bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of attenuated neuronal nitric‐oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits
Authors: Numao Noboru , Masuda Hitoshi , Sakai Yasuyuki , Okada Youhei , Kihara Kazunori , Azuma Hiroshi 
Published: April 2007

OBJECTIVETo investigate whether changes in neuronal nitric oxide synthase (nNOS) protein expression and arginase activity are implicated in impairing the neurogenic cavernosal relaxation in aged rabbits, as NO is important in the neurogenic relaxation of corpus cavernosum during the erectile state.MATERIALS AND METHODSCavernosal specimens of young adult (3–6 months old) and aged (36–48 months old) rabbits were used for isometric tension experiments, Western blot analysis, cGMP determination and measurements of NOS and arginase activities.RESULTSThe neurogenic relaxation and cGMP production in response to electrical‐field stimulation were significantly impaired in aged cavernosal specimens. Western blot analysis showed that nNOS protein was highly expressed in cavernosal specimens from young rabbits, but was undetectable or greatly decreased in old rabbits, with no change in overall NOS activity. Arginase activity in aged cavernosal specimens was significantly higher than in young rabbits. Supplementing with excess l‐arginine, or giving S‐(2‐boronoethyl)‐l‐cysteine as an arginase inhibitor, significantly increased the neurogenic relaxation at lower frequencies only in the younger rabbits.CONCLUSIONThese results suggest that impairment of neurogenic and NO‐mediated relaxation in the aged corpus cavernosum possibly results from the down‐regulation of nNOS protein. The reduced l‐arginine bioavailability to nNOS due to accelerated arginase activity would lead to further impairment of neurogenic NO production, in concert with decreased nNOS protein expression.
Does the molecular staging in pelvic lymph nodes improve the detection of relevant prostate cancer metastases? An assessment after 6 years
Authors: Schostak Martin , Krause Hans , Miller Kurt , Schrader Mark , Kempkensteffen Carsten , Kollermann Jens 
Published: April 2007

OBJECTIVETo assess the course of cancer‐free survival and thus determine how reliably reverse transcriptase‐polymerase chain reaction (RT‐PCR) can detect prostate‐specific antigen (PSA)‐expressing cells, as patients with untreated lymph node‐positive prostate cancer tend to have a poor prognosis, whereas those treated with radical prostatectomy (RP) and immediate adjuvant hormonal therapy show excellent local disease control and a disease‐free survival comparable with that of patients with negative lymph nodes, but the detection of micrometastatic disease in pelvic lymph nodes remains a major challenge.PATIENTS AND METHODSQuantitative RT‐PCR was used to detect PSA mRNA expression in total RNA of 457 pelvic lymph nodes from 70 patients who had RP (53 patients) or laparoscopic lymphadenectomy (17) at our clinic in 1999/2000. For this purpose, alternate sections of lymph node tissue were either snap‐frozen for later RNA isolation or examined by standard histopathological methods. Clinicopathological data, adjuvant treatments and follow‐up data were recorded for all patients.RESULTSAfter January 2006 (6‐year observation period), 13 patients had no follow‐up data, while 27 had biochemical (PSA) recurrence or other evidence of clinical progression (two died from prostate cancer), and 30 had no signs of recurrence. Compared to the ‘reference’ standard (histopathology), the PCR method had a sensitivity of 83% and a specificity of 66%. The method had a positive predictive value of 52% and a negative predictive value of 57%.CONCLUSIONConsidered alone, pelvic lymph node PSA RT‐PCR does not predict the clinical course better than a histopathological assessment of lymph nodes. However, it also identifies some patients with negative histology who later show progression. When added to the pathological classification, PSA RT‐PCR improves the detection rate of primary lymphatic dissemination.
Molecular characterization of M2 and M3 muscarinic receptor expression in bladder from women with refractory idiopathic detrusor overactivity
Authors: Mansfield Kylie J. , Liu Lu , Moore Kate H. , Vaux Kenneth J. , Millard Richard J. , Burcher Elizabeth 
Published: April 2007

In a study from Sydney, authors present data on the expression of M2 and M3 receptors in human detrusor and bladder mucosa, comparing patients with idiopathic detrusor overactivity with controls. It was found that M3 muscarinic receptor RNA expression was reduced in mucosa from patients with detrusor overactivity, leading to a proposal that mucosal M3 receptors might have an important role in the aetiology of this condition.OBJECTIVETo examine the expression of muscarinic M2 and M3 receptors in human bladder detrusor and mucosa, from controls and patients with idiopathic detrusor overactivity (IDO), as antimuscarinic agents are the primary pharmacological treatment for IDO.PATIENTS AND METHODSBiopsies from the bladder body were collected at cystoscopy from 20 women with urodynamically confirmed refractory IDO (age range 25–86 years); biopsies were also collected from 30 asymptomatic female controls (age range 32–87 years). Samples were collected into RNA extraction medium and dissected into mucosa (urothelium plus lamina propria) and detrusor. RNA was extracted and the expression of M2 and M3 receptor mRNA determined by quantitative competitive reverse transcription‐polymerase chain reaction. Results were normalized to β‐actin expression in the same sample.RESULTSExpression of M3 receptor mRNA, in mucosa of IDO patients (median 0.057 pg M3/100 ng total RNA; interquartile range 0.03–0.13, 12 samples), was four times (P = 0.039, Mann–Whitney) lower than from the control (median 0.22 pg M3/100 ng total RNA; 0.13–0.51, 11 samples). The expression of muscarinic M3 receptor mRNA was higher (14–35 times) in detrusor (control median 3.17; 26 samples) than in mucosa and did not change in IDO (median 2.03; 14 samples). M2 expression was not significantly different with region or with IDO.CONCLUSIONSThese data show that M3 muscarinic receptor mRNA expression was significantly less in mucosa from IDO patients than from age‐matched controls. The role of mucosal M3 receptors is unknown at present and elucidation of this role might provide a greater understanding of the aetiology of IDO.
Antiviral activity of low‐dose alovudine in antiretroviral‐experienced patients: results from a 4‐week randomized, double‐blind, placebo‐controlled dose‐ranging trial*
Authors: Ghosn J , Quinson A‐M , Sabo ND , Cotte L , Piketty C , Dorléacq N , Bravo M‐L , Mayers D , Harmenberg J , Mårdh G , Valdez H , Katlama C 
Published: April 2007

BackgroundAlovudine inhibits replication of highly nucleoside reverse transcriptase inhibitor (NRTI)‐resistant HIV strains in vitro. However, dose‐dependent safety concerns resulted in its initial development being halted. Recently, a 4‐week course of alovudine 7.5 mg/day added to a stavudine‐free failing regimen yielded a significant decrease in viral load by −1.88 log10 HIV‐1 RNA copies/mL. The magnitude of the reduction in viral load suggested that lower doses might still be effective while offering adequate safety during long‐term use.ObjectiveTo determine whether lower dosages of alovudine still provide significant antiviral activity in patients with broad NRTI resistance.MethodsA randomized, double‐blind, placebo‐controlled trial investigating three doses of alovudine (0.5, 1 and 2 mg) or placebo added for 4 weeks to a failing regimen in patients with evidence of NRTI‐resistant HIV strains [≥2 thymidine‐associated mutations (TAMs)]. The primary endpoint was the mean viral load reduction between baseline and week 4.Results
Seventy‐two patients were enrolled in the study: 21, 13, 18 and 20 in the placebo and 0.5, 1 and 2 mg arms, respectively. Baseline median CD4 count and viral load were 298 cells/μL (range 44–692 cells/μL) and 3.9 log10 copies/mL (range 2.5–5.2 log10 copies/mL), respectively. Baseline viral isolates harboured a median of four TAMs. Alovudine was added to a median four‐drug failing regimen. At week 4, compared with placebo, mean viral load changes were −0.42 log10 [95% confidence interval (CI) −0.67 to −0.18] and −0.30 log10 (−0.55 to −0.06) in the 2 and 1 mg arms, respectively. There was no significant change in CD4 cell count. Alovudine was well tolerated.Conclusion:A 4‐week course of alovudine 2 mg/day provided a modest but significant viral load reduction in patients harbouring viruses with a median of four TAMs.
Long‐term evolution of CD4 count in patients with a plasma HIV RNA persistently <500 copies/mL during treatment with antiretroviral drugs
Authors: Le Moing V , Thiébaut R , Chêne G , Sobel A , Massip P , Collin F , Meyohas MC , Al Kaïed F , Leport C , Raffi F ,   the ANRS CO8 (APROCO/COPILOTE) Study Group
Published: April 2007

BackgroundThe increase in CD4 count may reach a plateau after some duration of virological response to highly active antiretroviral therapy (HAART).MethodsA total of 1281 HIV‐infected patients initiating HAART were enrolled in the AntiPROtease (APROCO) cohort. We investigated determinants of increase in CD4 count using longitudinal mixed models in patients who maintained a plasma HIV RNA <500 HIV‐1 RNA copies/mL.ResultsA total of 870 patients had a virological response at month 4. The median follow‐up time was 57 months. Mean estimated increases in CD4 count in patients with persistent virological response were 29.9 cells/μL/month before month 4, 6.4 cells/μL/month between months 4 and 36, and 0.7 cells/μL/month (not significantly different from 0) after month 36. Three factors were associated with a significantly positive CD4 count slope after month 36: male gender (+0.9), no history of antiretroviral therapy at baseline (+1.7) and baseline CD4 count <100 cells/μL (+2.6). In patients who maintained a virological response after 5 years of HAART, a CD4 count >500 cells/μL was achieved in 83% of those with a baseline CD4 count ≥200 cells/μL and in 45% of those with a baseline CD4 count <200 cells/μL.ConclusionThe increase in CD4 count reaches a plateau after 3 years of virological response. Even if patients initiating HAART with low CD4 counts still show a CD4 count increase after 3 years, it remains insufficient to overcome immune deficiency in all patients.
Combination antiretroviral therapy without a nucleoside reverse transcriptase inhibitor: experience from 334 patients in three cohorts
Authors: Calmy A , Petoumenos K , Lewden C , Law M , Bocquentin F , Hesse K , Cooper D , Carr A , Bonnet F ,   for the Aquitaine Cohort, Australian HIV Observational Database and St Vincent's Hospital Cohort study groups
Published: April 2007

BackgroundToxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI.Method and patients
We analysed NRTI‐sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs.ResultsA total of 334 (3.9%) of 8477 patients were included in the present study for a median follow‐up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/μL (interquartile range 164–446 cells/μL) and 25% of patients had plasma HIV RNA below 500 HIV‐1 RNA copies/mL. In intent‐to‐treat analysis, 64% of patients had HIV RNA <500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/μL (95% confidence interval 41–76 cells/μL) at 6 months and 111 cells/μL (95% confidence interval 82–140 cells/μL) at 24 months. Prognostic factors for having HIV RNA <500 copies/mL at 6 months included independently having undetectable HIV RNA at baseline and being naïve for NNRTIs. The proportion of patients with triglycerides >2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P‐trend=0.002), and those with total cholesterol >6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P‐trend <0.001), with an increased risk for patients treated with NNRTI+PIs. Forty‐one per cent of patients discontinued their NRTI‐sparing regimen.ConclusionIn these antiretroviral‐experienced patients, NRTI‐sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.
Improved virological response to highly active antiretroviral therapy in HIV‐1‐infected patients carrying the CCR5 Δ32 deletion
Authors: Laurichesse JJ , Persoz A , Theodorou I , Rouzioux C , Delfraissy JF , Meyer L 
Published: April 2007

BackgroundPatients heterozygous for the C‐C chemokine receptor 5 (CCR5) Δ32 deletion spontaneously progress less rapidly to AIDS and death than do wild‐type patients. We investigated whether the CCR5 Δ32 deletion has an impact on immunological, virological and clinical responses to highly active antiretroviral therapy (HAART) in HIV‐1‐infected patients.Patients and methodsWe included in the study 565 HIV‐1‐infected patients from the French HIV‐1 infected cohort with documented date of serconversion (SEROCO)/haemophiliacs HIV‐1 infected (HEMOCO) cohorts, who started HAART after 1996. We investigated virological responses to HAART at 6 months (defined as a plasma HIV‐1 RNA measurement below the threshold of detection or a 2 log HIV‐1 RNA decrease) and at 12 months (defined as a plasma HIV‐1 RNA measurement below the threshold of detection) and clinical response to HAART by Kaplan–Meier survival curves, with AIDS and death as outcomes.ResultsThe Δ32 heterozygous patients (n=83; 15%) had a better virological response to HAART than wild‐type patients (73 vs 53% at 6 months, P=0.01; and 60 vs 44% at 12 months, P=0.01). This better virological response was still observed after adjustment for antiretroviral status (whether or not patients were naïve to antiretroviral therapy), year of HAART initiation, number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients and wild‐type patients in terms of survival and AIDS‐free survival.ConclusionsCCR5 Δ32 heterozygous patients were more likely to have a virological response to HAART than wild‐type patients at 6 and 12 months. However, this virological response did not produce better immunological and clinical responses. The long‐term impact of the Δ32 deletion on survival in HIV‐1‐infected treated patients should be investigated in a meta‐analysis.
Concomitant use of gastric acid‐reducing agents is frequent among HIV‐1‐infected patients receiving protease inhibitor‐based highly active antiretroviral therapy*
Authors: Van Lunzen J , Liess H , Arastéh K , Walli R , Daut B , Schürmann D 
Published: April 2007

ObjectiveThe aim of the study was to assess the frequency of the concurrent use of gastric acid‐reducing agents among HIV‐1‐infected patients treated with highly active antiretroviral therapy (HAART) combinations.MethodsAn anonymous, semistructured, self‐administered questionnaire was consecutively distributed among HIV‐1‐infected patients at routine visits to specialized HIV clinics. The questionnaire contained 17 items asking specifically for information on current antiretroviral treatments and the use of gastric acid‐reducing agents as well as demographic data.ResultsA total of 424 patients in 12 centres participated in the study: 85% were male, 88% were of German nationality, 82% were >35 years of age and 201 (47.4%) were receiving a protease inhibitor (PI)‐containing HAART regimen. Of these, 74 (37%) had received an acid‐reducing drug within the previous 6 months and 43 (58%) were currently still on it. Two‐thirds of patients (64.9%) were treated with proton‐pump inhibitors (pantoprazole, omeprazole or esomeprazole) and 56% of patients on PI‐containing regimens had been taking these drugs for longer than 2 months and up to a maximum of 3 years. The majority of patients (77%) had received the prescription for the acid‐reducing drugs from their HIV specialist and the remaining patients had received over the counter (OTC) medication or prescriptions from other medical personnel.ConclusionsA substantial subset of patients treated with HAART combinations, including those on PI‐containing regimens, were using concomitant acid‐reducing drugs, most often proton‐pump inhibitors. As negative drug–drug interactions between some of the (boosted) PIs and gastric acid‐reducing agents have recently been reported, HIV physicians should take this into account when prescribing PI‐containing HAART combinations in order to avoid an additional risk of treatment failure.
Relative antiviral efficacy of ritonavir‐boosted darunavir and ritonavir‐boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials
Authors: Hill A , Moyle G 
Published: April 2007

ObjectiveTo compare the relative antiviral efficacy of TMC114 with low‐dose ritonavir (TMC114/r) and tipranavir with low‐dose ritonavir (TPV/r) vs. control protease inhibitor (CPI) in treatment‐experienced patients, using data from the POWER 1/2 and RESIST 1/2 trials. These trials recruited antiretroviral‐experienced patients with HIV RNA > 1000 HIV‐1 RNA copies/mL and at least one primary PI mutation, and used optimized nucleoside reverse transcriptase inhibitors with or without enfuvirtide, plus investigator‐selected CPI in the control arms.MethodsFor the POWER trials, data from the 600/100 mg twice a day (bid) dose and CPI arms (n=201) were included, while all data from the RESIST trials (TPV/r 500/200 mg bid and CPI; n=1159) were included. The difference in week 24 efficacy (intent to treat) for the new PI vs. CPI was compared between the trials.ResultsOverall baseline characteristics were well matched across the trials. At week 24, 72% of TMC114/r patients achieved a ≥1 log10 copies/mL reduction in HIV RNA compared with 40% of TPV/r patients (for CPI patients, this percentage was 21 and 18%, respectively, in the POWER and RESIST trials). The treatment benefit of TMC114/r over CPI in the POWER trials was greater (outside the 95% confidence intervals) than the benefit of TPV/r over CPI in the RESIST trials, for the 24‐week HIV RNA endpoints of 1 log10 copies/mL reduction, <400 copies/mL and <50 copies/mL, and also for the mean rise in CD4 count. In sensitivity analysis, this difference in efficacy was strongest for those who did not also use enfuvirtide.ConclusionsGiven the caveats of this type of analysis (for example, possible differences in trial conduct, and undetected differences in baseline resistance profiles), the efficacy benefits of TMC114/r vs. CPI in the POWER trials appear to be greater than the benefits of TPV/r vs. CPI in the RESIST trials, for patients who did not also use enfuvirtide.
Hybrid finite element–finite volume discretization of complex geologic structures and a new simulation workflow demonstrated on fractured rocks
Authors: PALUSZNY A. , MATTHÄI S. K. , HOHMEYER M. 
Published: April 2007

AbstractThe generation of computational meshes of complex geological objects is a challenge: their shape needs to be retained, resolution has to adapt to local detail, and variations of material properties in the objects have to be represented. Also mesh refinement and adaptation must be sufficient to resolve variations in the computed variable(s). Here, we present an unstructured hybrid finite element, node‐centred finite‐volume discretization suitable for solving fluid flow, reactive transport, and mechanical partial differential equations on a complex geometry with inhomogeneous material domains. We show that resulting meshes accurately capture free‐form material interfaces as defined by non‐uniform rational B‐spline curves and surfaces. The mesh discretization error is analysed for the elliptic pressure equation and an error metric is introduced to guide mesh refinement. Finite elements and finite volumes are represented in parametric space and integrations are conducted numerically. Subsequently, integral properties are mapped to physical space using Jacobian transformations. This method even retains its validity when the mesh is deformed. The resulting generic formulation is demonstrated for a transport calculation performed on a complex discrete fracture model.
Predicting occurrence of wolf territories in Scandinavia
Authors: Karlsson J. , Brøseth H. , Sand H. , Andrén H. 
Published: April 2007

AbstractWe used logistic regression to compare a set of habitat features inside known Scandinavian wolf Canis lupus territories with the same habitat features in areas outside known territories, but still close enough to be available for wolf colonization. In addition, we analysed changes in habitat variables over time within wolf territories. Wolf territories had lower densities of roads, built‐up areas and open land than areas outside wolf territories, but there was no difference in the density of the wolves' main prey, elk Alces alces. The logistic regression model classified 79% of Scandinavia outside the reindeer husbandry area as suitable wolf habitat, that is with a probability of wolf occurrence >0.5. The proportion of built‐up areas within the wolf territory decreased as the ‘borders’ of the wolf territory changed over time. Our model had a reasonably high predictive power, with correct classification in 90% (18 of 20) of the observed wolf territories in the study area. Polygons, randomly distributed outside the observed wolf territories, were correctly classified as not being occupied by wolves in 85% of the cases (17 of 20). This allows a more effective use of resources to, for example, prevent wolf depredation on livestock and dogs.
Cell number and cellular composition in vermiform larvae of dicyemid mesozoans
Authors: Furuya H. , Hochberg F. G. , Tsuneki K. 
Published: April 2007

AbstractCell numbers and cellular composition were examined in vermiform larvae of 44 species of dicyemid mesozoans phylum Dicyemida belonging to six genera: Conocyema, Dicyema, Dicyemennea, Dicyemodeca, Microcyema and Pseudicyema. In addition, the literature on vermiform larvae of another 59 species was reviewed. Vermiform larvae typically have a constant number of peripheral cells that are species specific. Interspecific variations in the total number of peripheral cells range from 10 to 39. The most frequent number is either 22 or 23. Differences in the total number of peripheral cells are mostly due to differences in the number of trunk peripheral cells, such as parapolar cells, diapolar cells and uropolar cells. The body length of vermiform larvae is positively correlated with the number of trunk peripheral cells. Interspecific variations in the total number of trunk peripheral cells range from 2 to 31. The most frequent number is 14. In species with 14 trunk peripheral cells, individual variations of cell numbers were minimal. In species with more trunk peripheral cells, some individual variations appeared. Increase and decrease of trunk cell number might cause diversity of dicyemids, which is possibly related to speciation in these simple multicellular animals.