a role for nerves
Authors: Scott Jeffrey R. , Muangman Pornprom , Gibran Nicole S. 
Published: August 2007

ABSTRACTHealed partial thickness wounds including burns and donor sites cause hypertrophic scar formation and patient discomfort. For many patients with hypertrophic scars, pruritis is the most distressing symptom, which leads to wound excoriation and chronic wound formation. In spite of the clinical significance of abnormal innervation in scars, the nervous system has been largely ignored in the pathophysiology of hypertrophic scars. Evidence that neuropeptides contribute to inflammatory responses to injury include inflammatory cell chemotaxis, cytokine and growth factor production. The neuropeptide substance P, which is released from nerve endings after injury, induces inflammation and mediates angiogenesis, keratinocyte proliferation, and fibrogenesis. Substance P activity is tightly regulated by neutral endopeptidase (NEP), a membrane bound metallopeptidase that degrades substance P at the cell membrane. Altered substance P levels may contribute to impaired cutaneous healing responses associated with diabetes mellitus or hypertrophic scar formation. Topical application of exogenous substance P or an NEP inhibitor enhances wound closure kinetics in diabetic murine wounds suggesting that diabetic wounds have insufficient substance P levels to promote a neuroinflammatory response necessary for normal wound repair. Conversely, increased nerve numbers and neuropeptide levels with reduced NEP levels in human and porcine hypertrophic scar samples suggest that excessive neuropeptide activity induces exuberant inflammation in hypertrophic scars. Given these observations about the role of neuropeptides in cutaneous repair, neuronal modulation of repair processes at two extremes of abnormal wound healing, chronic non‐healing ulcers in type II diabetes mellitus and hypertrophic scars in deep partial thickness wounds, may provide therapeutic targets.
Hypertrophic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction
Authors: Kloeters Oliver , Tandara Andrea , Mustoe Thomas A. 
Published: August 2007

ABSTRACTHypertrophic scarring poses a clinically relevant problem as it can be cosmetically disfiguring and functionally debilitating. A lack of animal models has hindered an understanding of the pathogenesis and development of new treatment strategies therefore has largely been empiric. Our group has developed a unique hypertrophic scar (HS) model in the rabbit ear. The model has been reproducible, quantifiable, and measurable over a time period of 1 month. We describe the development as well as the reliability and responsiveness of this model to different therapeutic agents, such as TGF‐β blockade, silicone occlusion, and application of collagen‐synthesis inhibitors. Moreover, it has given insights into the mechanism of action of silicone sheeting occlusive treatment and ultimately suggests that the epidermis plays a critical role in the development of HS. Additionally, we will present new data supporting the importance of the epidermis and further clarify the mechanism of action of silicone sheeting. When a semi‐occlusive polyurethane film was left in place for an additional time period, scar formation was reduced. HSs of this model covered with silicone sheets and five layers of Tegaderm® showed a significant scar reduction by 80% compared with wounds with only one layer of Tegaderm®. The HS model in the rabbit ear is a highly reliable, responsive, and practical model for studying scar tissue behavior. Furthermore, our data suggest that the degree and the duration of occlusion are most important for reducing scar tissue formation.
Role of keratinocyte–fibroblast cross‐talk in development of hypertrophic scar
Authors: Ghahary Aziz , Ghaffari Abdi 
Published: August 2007

ABSTRACTThe ability to generate or repair injured tissue is essential to the continuity of human life. As in all other organs, wound healing in the skin is a dynamic process involving tissue response to different types of insults. This process involves a continuous sequence of signals and responses in which platelets, fibroblasts, epithelial, endothelial, and immune cells come together outside their usual domains to orchestrate a very complex event that results in tissue repair. These signals, which are mainly growth factors and cytokines, orchestrate the initiation, continuation, and termination of wound healing. An imbalance in the synthesis and release of these cytokines and growth factors at the wound site, therefore, may result in either retarded wound healing, as is seen in diabetic patients and the elderly population, or overhealing wounds such as fibroproliferative disorders frequently seen following surgical incision, traumatic wounds, and severe electrical and thermal injury. In general, regardless of the site of injury, in any phase of the dynamic healing process, a fine balance between synthesis of extracellular matrix and degradation by a large family of enzymes, known as matrix metalloproteinases, is required for maintaining the structural integrity of healing tissue. The availability of new models such as organotypic co‐culture systems have allowed us to gain new insight into the cell–cell interactions at both cellular and molecular levels. Recent evidence indicates that mesenchymal–epithelial interactions play a critical role in regulation of skin homeostasis and this cross‐talk is mediated by soluble factors acting as autocrine/paracrine regulators of fibroblast and keratinocyte growth, function, and differentiation. In this review we address the question of how keratinocyte–fibroblast interaction plays a role in controlling the expression of key extracellular matrix molecules such as matrix metalloproteinases, which are critical in the healing process following any types of insults to the skin.
Blood donor screening for parvovirus B19 in Germany and Austria
Authors: Schmidt Michael , Themann Anna , Drexler Camilla , Bayer Michaela , Lanzer Gerhard , Menichetti Eva , Lechner Sigrid , Wessin Dietmar , Prokoph Barbara , Allain Jean‐Pierre , Seifried Erhard , Kai Hourfar Michael 
Published: August 2007

BACKGROUND:Although the main transmission pathway of parvovirus B19 (B19) is typically via the respiratory route, several transfusion‐transmitted infections have been reported. To increase blood safety, all blood donations to our blood donor service have been screened by a B19 minipool real‐time nucleic acid testing (NAT) since April 2000. Additional customers have been screened since the summer of 2003.STUDY DESIGN AND METHODS:In total, 2.8 million donations from Germany and Austria were screened for B19 by real‐time minipool NAT. A subgroup of 50 B19 DNA–positive donors was screened for B19 immunoglobulin G (IgG) and IgM antibodies and B19 DNA over a 6‐month period. Results were compared to those of 100 B19 DNA–negative donors.RESULTS:Data accumulated over the past 6 years indicate a high incidence period from May 2004 to January 2006. In total, the incidence was 12.7 and 261.5 per 100,000 donations with high virus loads equal to or above 105and below 105IU per mL, respectively. Median virus concentration in the case group was 4.85 × 107 IU per mL at Time Point T0 and was reduced to 4 × 102 IU per mL at the time of the next donation (3 months later). Neutralizing antibodies (VP2) were detected in all donations if virus load was reduced to less than 105 IU per mL.CONCLUSION:The release of B19 DNA–positive blood products with a concentration of less than 105 IU per mL is thought to be safe due to the high level of neutralizing VP2 antibodies and is currently examined in a donor recipient infectivity study. In contrast, blood products with a high B19 DNA concentration (≥105 IU/mL), some of which did not contain neutralizing antibodies, were discarded to protect at risk individuals.
Detection of anti‐D in D– recipients transfused with D+ red blood cells
Authors: Yazer Mark H. , Triulzi Darrell J. 
Published: August 2007

BACKGROUND: The D antigen is highly immunogenic, requiring only a small quantity of transfused red blood cells (RBCs) to cause alloimmunization in D– immunocompetent recipients. The relatively low sensitization rate in oncology patients transfused with D+ platelets is well documented. A study of the alloimmunization rate of primarily nononcology D– recipients transfused with D+ RBCs was undertaken.STUDY DESIGN AND METHODS: Transfusion service records were examined to identify D– recipients who were not alloimmunized to the D antigen and who had a follow‐up antibody screen performed at least 10 days after the initial D+ RBC transfusion(s). The age and sex of the recipients, date and number of D+ RBC transfusion(s) and their leukoreduction status, all subsequent serologic investigations, and the hospital ward where the units were issued were recorded.RESULTS: There were 98 study‐eligible recipients identified who received a total of 445 D+ RBC units. The mean follow‐up length was 182 days. Most recipients (87%) had antibody screens performed more than 21 days after the initial D+ RBC transfusion. In total, 24 recipients made 44 new alloantibodies: 22 anti‐D (22%), 11 anti‐E, 5 anti‐C, 2 anti‐K, and 1 each of anti‐Kpa, anti‐Jka, anti‐Bg, and anti‐Fyb. The rate of anti‐D alloimmunization among recipients of entirely leukoreduced D+ units was 13 percent (1/8). Reexposure to D+ RBCs after the initial bleeding episode did not increase the rate of alloimmunization.CONCLUSIONS: The 22 percent rate of anti‐D alloimmunization in patients requiring urgent RBC transfusion was intermediate between the rates previously reported for D– oncology patients transfused with D+ RBCs and that in immunocompetent volunteer recipients.
Divergent expression of cellular prion protein on blood cells of human and nonhuman primates
Authors: Holada Karel , Simak Jan , Brown Paul , Vostal Jaroslav G. 
Published: August 2007

BACKGROUND: Four recent transmissions of variant Creutzfeldt‐Jakob disease infection by transfusion highlight the need for detailed understanding of blood‐related prion pathogenesis. Nonhuman primates are the most relevant models of human prion diseases.STUDY DESIGN AND METHODS: Quantitative flow cytometry with monoclonal antibodies FH11, 3F4, and 6H4 against different parts of the normal cellular form of the prion protein (PrPC) was used to evaluate its expression on blood cells of humans, chimpanzees, cynomolgus macaques, rhesus macaques, squirrel monkeys, and microcebe lemurs.RESULTS: Chimpanzees, rhesus macaques, and squirrel monkeys displayed a much higher quantity of total blood cell membrane PrPC than humans, due to a markedly higher expression of PrPC on their red blood cells (RBCs). In contrast, cynomolgus macaques and lemurs demonstrated substantially lower levels of membrane PrPC due to the lack of significant PrPC expression on RBCs and platelets (PLTs). All species displayed PrPC on white blood cells (WBCs), with the highest levels found on human cells. Only humans, chimpanzees, and to a lesser degree rhesus macaques expressed PrPC on PLTs.CONCLUSION: If PrPC contributes to the propagation or transport of prion infectivity in blood, the differences reported here need to be considered when extrapolating results of transmission studies in primate models to blood and blood components in humans.
Altered processing of thawed red cells to improve the in vitro quality during postthaw storage at 4°C
Authors: Lagerberg Johan W.M. , Truijens‐de Lange Rosa , De Korte Dirk , Verhoeven Arthur J. 
Published: August 2007

BACKGROUND: The use of a functionally closed system (ACP215, Haemonetics) for the glycerolization and deglycerolization of red blood cell (RBC) units allows for prolonged postthaw storage. In this study, the postthaw quality of previously frozen, deglycerolized RBCs resuspended in saline‐adenine‐glucose‐mannitol (SAGM) or additive solution AS‐3 was investigated.STUDY DESIGN AND METHODS: Leukoreduced RBC units were frozen with 40 percent glycerol and stored at −80°C for at least 14 days. The thawed units were deglycerolized with the ACP215, resuspended in SAGM or AS‐3, and stored at 2 to 6°C for up to 21 days.RESULTS: The mean ± standard deviation in vitro freeze‐thaw‐wash recovery was 81 ± 5 percent. During storage, hemolysis of deglycerolized cells remained below 0.8 percent for 2 days in SAGM and for 14 days in AS‐3. This difference was explained by the protective effect of citrate, which is present in AS‐3. Cells stored in AS‐3 showed a lower glycolytic activity and a faster decline in adenosine 5′‐triphosphate (ATP) than cells in SAGM. Increasing the internal pH of cells before storage in AS‐3 by use of phosphate‐buffered saline (PBS) in the deglycerolization procedure resulted in elevated lactate production and better maintenance of intracellular ATP content. After 3 weeks of storage, the ATP content of PBS‐washed cells amounted to 2.5 ± 0.5 µmol per g of hemoglobin (Hb), whereas for saline/glucose‐washed cells this value was decreased to 1.0 ± 0.3 µmol per g of Hb.CONCLUSIONS: Leukoreduced, deglycerolized RBCs can be stored for 48 hours in SAGM. Improved ATP levels during refrigerated storage can be observed with thawed cells, resuspended in AS‐3, when PBS is used as a washing solution.
Translation of glycoprotein IIIa in stored blood platelets
Authors: Thon Jonathan N. , Devine Dana V. 
Published: August 2007

BACKGROUND: Platelet (PLT) products have a short shelf life (5 days) owing in part to the deterioration of the quality of PLTs stored at 22°C. This creates significant inventory challenges, and blood banks may suffer shortages and high wastage as a result. The precise biochemical pathways involved in the PLT storage lesion are unknown and must be understood before storage time can be extended.STUDY DESIGN AND METHODS: Informed by previous proteomics analysis, specific PLT glycoprotein (GP) concentration and surface expression were examined by Western blot and flow cytometry. mRNA concentration was determined by Northern blot and real‐time polymerase chain reaction. Protein synthesis was confirmed by [35S]methionine labeling.RESULTS: Western blots of GPIIIa revealed a twofold increase in concentration on Day 7 of storage and a fourfold increase on Day 10. By flow cytometry, surface expression of the GPIIb/IIIa increased by 13.4 percent on Day 7 and 41.9 percent on Day 10. Full‐length GPIIIa mRNA was present throughout this storage period and was shown to have a half‐life of approximately 2.9 days. Translation of GPIIb and IIIa during storage was confirmed by [35S]methionine labeling.CONCLUSION: This article confirms that PLTs are capable of synthesizing biologically relevant proteins ex vivo throughout a 10‐day storage period with particularly long‐lived mRNA and provides a framework through which the biochemical mechanisms involved in the translational regulation of proteins thought to be involved in the initiation or exacerbation of the PLT storage lesion can be investigated.
Impact of Different Pacing Modes on Left Ventricular Contractility Following Cardiopulmonary Bypass
Authors: BAKHTIARY FARHAD , DOGAN SELAMI , DZEMALI OMER , ACKERMANN HANNS , KLEINE PETER , SCHÄCHINGER VOLKER , MORITZ ANTON , AYBEK TAYFUN 
Published: August 2007

Background: Acute left ventricular (LV) dysfunction after cardiopulmonary bypass (CBP) is a serious complication in cardiac surgery. The aim of this study was to investigate the effect of different epicardial pacing modes on LV contractility and changes of myocardial oxygen extraction (MVO2) following CPB in an animal model. The utility of conductance catheter measurement versus left ventricular outflow tract mean systolic acceleration (LVOTAcc) for quantification of LV function was evaluated.
Methods: Fourteen piglets underwent median sternotomy and CPB for 90 minutes, myocardial ischemia for 60 minutes, and reperfusion for 30 minutes. Different pacing modes were obtained before and after CPB to investigate changes in LV function. LV Function was quantified by end‐systolic‐pressure‐volume relationships (ESPVR) as measured by the conductance catheter method and by LVOTAcc obtained from transepicardial echocardiographic studies.
Results: LV contractility improved significantly by biventricular and atrial pacing compared with natural sinus rhythm (SR). MVO2 remained stable or even decreased with biventricular pacing after surgery compared with SR. Right ventricular pacing resulted in poor LV‐function with a rise of MVO2. LVOTAcc showed a strong correlation to invasively measured ESPVR.
Conclusion: Postoperative biventricular pacing was associated with an improved LV contractility without rise of MVO2 compared with SR and atrial pacing. At termination of CPB, this appears to facilitate the management of LV failure and potentially may reduce the need for inotropic support, additionally protecting myocardial metabolism. The echocardiographic assessment of LVOTAcc was a simple and reliable as well as effective method to quantify LV contractility and showed a good correlation with the more invasive conductance catheter.
An Approach to “Ablate and Pace”:AV Junction Ablation and Pacemaker Implantation Performed Concurrently from the Same Venous Access Site
Authors: ISSA ZIAD F. 
Published: August 2007

Background: Atrioventricular junction (AVJ) ablation combined with permanent pacemaker implantation (the “ablate and pace” approach) remains an acceptable alternative treatment strategy for symptomatic, drug‐refractory atrial fibrillation (AF) with rapid ventricular response. This case series describes the feasibility and safety of catheter ablation of the AVJ via a superior vena caval approach performed during concurrent dual‐chamber pacemaker implantation.
Methods: A total of 17 consecutive patients with symptomatic, drug‐refractory, paroxysmal AF underwent combined AVJ ablation and dual‐chamber pacemaker implantation procedure using a left axillary venous approach. Two separate introducer sheaths were placed into the axillary vein. The first sheath was used for implantation of the pacemaker ventricular lead, which was then connected to the pulse generator. Subsequently, a standard ablation catheter was introduced through the second axillary venous sheath and used for radiofrequency (RF) ablation of the AVJ. After successful ablation, the catheter was withdrawn and the pacemaker atrial lead was advanced through that same sheath and implanted in the right atrium.
Results: Catheter ablation of the AVJ was successfully achieved in all patients. The median number of RF applications required to achieve complete AV block was three (range 1–10). In one patient, AV conduction recovered within the first hour after completion of the procedure, and AVJ ablation was then performed using the conventional femoral venous approach. There were no procedural complications.
Conclusion: Catheter ablation of the AVJ can be performed successfully and safely via a superior vena caval approach in patients undergoing concurrent dual‐chamber pacemaker implantation.
Effect of Dl‐Sotalol on Mortality and Recurrence of Ventricular Tachyarrhythmias:Ischemic Compared to Nonischemic Cardiomyopathy
Authors: FURUSHIMA HIROSHI , CHINUSHI MASAOMI , OKAMURA KAZUKI , KOMURA SATORU , TANABE YASUTAKA , SATO AKINORI , IZUMI DAISUKE , AIZAWA YOSHIFUSA 
Published: August 2007

Objective:

We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD).
Patients:

Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%± 10% vs. 35%± 12%),
Results:

After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow‐up period of 47 ± 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all‐cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS.
Conclusion:

Sotalol reduced the overall VTA recurrence rate and all‐cause mortality more in CAD than in IDCM.
In vitro activity of daptomycin and tigecycline against coagulase‐negative staphylococcus blood isolates from bone marrow transplant recipients
Authors: Kratzer Christina , Rabitsch Werner , Hirschl Alexander M. , Graninger Wolfgang , Presterl Elisabeth 
Published: August 2007

AbstractBackground and objective:  Multi‐resistant coagulase‐negative staphylococci (CNS) may cause systemic infections in patients undergoing bone marrow transplantation. Daptomycin, a new lipopeptide, and tigecycline, a new glycylcycline, have excellent activity against Gram‐positive bacteria including methicillin‐resistant staphylococci. This study presents the in vitro activity of daptomycin and tigecycline compared to vancomycin and fosfomycin against 105 CNS isolated from 76 bone marrow transplant patients with symptomatic bacteremia.Material and methods:  Blood stream isolates of Staphylococcus epidermidis (n = 102) and Staphylococcus haemolyticus (n = 3) from bone marrow transplant patients were collected from 2000 to 2006. The susceptibility of all isolates was tested using methods of the Clinical Laboratory Standards Institute.Results:  The minimal inhibitory concentrations MIC50 and MIC90 were 0.125 μg/mL and 0.25 μg/mL for daptomycin, 0.25 and 0.5 μg/mL for tigecycline, 1 μg/mL and 2 μg/mL for vancomycin, and 8 μg/mL and >256 μg/mL for fosfomycin, respectively. MIC values of tested agents were similar for both methicillin‐sensitive and methicillin‐resistant S. epidermidis strains.Conclusions:  All CNS isolates were susceptible to the new antistaphylococcal agents daptomycin and tigecycline. Although vancomycin had been used over the past 30 yr at our bone marrow transplant unit all CNS were still susceptible to vancomycin.
The Utopian Dimension of Kafka's “In The Penal Colony”
Authors: Hadomi Leah 
Published: August 2007

“In the Penal Colony” incorporates the dilemma of Utopia expressed in a continuum from the Utopian spiritual longing to its material Dystopian realization and the Anti‐Utopian attempt to retreat from it. The spatial and temporal background of the story is portrayed as a movement from centrality and timelessness (Utopian) to peripherness and sequential time (Dystopian and Anti‐Utopian). The spiritually closed, homogeneous, and coherent Utopian world of the Old Commandant turns into Dystopian nightmare while being implemented by the machine and leads to a retreat to the Anti‐Utopian world of the colony.The “stranger,” the “guide” and the “common member,” representative figures of the Utopian genre, are projected into a Kafkaesque world as characterised by the stranger, explorer, officer, condemned man and soldier. Kafka's unique clustering of figures emphasises the Utopian dilemma. A feeling of anguish is expressed in the description of three meaningful moments of “silence,” placed at significant points within the structure and expressing the experience of “… guilt (that) is never to be doubted” in the Penal Colony.