bluuebunny/crossref_metadata_2025_split huggingface dataset:
The management of genital lymphoedema
Authors: Garaffa Giulio , Christopher Nim , Ralph David J. 
Published: March 2008

OBJECTIVESTo report our experience and management of genital lymphoedema, as this condition can be extremely debilitating and difficult to manage.PATIENTS AND METHODSThe clinical records of 90 patients with genital lymphoedema who presented between 1998 and 2007 were retrospectively reviewed. The surgical management of 34 patients consisted of the excision of the affected skin and of the subcutaneous layers. This involved scrotal excision in 15 patients with primary closure. Skin grafts were required in seven patients for penile shaft cover. The results for cosmesis, recovery of sexual function, patient’s satisfaction and complications are discussed.RESULTSIn all, 56 patients were successfully managed conservatively by treating the underlying condition, antibiotic administration, compression and elevation of the genitalia. The remaining 34 patients required surgical management with an overall excellent cosmetic result and a significant improvement in sexual function.CONCLUSIONSWhen surgery is necessary for genital lymphoedema, the new techniques described provide excellent cosmetic and functional results.
Intensifying the saturation biopsy technique for detecting prostate cancer after previous negative biopsies: a step in the wrong direction
Authors: Simon Jörg , Kuefer Rainer , Bartsch Georg , Volkmer Björn G. , Hautmann Richard E. , Gottfried Hans‐Werner 
Published: March 2008

OBJECTIVETo report the results using an extensive saturation biopsy in men with negative prostate biopsies but in whom there is still a clinical suspicion for carcinoma.PATIENTS AND METHODSBetween February 1999 and October 2004 we offered 40 patients (median age 63 years) an extensive saturation biopsy if there was clinical suspicion of prostate cancer after previous negative prostate biopsies. The median (range) number of cores taken was 64 (39–139) and was adjusted to the size of the prostate. All patients received general or spinal anaesthesia.RESULTSOf the 40 patients, 18 (45%) had carcinoma in at least one core; 16 had a radical prostatectomy, which showed pT2a, pT2b, pT2c, pT3a and pT3b adenocarcinoma of the prostate in three, four, six, two and one patients, respectively. Brachytherapy and external radiation were the therapies of choice in the other patients. Sixteen patients had marked haematuria after the biopsy procedure.CONCLUSIONThere is no significant increase in the cancer detection rate in an extensive saturation‐biopsy regimen compared to published series with fewer cores, but the morbidity increased.
Retroperitoneal lymph node dissection after chemotherapy for germ cell tumours: is a full bilateral template always necessary?
Authors: Steiner Hannes , Peschel Reinhard , Bartsch Georg 
Published: March 2008

OBJECTIVETo evaluate the long‐term oncological outcome in selected patients treated for nonseminomatous germ cell tumours (NSGCT) with a retroperitoneal lymph node dissection after chemotherapy (pcRPLND) and not using the full bilateral template.PATIENTS AND METHODSFrom 1988 to 2005, 102 patients with retroperitoneal stage II NSGCT, who at initial presentation had metastases in the primary retroperitoneal site only, had pcRPLND within a restricted template, whether computed tomography showed complete or incomplete remission. In all, 78 patients had a unilateral template dissection and 24 an open modified template dissection.RESULTSOf the 102 patients, 30 had stage IIC, 63 IIB, and nine tumour marker‐positive stage IIA disease. Active tumour was found in two RPLND specimens; mature teratoma in 46 of the 102 patients, and necrosis/fibrosis in 54. Antegrade ejaculation was preserved in all 78 patients who had unilateral RPLND and in 18 of 24 who had a modified RPLND (overall antegrade ejaculation rate 94%). During a median follow‐up of 102 months there were only three recurrences, two outside the retroperitoneum and one in the retroperitoneum. Only the latter was retrocaval, above the level of the inferior mesenteric artery within the boundaries of a full bilateral RPLND. This patient had had left unilateral template dissection after chemotherapy for IIC disease which was restricted to the para‐aortic nodes.CONCLUSIONIn a selected group of patients with stage II NSGCT, pcRPLND within the modified template might be oncologically efficient and allow ejaculation to be preserved.
Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma
Authors: Rubio‐Del‐Campo Antonio , Salinas‐Sánchez Antonio S. , Sánchez‐Sánchez Francisco , Giménez‐Bachs José M. , Donate‐Moreno María J. , Pastor‐Navarro Héctor , Carrión‐López Pedro , Escribano Julio 
Published: March 2008

OBJECTIVESTo analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).MATERIALS AND METHODSSpecimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.RESULTSMSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.CONCLUSIONSOur data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.
HUMAN NATURE AND ENHANCEMENT
Authors: BUCHANAN ALLEN 
Published: March 2008

ABSTRACTAppeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good.I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.
GIVING ADDICTS THEIR DRUG OF CHOICE: THE PROBLEM OF CONSENT
Authors: WALKER TOM 
Published: March 2008

ABSTRACTResearchers working on drug addiction may, for a variety of reasons, want to carry out research which involves giving addicts their drug of choice. In carrying out this research consent needs to be obtained from those addicts recruited to participate in it. Concerns have been raised about whether or not such addicts are able to give this consent. Despite their differences, however, both sides in this debate appear to be agreed that the way to resolve this issue is to determine whether or not addicts have irresistible cravings for drugs – if they do, then they cannot consent to this type of research; if they do not, then they can. This I will argue is a mistake. Determining whether or not addicts can say ‘No’ to offers of drugs will not help us to make much progress here. Instead we need to look at the various ways in which different types of research may undermine an addict's competence to give consent. What we will find is that the details of the research make a big difference here and that, as such, we need to steer a course between, on the one hand, painting all addicts as being unable to consent to research which involves providing them with drugs, and, on the other, maintaining that there are no problems in obtaining consent from addicts to take part in such research.
Update and Analysis of the University College London Low Density Lipoprotein Receptor Familial Hypercholesterolemia Database
Authors: Leigh S. E. A. , Foster A. H. , Whittall R. A. , Hubbart C. S. , Humphries S. E. 
Published: March 2008

SummaryFamilial hypercholesterolemia (FH) (OMIM 143890) is most commonly caused by variations in the LDLR gene which encodes the receptor for Low Density Lipoprotein (LDL) cholesterol particles. We have updated the University College London (UCL) LDLR FH database (http://www.ucl.ac.uk/ldlr) by adding variants reported in the literature since 2001, converting existing entries to standard nomenclature, and transferring the database to the Leiden Open Source Variation Database (LOVD) platform. As of July 2007 the database listed 1066 unique LDLR gene events. Sixty five percent (n = 689) of the variants are DNA substitutions, 24% (n = 260) small DNA rearrangements (<100bp) and 11% (n = 117) large DNA rearrangements (>100bp), proportions which are similar to those reported in the 2001 database (n = 683, 62%, 24% and 14% respectively). The DNA substitutions and small rearrangements occur along the length of the gene, with 24 in the promoter region, 86 in intronic sequences and 839 in the exons (93 nonsense variants, 499 missense variants and 247 small rearrangements). These occur in all exons, with the highest proportion (20%) in exon 4 (186/949); this exon is the largest and codes for the critical ligand binding region, where any missense variant is likely to be pathogenic. Using the PolyPhen and SIFT prediction computer programmes 87% of the missense variants are predicted to have a deleterious effect on LDLR activity, and it is probable that at least 48% of the remainder are also pathogenic, but their role in FH causation requires confirmation by in vitro or family studies.
BMP inhibition enhances axonal growth and functional recovery after spinal cord injury
Authors: Matsuura Iichiro , Taniguchi Junko , Hata Katsuhiko , Saeki Naokatsu , Yamashita Toshihide 
Published: March 2008

AbstractBone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor‐β superfamily. BMPs regulate several crucial aspects of embryonic development and organogenesis. The reemergence of BMPs in the injured adult CNS suggests their involvement in the pathogenesis of the lesion. Here, we demonstrate that BMPs are potent inhibitors of axonal regeneration in the adult spinal cord. The expression of BMP‐2/4 is elevated in oligodendrocytes and astrocytes around the injury site following spinal cord contusion. Intrathecal administration of noggin – a soluble BMP antagonist—leads to enhanced locomotor activity and reveals significant regrowth of the corticospinal tract after spinal cord contusion. Thus, BMPs play a role in inhibiting axonal regeneration and limiting functional recovery following injury to the CNS.
Subepidermal moisture differentiates erythema and stage I pressure ulcers in nursing home residents
Authors: Bates‐Jensen Barbara M. , McCreath Heather E. , Pongquan Voranan , Apeles Neil Christopher R. 
Published: March 2008

ABSTRACTThe objective of this descriptive cohort study was to examine the relationship between subepidermal moisture (SEM) and visual assessment of early pressure ulcers (PUs) in 31 nursing home (NH) residents residing in two NHs. Concurrent visual assessments and SEM were obtained at the sacrum, right and left trochanters, buttocks, and ischium weekly for 20 weeks. Visual assessment was rated as normal, erythema, stage I PU, or stage II+ PU. SEM, measured with a dermal phase meter where higher readings indicate greater SEM (range: 0–999 dermal phase units [DPU]), was modeled as a predictor of concurrent visual assessment of skin damage and erythema and stage I PUs at the sacrum 1 week later with covariate PU risk. Participants had a mean age of 84.1 years, were 83% female, 72% non‐Hispanic white. SEM was lowest for normal skin (104 DPU, SD 114), higher for erythema (185 DPU, SD 138), stage I PUs (264 DPU, SD 208), and highest for stage II+ PUs (727 DPU, SD 287) across all sites (all p<0.01). SEM was responsive to visual assessment changes, differentiated between erythema and stage I PU, and higher SEM predicted greater likelihood of erythema/stage I PU at the sacrum the next week (odds ratio=1.32 for every 100 DPU increase, p=0.03). SEM was associated with concurrent skin damage and future (1 week later) development of sacral erythema/stage I PUs. SEM differentiates between erythema and stage I PUs. SEM may assist in predicting early PU damage, allowing for earlier intervention to prevent PUs.
Use of a novel porcine collagen paste as a dermal substitute in full‐thickness wounds
Authors: Shevchenko Rostislav V. , Sibbons Paul D. , Sharpe Justin R. , James S. Elizabeth 
Published: March 2008

ABSTRACTA commercially available porcine collagen sheet material has been found previously to be useful as an implant for reconstructive surgery. However, its use as a dermal substitute has been hindered by slow cell penetration and vascularization. A novel paste formulation of this material was investigated for its potential role as a dermal substitute in full‐thickness wounds. A porcine punch biopsy model was initially used to assess the integration of a wide range of material formulations. Selected formulations were then assessed further in a larger wound‐chamber model. Paste formulations were compared with those of sheet and another commercially available dermal regeneration template. The porcine collagen paste became integrated into full‐thickness wounds without rejection and without excessive inflammation. It was detected in wounds up to day 27 postimplantation. Porcine collagen paste was readily infiltrated by host cells by day 2 and supported migrating keratinocytes on its surface. Staining for endothelial cells indicated neovasculature formation as early as day 4 and functional newly formed microvessels were noted at day 7. This was comparable with neovascularization of an alternative and clinically proven dermal regeneration template and was significantly superior to the sheet material formulation at the same time points. Our findings suggest that porcine collagen paste may be suitable as an alternative to current dermal substitutes in full‐thickness wounds.
Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse
Authors: Galeano Mariarosaria , Bitto Alessandra , Altavilla Domenica , Minutoli Letteria , Polito Francesca , Calò Margherita , Lo Cascio Patrizia , Stagno d'Alcontres Francesco , Squadrito Francesco 
Published: March 2008

ABSTRACTHealing of diabetic wounds still remains a critical medical problem. Polydeoxyribonucleotide (PDRN), a compound having a mixture of deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic or adverse effect. We studied the effects of PDRN in diabetes‐related healing defect using an incisional skin‐wound model produced on the back of female diabetic mice (db+/db+) and their normal littermates (db+/+m). Animals were treated daily for 12 days with PDRN (8 mg/kg/ip) or its vehicle (100 μL 0.9%NaCl). Mice were killed 3, 6, and 12 days after skin injury to measure vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, to assay angiogenesis and tissue remodeling through histological evaluation, and to study CD31, Angiopoietin‐1 and Transglutaminase‐II. Furthermore, we measured wound breaking strength at day 12. PDRN injection in diabetic mice resulted in an increased VEGF message (vehicle=1.0±0.2 n‐fold vs. β‐actin; PDRN=1.5±0.09 n‐fold vs. β‐actin) and protein wound content on day 6 (vehicle=0.3±0.07 pg/wound; PDRN=0.9±0.1 pg/wound). PDRN injection improved the impaired wound healing and increased the wound‐breaking strength in diabetic mice. PDRN also caused a marked increase in CD31 immunostaining and induced Transglutaminase‐II and Angiopoietin‐1 expression. Furthermore, the concomitant administration of 3,7‐dimethyl‐1‐propargilxanthine, a selective adenosine A2A receptor antagonist, abolished PDRN positive effects on healing. However, 3,7‐dimethyl‐1‐propargilxanthine alone did not affect wound healing in both diabetic mice and normal littermates. These results suggest that PDRN might be useful in wound disorders associated with diabetes.
The mast cell stabilizer ketotifen prevents development of excessive skin wound contraction and fibrosis in red Duroc pigs
Authors: Gallant‐Behm Corrie L. , Hildebrand Kevin A. , Hart David A. 
Published: March 2008

ABSTRACTSkin wound healing in Yorkshire pigs closely approximates human wound healing. Conversely, red Duroc pigs form fibroproliferative, hypercontractile scars. As mast cells have been implicated in several fibrotic conditions, the present study used these models to evaluate the potential role of mast cells in wound contraction and fibrosis. Immediately following the creation of full‐thickness excisional wounds, the mast cell stabilizer ketotifen was used to treat both Yorkshire and red Durocs. Control red Durocs showed significantly more wound contraction than Yorkshires, both before and after reepithelialization. Ketotifen treatment significantly reduced the first phase of contraction in red Duroc wounds to a level equivalent to Yorkshire wounds, but had no detectable effect on the postepithelialization phase of contraction. Cessation of drug treatment after 10 weeks did not lead to resumption of excessive contraction in red Durocs, indicating that ketotifen blocked rather than delayed such contraction during a critical phase of healing. Ketotifen treatment also reduced the deposition of collagen within the red Duroc wounds, but did not affect Yorkshire wound contraction or collagen deposition. These results suggest that ketotifen may be an effective treatment for the reduction of excessive wound contraction and fibrosis in human cutaneous injuries, without affecting the normal healing process.
Altered tissue repair in hevin‐null mice: Inhibition of fibroblast migration by a matricellular SPARC homolog
Authors: Sullivan Millicent M. , Puolakkainen Pauli A. , Barker Thomas H. , Funk Sarah E. , Sage E. Helene 
Published: March 2008

ABSTRACTMatricellular proteins such as hevin, secreted protein acidic and rich in cysteine, and thrombospondin‐2 play an important role during tissue repair through their influence on fundamental cellular activities such as adhesion, migration, proliferation, and extracellular matrix synthesis/reorganization. We have investigated the role played by hevin during excisional and incisional cutaneous wound repair in hevin‐null mice. Hevin‐null animals both close and heal their skin wounds faster than wild‐type animals, as evidenced by enhanced macrophage infiltration of wound beds at early time points, the earlier appearance of mature extracellular matrix, and the overall higher maturity score. In addition, fibrovascular invasion of polyvinyl alcohol sponges was more robust in hevin‐null mice, a result indicating that differences in cell migration might underlie the observed alterations in wound repair. Experiments in vitro showed that hevin induced the deadhesion and inhibited the migration of primary dermal fibroblasts in a Rac‐1–dependent manner. These findings indicate that the differences in wound repair between hevin‐null and wild‐type animals can be attributed in part to the deadhesive function of hevin and reduced cell migration within dermal wound beds in which this protein is expressed.
Chloritoid–glaucophane schist in the north Qilian orogen, NW China: phase equilibria and P–T path from garnet zonation
Authors: WEI C. J. , SONG S. G. 
Published: March 2008

AbstractChloritoid–glaucophane‐bearing rocks are widespread in the high‐pressure belt of the north Qilian orogen, NW China. They are interbedded and cofacial with felsic schists originated from greywackes, mafic garnet blueschists and low‐T eclogites. Two representative chloritoid–glaucophane‐bearing assemblages are chloritoid + glaucophane + garnet + talc + quartz (sample Q5‐49) and chloritoid + glaucophane + garnet + phengite + epidote + quartz (sample Q5‐12). Garnet in sample Q5‐49 is coarse‐, medium‐ and fine‐grained and shows two types of zonation patterns. In pattern I, Xgrs is constant as Xpy rises, and in pattern II Xgrs decreases as Xpy rises. Phase equilibrium modelling in the NC(K)MnFMASH system with Thermocalc 3.25 indicates that pattern I can be formed during progressive metamorphism in lawsonite‐stable assemblages, while pattern II zonation can be formed with further heating after lawsonite has been consumed. Garnet growth in Q5‐49 is consistent with a continuous progressive metamorphic process from ∼14.5 kbar at 470 °C to ∼22.5 kbar at 560 °C. Garnet in sample Q5‐12 develops with pattern I zonation, which is consistent with a progressive metamorphic process from ∼21 kbar at 540 °C to ∼23.5 kbar at 580 °C with lawsonite present in the whole garnet growth. The latter sample shows the highest P–T conditions of the reported chloritoid–glaucophane‐bearing assemblages. Phase equilibrium calculation in the NCKFMASH system with a recent mixing model of amphibole indicates that chloritoid + glaucophane paragenesis does not have a low‐pressure limit of 18–19 kbar as previously suggested, but has a much larger pressure range from 7–8 to 27–30 kbar, with the low‐pressure part being within the stability field of albite.
Precautionary Insurance Demand With State‐Dependent Background Risk
Authors: Fei Wenan , Schlesinger Harris 
Published: March 2008

AbstractThis article considers a zero‐mean background risk that is uncorrelated with insurable losses, but is not necessarily statistically independent. In particular, the size of the background risk can vary in different insurable‐loss states. We show how a prudent individual will buy either more insurance or less insurance than with no background risk, depending on the relative size of the background risk in the loss states vis‐á‐vis the no‐loss states. If we consider two individuals, with one more risk averse than the other, we need to compare the intensities of their precautionary motives, in addition to their measures of risk aversion, before we can determine who buys more insurance coverage in the presence of the state dependent background risk.