bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penile fracture: preoperative evaluation and surgical technique for optimal patient outcome
Authors: Kamdar Ciamack , Mooppan Unni M.M. , Kim Hong , Gulmi Frederick A. 
Published: August 2008

OBJECTIVETo review the preoperative diagnostic evaluation and surgical treatment of penile fracture, as the condition is a urological emergency that requires immediate surgical exploration and repair.PATIENTS AND METHODSBetween January 2003 and October 2007 eight patients presented to the emergency department with penile fracture after sexual intercourse. The clinical presentation, preoperative evaluation and imaging, surgical technique, and postoperative care were assessed to determine the optimal patient outcome.RESULTSSeven of the eight patients were treated surgically and one refused surgical intervention. Four cases involved unilateral corporal injury, two involved unilateral corporal injury with an associated urethral injury, and one involved bilateral corporal injury with an associated urethral injury. Although retrograde urethrogram were taken of all three urethral injuries, none of them revealed the injury. Diagnostic cavernosography or magnetic resonance imaging were not used in any of the patients. No complications occurred in the patients treated surgically.CONCLUSIONSPreoperative imaging should not delay surgical repair. If an associated urethral injury is suspected, flexible cystoscopy is recommended in the operating room, as opposed to a retrograde urethrogram. A subcoronal circumcising incision is recommended to deglove the entire penile shaft and have complete access to all three corporal bodies, as well as the neurovascular bundle. Saline mixed with indigo carmine can be injected both into the corpora cavernosum or corpus spongiosum via the glans penis, after a tourniquet is placed at the base of the penis, to evaluate the surgical repair and to determine if there are any missed injuries.
Histopathological characteristics of lymph node metastases predict cancer‐specific survival in node‐positive prostate cancer
Authors: Boormans Joost L. , Wildhagen Mark F. , Bangma Chris H. , Verhagen Paul C. , Van Leenders Geert J. 
Published: August 2008

OBJECTIVETo correlate the histopathological characteristics of lymph node metastases in prostate cancer with cancer‐specific survival (CSS).PATIENTS AND METHODSThe histopathological slides from 142 patients who had had a pelvic lymph node dissection for node‐positive prostate cancer were reviewed. For each patient we recorded the number of lymph nodes removed, the number of positive nodes, the diameter of the largest metastasis and extranodal extension (ENE). The lymph node metastases were graded according to the Gleason system. These variables were correlated with CSS.RESULTSThe mean age of the patients was 62.4 years and the mean preoperative prostate‐specific antigen level was 40.2 ng/mL. The median follow‐up was 77.5 months, and the median overall and CSS were 91 and 112 months, respectively. On univariable analysis the following variables correlated with poor CSS: a nodal Gleason score of >7 (hazard ratio 2.4, P < 0.001), a diameter of the largest metastasis of >3 mm (2.2, P = 0.025), more than two lymph node metastases (2.0, P = 0.003), and ENE in more than one lymph node (1.9, P = 0.014). Multivariable analysis showed only the nodal Gleason score and the diameter of the largest metastasis to be independent predictors of CSS (1.8, P = 0.021, and 2.2, P = 0.046, respectively).CONCLUSIONThe histopathological characteristics of lymph node metastases in prostate cancer have predictive value for the clinical outcome. The nodal Gleason score and the diameter of the largest metastasis are independent predictors of survival.
Rolipram, a specific type‐4 phosphodiesterase inhibitor, inhibits cyclophosphamide‐induced haemorrhagic cystitis in rats
Authors: Sakura Mizuaki , Masuda Hitoshi , Matsuoka Yoh , Yokoyama Minato , Kawakami Satoru , Kihara Kazunori 
Published: August 2008

OBJECTIVETo investigate the protective roles of type 4 phosphodiesterase (PDE4) inhibitor in cyclophosphamide (CYP)‐induced haemorrhagic cystitis, as the PDE4 inhibitor has anti‐inflammatory effects but its characterization is still unknown in urinary tract diseases.MATERIALS AND METHODSIn female Sprague‐Dawley rats, CYP was administered intraperitoneally and bladders were harvested 24 h after CYP injection. In another group, rolipram as a PDE4 inhibitor was administered before CYP treatment. The effects and mechanisms of CYP with/without rolipram pretreatment were evaluated by microscopic features, bladder wet weight, myeloperoxidase (MPO) activity, nitric oxide (NO)‐metabolite production and expression levels of inflammation‐related genes.RESULTSCYP injection resulted in severe cystitis. Pretreatment with rolipram significantly reduced the increase in bladder wet weight and MPO activity, and ameliorated histological inflammatory changes caused by CYP. The levels of inflammation‐related transcripts including inducible NO synthase (iNOS), interleukin‐1β and tumour necrosis factor‐α, induced by CYP, were down‐regulated significantly by pretreatment with rolipram. Also, rolipram reduced the NO‐metabolite production and iNOS protein expression in the immunohistochemical examination.CONCLUSIONThese results indicate that rolipram can attenuate the development of CYP‐induced cystitis in rats by suppressing cytokine production and iNOS induction. Thus, treatment with PDE4 inhibitor has potential clinical implications of the prevention of bladder inflammatory diseases.
The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy
Authors: Waldert Matthias , Remzi Mesut , Klingler Hans Christoph , Mueller Lukas , Marberger Michael 
Published: August 2008

OBJECTIVETo compare the overall, tumour‐specific, recurrence‐free, and progression‐ free survival of patients with upper urinary tract transitional cell carcinoma (UUT‐TCC) treated with laparoscopic nephroureterectomy (LNU) or standard open NU (ONU).PATIENTS AND METHODSClinical, pathological and follow‐up data were analysed for 43 LNUs and 59 ONUs performed at our institution from 1999 to 2006. In LNU the kidney was removed laparoscopically as in radical nephrectomy, but without transecting the ureter. The specimen was then removed intact with the entire ureter and a bladder cuff through a nonmuscle‐splitting supra‐inguinal incision. ONU was performed through separate intercostal and supra‐inguinal incisions with the entire specimen being removed intact with a bladder cuff through the latter.RESULTSThe mean (sd) follow‐up was 41 (20) months for LNU and 41 (29) for ONU. Pathological staging was: pTa 26% vs 20%, pT1 21% vs 27%, pT2 12% vs 17%, pT3 42% vs 34% for LNU and ONU, respectively. In all, seven vs six patients had positive nodes on final histology. Recurrent tumours in the bladder were detected in 26% of patients after LNU and in 27% after ONU after the mean follow‐up. There were no local recurrences after LNU but there was local recurrence in six patients after ONU. There were no port‐site metastases during the follow‐up. Five LNU patients and seven ONU patients developed distant or lymph node metastasis. The actuarial 5‐year tumour free‐survival rate was 79% in the LNU group vs 76% in the ONU group (P = 0.82). The actuarial disease‐specific survival at 5‐years was 85% for LNU and 80% for ONU patients (P = 0.62). The surgical approach did not influence recurrence or survival.CONCLUSIONOncological results of LNU and ONU are comparable. The lower morbidity of LNU offers advantages for the patient.
Low risk of melanoma in patients with atopic dermatitis
Authors: Synnerstad I , Fredrikson M , Ternesten‐Bratel A , Rosdahl I 
Published: August 2008

AbstractBackground  There is a possible association between atopy and cancer based on the concept of atopic diseases as a hyper‐reactive state of the immune system. Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD) are subjected to local and systemic immunosuppressives, it would be expected to find an influence of AD on the melanoma risk. There is a positive correlation between the number of naevi and melanoma risk, and children and adults with AD have fewer naevi than controls although many patients receive ultraviolet treatment.Objective  This study aims to investigate the melanoma risk in a retrospective cohort of AD patients compared with the population.Study design  6280 AD patients born 1935–1979 visited five Dermatology clinics during 1986–2004. Mean follow‐up time was 36.7 years (SD 6.9) corresponding to 230 742 person‐years at risk. The cohort file was linked to the National Cancer register.Results  Six AD patients with melanoma were identified, and the Poisson regression analysis adjusted for age group, sex and year resulted in an incidence rate ratio of 0.49 (95% confidence interval: 0.27–1.35, P = 0.08) for the AD group compared with the total population in the region.Conclusion  A low risk to develop melanoma was found in AD patients. However, the results must be interpreted with caution since the small number of expected cases of melanoma makes the risk estimate sensitive to chance effects. We hypothesize that formation of naevi and progression to melanoma is counteracted by the inflammatory process in the skin of AD patients.
The Developmental Basis of Skeletal Cell Differentiation and the Molecular Basis of Major Skeletal Defects
Authors: Blair Harry C. , Zaidi Mone , Huang Christopher L.‐H. , Sun Li 
Published: August 2008

AbstractVertebrate skeletal differentiation retains elements from simpler phyla, and reflects the differentiation of supporting tissues programmed by primary embryonic development. This developmental scheme is driven by homeotic genes expressed in sequence, with subdivision of skeletal primordia driven by a combination of seven transmembrane‐pass receptors responding to Wnt‐family signals, and by bone morphogenetic family signals that define borders of individual bones. In sea‐dwelling vertebrates, an essentially complete form of the skeleton adapted by the land‐living vertebrates develops in cartilage, based on type II collagen and hydrophilic proteoglycans. In bony fishes, this skeleton is mineralized to form a solid bony skeleton. In the land‐living vertebrates, most of the skeleton is replaced by an advanced vascular mineralized skeleton based on type I collagen, which reduces skeletal mass while facilitating use of skeletal mineral for metabolic homeostasis. Regulation of the mammalian skeleton, in this context, reflects practical adaptations to the needs for life on land that are related to ancestral developmental signals. This regulation includes central nervous system regulation that integrates bone turnover with overall metabolism. Recent work on skeletal development, in addition, demonstrates molecular mechanisms that cause developmental bone diseases.
Critical role of acrolein in secondary injury following ex vivo spinal cord trauma
Authors: Hamann Kristin , Durkes Abigail , Ouyang Hui , Uchida Koji , Pond Amber , Shi Riyi 
Published: August 2008

AbstractThe pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. To further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that (i) acrolein–Lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury by itself produces significant membrane damage and increased superoxide production; and (iii) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 h following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.
Characterization of urotensin II, distribution of urotensin II, urotensin II‐related peptide and UT receptor mRNAs in mouse: evidence of urotensin II at the neuromuscular junction
Authors: Dubessy Christophe , Cartier Dorthe , Lectez Benoît , Bucharles Christine , Chartrel Nicolas , Montero‐Hadjadje Maïté , Bizet Patrice , Chatenet David , Tostivint Hervé , Scalbert Elizabeth , Leprince Jérome , Vaudry Hubert , Jégou Sylvie , Lihrmann Isabelle 
Published: August 2008

AbstractUrotensin II (UII) and UII‐related peptide (URP) are paralog neuropeptides whose existence and distribution in mouse have not yet been investigated. In this study, we showed by HPLC/RIA analysis that the UII‐immunoreactive molecule in the mouse brain corresponds to a new UII17 isoform. Moreover, calcium mobilization assays indicated that UII17 and URP were equally potent in stimulating UII receptor (UT receptor). Quantitative RT‐PCR and in situ hybridization analysis revealed that in the CNS UII and URP mRNAs were predominantly expressed in brainstem and spinal motoneurons. Besides, they were differentially expressed in the medial vestibular nucleus, locus coeruleus and the ventral medulla. In periphery, both mRNAs were expressed in skeletal muscle, testis, vagina, stomach, and gall bladder, whereas only URP mRNA could be detected in the seminal vesicle, heart, colon, and thymus. By contrast, the UT receptor mRNA was widely expressed, and notably, very high amounts of transcript occurred in skeletal muscle and prostate. In the biceps femoris muscle, UII‐like immunoreactivity was shown to coexist with synaptophysin in muscle motor end plate regions. Altogether these results suggest that (i) UII and URP may have many redundant biological effects, especially at the neuromuscular junction; (ii) URP may more specifically participate to autonomic, cardiovascular and reproductive functions.
Involvement of miltefosine‐mediated ERK activation in glioma cell apoptosis through Fas regulation
Authors: Tewari Richa , Sharma Vivek , Koul Nitin , Sen Ellora 
Published: August 2008

AbstractThe anti‐neoplastic property of alkyl phospholipids has been tested for the treatment of several malignancies. In this study, we evaluated the efficacy of miltefosine (Hexadecylphosphocholine – an alkyl phospholipids analogue) on glioblastoma multiforme. In this study, we demonstrate that miltefosine‐induced apoptosis is accompanied by elevated Fas, Fas‐associated death domain (FADD) expression, caspase‐8 activity and the increased distribution of Fas and FADD towards lipid raft microdomain to form death inducing signaling complex. Treatment with miltefosine resulted in increase in Ras, extracellular signal‐regulated kinase (ERK) and p38MAPK activity. Expression of dominant‐negative Ras (Ras N17) attenuated miltefosine‐mediated apoptosis. Although inhibition of both ERK and p38MAPK decreased the pro‐apoptotic effects of miltefosine, it was the inhibition of ERK and not p38MAPK activation that decreased Fas and FADD expression. An ERK‐dependent increase in the expression of γH2AX‐involved in response to DNA double‐stranded breaks was also observed. Taken together, our findings suggest the involvement of ERK activation in miltefosine‐induced glioma cell apoptosis.
Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum
Authors: Whittaker Matthew T. , Gibbs Terrell T. , Farb David H. 
Published: August 2008

AbstractNeuromodulators that alter the balance between lower‐frequency glutamate‐mediated excitatory and higher‐frequency GABA‐mediated inhibitory synaptic transmission are likely to participate in core mechanisms for CNS function and may contribute to the pathophysiology of neurological disorders such as schizophrenia and Alzheimer’s disease. Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABAAreceptor mediated synaptic transmission. The enzymes necessary for PS synthesis and degradation are found in brain tissue of several species including human and rat, and up to 5 nM PS has been detected in extracts of postmortem human brain. Here, we ask whether PS could modulate transmitter release from nerve terminals located in the striatum. Superfusion of a preparation of striatal nerve terminals comprised of mixed synaptosomes and synaptoneurosomes with brief‐duration (2 min) pulses of 25 nM PS demonstrates that PS increases the release of newly accumulated [3H]dopamine ([3H]DA), but not [14C]glutamate or [3H]GABA, whereas pregnenolone is without effect. PS does not affect dopamine transporter (DAT) mediated uptake of [3H]DA, demonstrating that it specifically affects the transmitter release mechanism. The PS‐induced [3H]DA release occurs via an NMDA receptor (NMDAR) dependent mechanism as it is blocked by D‐2‐amino‐5‐phosphonovaleric acid. PS modulates DA release with very high potency, significantly increasing [3H]DA release at PS concentrations as low as 25 pM. This first report of a selective direct enhancement of synaptosomal dopamine release by PS at picomolar concentrations via an NMDAR dependent mechanism raises the possibility that dopaminergic axon terminals may be a site of action for this neurosteroid.
Spatial and temporal patterns of bone formation in ectopically pre‐fabricated, autologous cell‐based engineered bone flaps in rabbits
Authors: Scheufler Oliver , Schaefer Dirk J. , Jaquiery Claude , Braccini Alessandra , Wendt David J. , Gasser Jürg A. , Galli Raffaele , Pierer Gerhard , Heberer Michael , Martin Ivan 
Published: August 2008

AbstractBiological substitutes for autologous bone flaps could be generated by combining flap pre‐fabrication and bone tissue engineering concepts. Here, we investigated the pattern of neotissue formation within large pre‐fabricated engineered bone flaps in rabbits. Bone marrow stromal cells from 12 New Zealand White rabbits were expanded and uniformly seeded in porous hydroxyapatite scaffolds (tapered cylinders, 10–20 mm diameter, 30 mm height) using a perfusion bioreactor. Autologous cell‐scaffold constructs were wrapped in a panniculus carnosus flap, covered by a semipermeable membrane and ectopically implanted. Histological analysis, substantiated by magnetic resonance imaging (MRI) and micro‐computerized tomography scans, indicated three distinct zones: an outer one, including bone tissue; a middle zone, formed by fibrous connective tissue; and a central zone, essentially necrotic. The depths of connective tissue and of bone ingrowth were consistent at different construct diameters and significantly increased from respectively 3.1 ± 0.7 mm and 1.0 ± 0.4 mm at 8 weeks to 3.7± 0.6 mm and 1.4 ± 0.6 mm at 12 weeks. Bone formation was found at a maximum depth of 1.8 mm after 12 weeks. Our findings indicate the feasibility of ectopic pre‐fabrication of large cell‐based engineered bone flaps and prompt for the implementation of strategies to improve construct vascularization, in order to possibly accelerate bone formation towards the core of the grafts.
Endoluminal Norepinephrine Inhibits Smooth Muscle Activity of the Pig Pyeloureter by Stimulation of β‐Adrenoceptors without Side Effects
Authors: Mortensen Jens , Holst Uffe , Jakobsen Jørn Skibsted , Andreasen Frederik 
Published: August 2008

Abstract:  It has been demonstrated in pigs that endoluminal administration of norepinephrine reduces the increase in renal pelvic pressure during perfusion. The purposes were to describe concentration–response relationship and receptor mechanism of the effect of norepinephrine on muscle function of pyeloureter and to reveal possible side effects on cardiovascular and renal functions. Renal pelvis was perfused, while pelvic pressure, cardiovascular and renal functional parameters were recorded. In group A, a pelvic pressure increase was examined during pressure flow studies with norepinephrine solutions (0, 1, 5, 50 and 100 µg/ml). In group B, pelvis was perfused with 6 ml/min. norepinephrine solutions (0, 0.001, 0.01, 0.1 and 1 µg/ml). In group C, pelvis was perfused with 6 ml/min. norepinephrine, norepinephrine + sotalol 10−6 mol/l and norepinephrine + phentolamine 10−6 mol/l. Norepinephrine solutions of 0, 10−8, 10−7, 10−6, 10−5 and 10−4 mol/l were used. In group A, all norepinephrine solutions lowered the pelvic pressure increase significantly. Large increases in plasma and urine norepinephrine occurred with 50 and 100 µg/ml, but cardiovascular and renal functions remained unchanged. In group B, a significant diminishing pelvic pressure increase with all solutions was seen with a significant difference between all solutions. In group C, norepinephrine demonstrated a concentration–response curve with EC50 between 10−8 and 10−7 mol/l (10−7.27±0.40). Sotalol had a smooth muscle inhibitory effect on the pyeloureter and inhibited the effect of norepinephrine increasing EC50 by about a factor 10 (10−6.40±1.17). No convincing effect of phentolamine was observed. Endoluminal norepinephrine probably stimulates β‐adrenoceptors and inhibits a renal pelvis pressure increase to perfusion in a dose‐related way without side effects. Endoluminal norepinephrine is safe in pigs and may be useful under endoscopy of the pyeloureter.
Physiologically Motivated Time‐Delay Model to Account for Mechanisms Underlying Enterohepatic Circulation of Piroxicam in Human Beings
Authors: Tvrdonova Martina , Dedik Ladislav , Mircioiu Constantin , Miklovicova Daniela , Durisova Maria 
Published: August 2008

Abstract:  The study was conducted to formulate a physiologically motivated time‐delay (PM TD) mathematical model for human beings, which incorporates disintegration of a drug formulation, dissolution, discontinuous gastric emptying and enterohepatic circulation (EHC) of a drug. Piroxicam, administered to 24 European, healthy individuals in 20 mg capsules Feldene® Pfizer, was used as a model drug. Plasma was analysed for piroxicam by a validated high‐performance liquid chromatography method. The PM TD mathematical model was developed using measured plasma piroxicam concentration‐time profiles of the individuals and tools of a computationally efficient mathematical analysis and modeling, based on the theory of linear dynamic systems. The constructed model was capable of (i) quantifying different fractions of the piroxicam dose sequentially disposable for absorption and (ii) estimating time delays between time when the piroxicam dose reaches stomach and time when individual of fractions of the piroxicam dose is disposable for absorption. The model verification was performed through a formal proof, based on comparisons of observed and model‐predicted plasma piroxicam concentration‐time profiles. The model verification showed an adequate model performance and agreement between the compared profiles. Accordingly, it confirmed that the developed model was an appropriate representative of the piroxicam fate in the individuals enrolled. The presented model provides valuable information on factors that control dynamic mechanisms of EHC, that is, information unobtainable with the models proposed for the EHC analysis previously.