bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Impairment in Women Undergoing Laparoscopic Surgery for Genital Prolapse: A Hospital-Based Cohort Study
Authors: Banerjee Carolin , Sachse Katrin , Hellmich Martin , Fanselau Christian , Banerjee Marc , Noé Günter Karl
Published: December 2010

Introduction: No data regarding sexuality following laparoscopic prolapse surgery are available to date. Our hypothesis is that laparoscopic sacropexy does not influence sexuality negatively, whereas concomitant (vaginal) surgery negatively influences sexuality. Methods: Participants were 132 patients who underwent laparoscopic sacropexy. We compared pre- and postoperative sexual scores by 2 validated questionnaires. Results: The response rate was 84% (111/132). No change in sexual activity was reported after surgery. In the sexually active group (56.8%; 63/111) the impairment of sexuality was significantly reduced in all age groups independently of concomitant vaginal surgery. In the sexually inactive group, only 4.3% (2/48) were inactive because of vaginal symptoms before operation. After the operation these patients stayed inactive; however, 1 reported reasons unrelated to prolapse. Conclusions: Laparoscopic prolapse surgery reduces sexual impairment in sexually active patients. There appears to be no benefit for patients who are not sexually active for reasons related to the prolapse. Concomitant surgery does not affect sexual activity.
Phase II Study of the Human Anti-Epithelial Cell Adhesion Molecule Antibody Adecatumumab in Prostate Cancer Patients with Increasing Serum Levels of Prostate-Specific Antigen after Radical Prostatectomy
Authors: Marschner Norbert , Rüttinger Dominik , Zugmaier Gerhard , Nemere Gyula , Lehmann Jan , Obrist Peter , Baeuerle Patrick A. , Wolf Andreas , Schmidt Margit , Abrahamsson Per-Anders , Reinhardt Carsten , Heidenreich Axel
Published: December 2010

Background: Rising serum levels of prostate-specific antigen (PSA) after radical prostatectomy are indicative of recurrent prostate cancer. This double-blind, placebo-controlled phase II study evaluated the anti-tumour activity of the anti-epithelial cell adhesion molecule (EpCAM) antibody adecatumumab in delaying biochemical disease progression. Patients and Methods: Prostate cancer patients with increasing serum PSA levels following radical prostatectomy were randomized to low- (2 mg/kg) or high-dose adecatumumab (6 mg/kg) or placebo. The primary efficacy endpoint was the mean change from baseline in total serum PSA at week 24. Secondary endpoints included PSA response rate, prolongation of serum PSA doubling time and time to biochemical disease progression. Results: The primary and secondary endpoints of the study were not met in the predefined analyses. In a retrospective analysis of patients with baseline PSA ≤1 ng/ml and a high EpCAM expression, both the mean increase in PSA from baseline to week 24 and the PSA doubling time at week 15 were significantly improved in the high-dose adecatumumab group compared with the placebo group. Most frequent treatment-related clinical adverse events were gastrointestinal (diarrhoea and nausea) or general events (chills), showing a dose dependency but no grade 3/4 intensity in any patient. Conclusion: In men with rising PSA levels after radical prostatectomy and no evidence of clinical relapse, adecatumumab delayed disease progression in a subgroup of patients with baseline PSA levels ≤1 ng/ml and high EpCAM-expressing tumours.
Tolerability of Aztreonam in Patients with Cell-Mediated Allergy to β-Lactams
Authors: Buonomo A. , Nucera E. , De Pasquale T. , Pecora V. , Lombardo C. , Sabato V. , Colagiovanni A. , Rizzi A. , Aruanno A. , Pascolini L. , Patriarca G. , Schiavino D.
Published: December 2010

Background: Cross-reactivity between aztreonam and β-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to β-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other β-lactams and its tolerability in patients with cell-mediated allergy to these drugs. Methods: We studied 78 patients with cell-mediated allergy to β-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. Results: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 β-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. Conclusions: Our data confirm the lack of cross-reactivity between β-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in β-lactam-allergic patients.
Simultaneous Stimulation with TGF-β1 and TNF-α Induces Epithelial Mesenchymal Transition in Bronchial Epithelial Cells
Authors: Kamitani Sumiko , Yamauchi Yasuhiro , Kawasaki Shin , Takami Kazutaka , Takizawa Hajime , Nagase Takahide , Kohyama Tadashi
Published: December 2010

Background: Airway remodeling is an important feature of chronic airway disease, but the mechanisms involved remain unclear. Recently, epithelial mesenchymal transition (EMT) was reported to be associated with tissue fibrosis. TGF-β1, which is a potent inducer of EMT, is thought to be related to the pathogenesis of airway remodeling. We investigated whether TGF-β1 and/or TNF-α induce EMT in bronchial epithelial cells. Methods: Cultured BEAS-2B cells and primary normal human bronchial epithelial cells (NHBE) were treated with TGF-β1 and/or TNF-α. Morphological changes and the expression of EMT-related markers were evaluated by immunocytochemical staining. Expressions of EMT-related markers, extracellular matrix (ECM) components (collagen type I and versican), and TGF-β receptors I, II, and III were analyzed by quantitative RT-PCR. Migration was evaluated using the Boyden chamber technique. Results: The TGF-β1-induced EMT in BEAS-2B cells was demonstrated on the basis of morphological changes and the downregulation of E-cadherin. Costimulation with TNF-α enhanced the TGF-β1-induced morphological changes and increased vimentin expression. Treatment with TGF-β1 increased the expression of collagen type I and versican. EMT induced with TGF-β1 plus TNF-α promoted cell migration. Stimulation of NHBE with TGF-β1 led to EMT. Conclusion: TGF-β1 induced EMT in BEAS-2B cells, and costimulation with TNF-α enhanced the EMT. As a result of the EMT process, BEAS-2B cells acquired functions of mesenchymal cells. In addition, TGF-β1 treatment induced EMT in NHBE as shown by changes in EMT-related markers. Bronchial epithelial cells might contribute to airway remodeling through EMT.
Chromophobe Renal Cell Carcinoma with Osteosarcoma Differentiation: Case Report and Literature Review
Authors: Li Yao-Feng , Cha Tai-Lung , Jin Jong-Shiaw , Yu Cheng-Ping
Published: December 2010

Chromophobe renal cell carcinoma is a distinct subtype of renal cell carcinoma that is well known for its relatively good prognosis. When it presents with sarcomatoid differentiation, necrosis of the sarcomatoid area or angiolymphatic invasion, it becomes a highly aggressive neoplasm. The presence of osteosarcoma-like elements in sarcomatoid chromophobe renal cell carcinoma is very rare as only 5 cases have been reported previously. We present a 6th case of sarcomatoid chromophobe renal cell carcinoma, which had an osteosarcoma differentiation component. However, the correlation between the presence of heterologous elements and prognosis is unknown because of the rarity of this phenomenon.
Novel Ribbon-Type Nuclear Factor of Activated T Cells Decoy Oligodeoxynucleotides Preclude Airways Hyperreactivity and Th2 Cytokine Expression in Experimental Asthma
Authors: Nakamura Yutaka , Nagashima Hiromi , Akiyama Masachika , Sato Atsuko , Miyamoto Takayuki , Sasaki Nobuhito , Nitanai Hiroo , Kowata Koko , Nakadate Toshihide , Kobayashi Hitoshi , Uesugi Noriyuki , Sugai Tamotsu , Kakiuchi Terutaka , Inoue Hiroshi , Yamauchi Kohei
Published: December 2010

Background: Nuclear factor of activated T cells (NFAT) is required for the differentiation of Th2 responses, so we examined its role in mouse experimental asthma and tested the hypothesis that an NFAT blockade with a decoy against NFAT can prevent asthma progression. Objective: To determine the effects of the NFAT decoy oligodeoxynucleotides (ODNs) on the development of airway inflammation, we designed a novel ribbon-type ODN containing two binding sites for NFAT in a single decoy molecule without an open end, which is more stable than a conventional decoy, and largely preserved its structural integrity in the presence of nucleases. Methods: Ribbon-type NFAT decoy ODNs were transfected into ovalbumin (OVA)-sensitized CD3+ T cells in vitro. OVA-immunized mice received these cells by intraperitoneal injection. Airway hyperreactivity (AHR) was measured and the transfected CD3+ T cells’ responses to the airways were characterized. Results: Development of AHR after OVA challenge was effectively abolished after adoptive transfer of ribbon-type NFAT decoy ODN transfected CD3+ T cells. Transfer of ribbon-type decoy significantly reduced the number of inflammatory cells and the concentrations of IL-4, IL-5 and IL-13, but not IFN-γ, in the bronchoalveolar lavage of the recipient mice. Conclusion: These results suggest the inhibitory effect of ribbon-type decoy ODNs against NFAT on the induction of bronchial asthma. Adoptively transferred CD3+ T cells, which are transfected with NFAT decoy, may be an effective strategy for the treatment of asthma.
Investigative Clinical Study on Prostate Cancer Part III: Exploring Total PSA and Free Testosterone Distributions and Linear Correlations in Groups and Subgroups of Operated Prostate Cancer Patients according to the Total PSA/FT Ratio
Authors: Porcaro Antonio B. , Petrozziello Aldo , Romano Mario , Sava Teodoro , Ghimenton Claudio , Caruso Beatrice , Migliorini Filippo , Zecchini Antoniolli Stefano , Rubilotta Emanuele , Lacola Vincenzo , Monaco Carmelo , Comunale Luigi
Published: December 2010

Objectives: Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. Patients and Methods: The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≧7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≧7) prostate cancer. Results: Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. Conclusions: According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed.
Effect of Antenatal Corticosteroid Treatment on Lung Function in Full-Term Newborn Infants
Authors: Hjalmarson Ola , Sandberg Kenneth L.
Published: December 2010

Background: Antenatal treatment of pregnant women with corticosteroids in order to stimulate surfactant production has been shown to be effective. However, lung structure is also affected by the treatment. Objective: We tested the hypothesis that changes within lung acini, induced by maternal corticosteroid treatment, persist during lung development. Methods: Twenty-two healthy infants, whose mothers were treated with up to three doses of betamethasone at 25–33 weeks of pregnancy because of preterm labour, but where labour terminated and the infants were born at term, were studied at term and compared to a group of 50 healthy newborn infants without prenatal treatment with corticosteroids. Gas-mixing efficiency was measured in terms of moment ratio with a nitrogen washout method together with functional residual capacity. Mechanical parameters were assessed with the single occlusion technique. Results: There were no signs of disturbed gas mixing or changed lung volume or mechanics in the treated group. Conclusion: The result contributes to an emerging body of evidence that antenatal treatment with corticosteroids does not permanently affect lung structure or function.
Role of Short-Term Antibiotic Therapy at the Moment of Catheter Removal after Laparoscopic Radical Prostatectomy
Authors: Pinochet Rodrigo , Nogueira Lucas , Cronin Angel M. , Katz Darren , Rabbani Farhang , Guillonneau Bertrand , Touijer Karim
Published: December 2010

Objective: To assess the role of short-term antibiotic therapy (ABT) in preventing urinary tract infection (UTI) after catheter removal following laparoscopic radical prostatectomy (LRP). Methods: 729 consecutive patients underwent LRP by one of two surgeons. One surgeon systematically prescribed a 3-day course of ABT (ciprofloxacin) starting the day before catheter removal; the other surgeon did not. The groups were compared for the incidence of symptomatic UTI occurring within 6 weeks after catheter removal. Results: ABT was given to 261 of 713 patients (37%), while the remaining 452 patients (63%) did not receive ABT. After catheter removal, UTI was observed less frequently among patients receiving ABT: 3.1 vs. 7.3% in those not receiving ABT (p = 0.019). A number needed to treat to prevent 1 UTI is 24. Hospital readmission for febrile UTI was observed only in patients who did not receive ABT (n = 5, 1.1 vs. 0%, p = 0.16). One would need to prescribe ABT for 91 LRP patients to prevent 1 case of febrile UTI. Conclusions: ABT at the time of catheter removal reduced the risk of postoperative UTI after LRP. One would need to prescribe ABT to 24 patients to prevent 1 case of UTI.
Changes in Diffusion-Weighted Images for Visualizing Prostate Cancer during Antiandrogen Therapy: Preliminary Results
Authors: Nemoto Kaoru , Tateishi Toshiki , Ishidate Takuzo
Published: December 2010

Objectives: To assess the potential of diffusion-weighted imaging (DWI) for monitoring the response to antiandrogen therapy in prostate cancer. Methods: After patients had undergone 6 months of antiandrogen therapy, we investigated the time-course changes in findings obtained from DWI compared to the findings obtained from T2-weighted (T2W) images, transrectal ultrasound (TRUS), and prostate-specific antigen (PSA) kinetics. Results: The time-course changes in T2W images, TRUS, and PSA kinetics following antiandrogen therapy in the present study were consistent with previous reports. In all patients, the posttreatment hypointense signals on DWI were attenuated. Identification of tumor location was difficult on the basis of changes in magnetic resonance imaging findings following antiandrogen therapy due to the remarkable reduction of the total prostatic volume. Three patients exhibited residual tumors that were easily visualized, and apparent diffusion coefficient values increased after treatment in these patients. However, in 1 patient with neuroendocrine differentiation during antiandrogen therapy, DWI findings revealed that the hypointense signal in the prostate became progressively more pronounced. However, this case showed a low PSA recurrence without remarkable changes in the T2W images. Conclusions: The preliminary results suggest that DWI is useful to understand clinical significance of PSA kinetics in patients with low PSA recurrence during antiandrogen therapy.
Y-Chromosome Disomy and Trisomy in Scarabaeid and Cerambycid Beetles
Authors: Dutrillaux A.M. , Dutrillaux B.
Published: December 2010

In a series of about 500 specimens, including 420 males, of karyotyped Polyphaga beetles, 5 males with chromosome Y aneuploidy were detected. One male of each Dicronorrhina derbyana oberthuri (Scarabaeidae), Agapanthia violacea and Morimus funereus (Cerambycidae) were XYY, and 2 probably related and sterile males of Marmylida marginella (Scarabaeidae) were XYYY. These and literature data suggest that Y chromosome aneuploidies are much more frequent in polyphagan beetles than any other group of animals with an XY/XX sex determinism. The origin of this particularity probably lies in the unique mode of sex chromosome association at meiosis I: it is not synaptic but realized through nucleolar proteins forming the well-known parachute-like structure (Xyp). This has 2 possible consequences. The first one is the regular association of several sex chromosomes at metaphase I and segregation at anaphase I. It allows, for instance, XYY (Xyyp) males to procreate XYY sons. The second consequence is the occasional remain of nucleolar proteins embedding sex chromosomes in spermatocytes II. We propose that it could impede the correct segregation of Y chromatids after centromere split at anaphase II, and contribute to form YY gametes by XY males and YYY gametes by XYY males. The tendency for increasing the number of Ys would not be strongly limited at the XY level, but only at the XYY level by male infertility at higher Y ploidies.
Repetitive DNAs and Differentiation of Sex Chromosomes in Neotropical Fishes
Authors: Cioffi M.B. , Camacho J.P.M. , Bertollo L.A.C.
Published: December 2010

The processes working on sex chromosome differentiation are still not completely understood. However, the accumulation of repetitive DNA sequences has been shown to be one of the first steps in the early stages of such differentiation. In addition, regions with suppressed or no recombination have a potential to accumulate these DNA sequences and, for this reason, the absence of recombination between the sex chromosomes favors, by itself, the accumulation of repetitive sequences on these chromosomes during evolution. The diversity of sex-determining mechanisms in fish, alongside with the absence of heteromorphic sex chromosomes in many species, makes this group a useful model to better understand evolutionary processes of sex chromosomes in vertebrates, considering that fish occupy the basal position in the phylogeny of this group. In this review we draw attention to a preferential accumulation and enrichment in repetitive DNAs in sex chromosomes of many neotropical fish species in comparison with autosomes. This phenomenon has been observed between both morphologically differentiated and nascent sex chromosome systems, which highlight the potential role of these sequences in the differentiation of fish sex chromosomes generating differences in morphology and size between them.
C-Banding/DAPI and in situ Hybridization Reflect Karyotype Structure and Sex Chromosome Differentiation in Humulus japonicus Siebold & Zucc.
Authors: Grabowska-Joachimiak A. , Mosiolek M. , Lech A. , Góralski G.
Published: December 2010

Japanese hop (Humulus japonicus Siebold & Zucc.) was karyotyped by chromosome measurements, fluorescence in situ hybridization with rDNA and telomeric probes, and C-banding/DAPI. The karyotype of this species consists of sex chromosomes (XX in female and XY1Y2 in male plants) and 14 autosomes difficult to distinguish by morphology. The chromosome complement also shows a rather monotonous terminal distribution of telomeric repeats, with the exception of a pair of autosomes possessing an additional cluster of telomeric sequences located within the shorter arm. Using C-banding/DAPI staining and 5S and 45S rDNA probes we constructed a fluorescent karyotype that can be used to distinguish all autosome pairs of this species except for the 2 largest autosome pairs, lacking rDNA signals and having similar size and DAPI-banding patterns. Sex chromosomes of H. japonicus display a unique banding pattern and different DAPI fluorescence intensity. The X chromosome possesses only one brightly stained AT-rich terminal segment, the Y1 has 2 such segments, and the Y2 is completely devoid of DAPI signal. After C-banding/DAPI, both Y chromosomes can be easily distinguished from the rest of the chromosome complement by the increased fluorescence of their arms. We discuss the utility of these methods for studying karyotype and sex chromosome evolution in hops.
Contrasting rDNA Evolution in Lima Bean (Phaseolus lunatus L.) and Common Bean (P. vulgaris L., Fabaceae)
Authors: Almeida C. , Pedrosa-Harand A.
Published: December 2010

Phaseolus vulgaris has two 5S rDNA sites in chromosomes 6 and 10 and from two up to nine 45S rDNA sites depending on the accession. The presence of three 45S rDNA sites, in chromosomes 6, 9 and 10, is considered the ancestral state for the species. For P. lunatus, only one 5S and one 45S rDNA sites in distinct chromosomes were known. In order to investigate the homeologies among these rDNA-bearing chromosomes and the stability of the rDNA sites in P. lunatus, rDNA and P. vulgaris chromosome-specific probes were hybridized in situ to P. lunatus. The chromosomes bearing the 5S and the 45S rDNA of P. lunatus are homeologous to chromosomes 10 and 6 of P. vulgaris, respectively. In contrast to the common bean, no variation in the number of rDNA loci was detected, except for a duplication of the 5S rDNA in the same chromosome in a small group of cultivars. These results suggest that the 5S rDNA site in chromosome 10 and the 45S rDNA site in chromosome 6 represent the ancestral loci in the genus. The 5S rDNA site in chromosome 10 of P. vulgaris is located in the long arm, while in P. lunatus it is present in the short arm, suggesting the occurrence of a transposition or a pericentric inversion after separation of both lineages.
The Karyology of Uraeotyphlus gansi, and Its Implications for the Systematics and Evolution of Uraeotyphlidae (Amphibia: Gymnophiona)
Authors: Venu G. , Rajendran A. , Venkatachalaiah G. , Gower D.J.
Published: December 2010

The gross karyotype of the uraeotyphlid caecilian Uraeotyphlus gansi is described as comprising 2n = 42 and fundamental number = 58. These are the first karyotype data for any species of malabaricus-group Uraeotyphlus, and the diploid number is the same as those ichthyophiids thus far studied and differs from the oxyurus-group Uraeotyphlus (2n = 36). These data support the recognition of two species groups within Uraeotyphlus, the monophyly of the oxyurus group, and the understanding that the ancestral diatriatan was more ichthyophiid- than uraeotyphlid-like.
Carotid Atherosclerotic Markers in CADASIL
Authors: Mawet Jérôme , Vahedi Katayoun , Aout Mounir , Vicaut Eric , Duering Marco , Touboul Pierre Jean , Dichgans Martin , Chabriat Hugues
Published: December 2010

Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL. Methods: Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded.Results: Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01). Conclusion: The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results.
Chronic Kidney Disease in Patients with Acute Intracerebral Hemorrhage: Association with Large Hematoma Volume and Poor Outcome
Authors: Molshatzki Noa , Orion David , Tsabari Rakefet , Schwammenthal Yvonne , Merzeliak Oleg , Toashi Maya , Tanne David
Published: December 2010

Background: Chronic kidney disease (CKD) is associated with both a risk of adverse vascular outcome and a risk of bleeding. We have tested the hypothesis that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated with poor outcome and with larger hematoma volume. Methods: We examined the association between CKD and ICH characteristics and outcome within a prospective cohort study of consecutive patients hospitalized with an acute stroke and followed for 1 year. CKD was categorized by the estimated baseline glomerular filtration rate into moderate/severe impairment (<45), mild impairment (45–60) and no impairment (>60 ml/min/1.73 m2). Results: Among 128 patients with an ICH (mean age = 71.7 ± 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7% moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69–10.90) compared to patients with no impairment. The hematoma volumes [median (25–75%)] were 15.3 ml (5.4–37.5) in patients with no impairment, 16.6 (6.8–36.9) in mild impairment and 50.2 (10.4–109.1) in moderate/severe impairment (p = 0.009). The location of the hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39% with moderate/severe impairment (p = 0.02). Patients with moderate/severe impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold higher odds of lobar location (95% CI = 1.59–24.02) as compared to no impairment. Further adjustment for antiplatelet use and for presence of leukoaraiosis attenuated the association with hematoma volume (p = 0.15), while moderate/severe impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18–24.14) for lobar location. Conclusions: Presence of moderate/severe CKD among patients with ICH is associated with larger, lobar hematomas and with poor outcome.
Hyponatremia and Inflammation: The Emerging Role of Interleukin-6 in Osmoregulation
Authors: Swart Reinout M. , Hoorn Ewout J. , Betjes Michiel G. , Zietse Robert
Published: December 2010

Although hyponatremia is a recognized complication of several inflammatory diseases, its pathophysiology in this setting has remained elusive until recently. A growing body of evidence now points to an important role for interleukin-6 in the non-osmotic release of vasopressin. Here, we review this evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6 with vasopressin. The importance of these connections extends to several clinical scenarios of hyponatremia and inflammation, including hospital-acquired hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and hyponatremia in the elderly. Besides insights in pathophysiology, the recognition of the propensity for antidiuresis during inflammation is also important with regard to monitoring patients and selecting the appropriate intravenous fluid regimen, for which recommendations are provided.
Sentinel Lymph Node Biopsy Status Is a Key Parameter to Stratify the Prognostic Heterogeneity of Malignant Melanoma in High-Risk Tumors >4.0 mm
Authors: Göppner Daniela , Ulrich Jens , Pokrywka Anna , Peters Brigitte , Gollnick Harald , Leverkus Martin
Published: December 2010

Background: The value of sentinel lymph node biopsy (SLNB) as a useful strategy to assess the risk of future metastasis in high-risk melanomas (>4.0 mm) is controversially discussed. Objectives: In a single-center retrospective study, the prognostic relevance of SLNB and other risk factors in the subgroup of melanomas >4.0 mm was investigated and compared to previously published results. Methods: Using Kaplan-Meier estimates and Cox regressions, we assessed the prognostic relevance of SLNB in our subcohort of 87 patients with thick melanomas >4.0 mm (T4). The mean follow-up for this subgroup was 51 months. We compared SLN value as compared to ulceration. Results: SLN and ulceration, analyzed as separate risk factors as well as their combination, predicted a highly reduced life expectancy in terms of recurrence-free survival (RFS) in our cohort of patients. SLN, but not ulceration, also predicted overall survival (OS). Conclusions: Positive SLNB is an essential predictor of RFS and OS in T4 melanoma patients, whereas ulceration lacked significance with respect to OS in our cohort. Our data thus suggest the routine use of SLNB also for T4 melanoma and may therefore allow to optimize risk-stratified therapeutic regimens.
Vitamin D, UV, and Skin Cancer in the Elderly: To Expose or Not to Expose?
Authors: Glossmann Hartmut
Published: December 2010

There is mounting concern about vitamin D insufficiency, especially in the ageing population. Increases in indoor lifestyle, obesity, car travel, clothing habits, the use of photo-protective makeup, and campaigns driven by dermatologists, governments, and the cosmetic industry to avoid or protect against the sun as much as possible are contributing to this trend. In a recent article in Gerontology, Barysch et al. [1] recommend that the ageing population avoid any ‘intentional’ UV radiation as well as ‘minimize sun exposure’ based on known dangers of developing skin cancer. They warn that ‘studies with vitamin D supplements reported increased risks of prostate and esophagus cancer as well as atopy in childhood’ and concluded that ‘adequate levels of vitamin D are essential for the elderly’, but do not suggest which level is optimal. I will argue that the ageing population should keep their serum 25-(OH)-vitamin D3 (25-(OH)-D) levels in the 75–100 nmol/l range. An oral cholecalciferol intake of ∼2,000 IU/day is recommended as a supplement throughout the year for those who cannot enjoy the sun in summer or only during ‘vitamin D winter’ for the others.
Medical and Economic Interest of the Use of Cryosurgery in the Instrumental Treatment of Atrial Fibrillation
Authors: Fonteneau Amandine , Petit Abir , Piccardo Alessandro , Marticho Paul , Bernardy Aurore , Lewandowski Elisabeth , Desablens Françoise , Caus Thierry
Published: December 2010

Introduction: In order to definitively integrate cryosurgery for the surgical treatment of atrial fibrillation (AF) into the therapeutic armamentarium, the medical and economic impact of its use on a population of patients with a high risk of recurrence of postoperative AF must be evaluated. Method: An observational study of patients who benefited from cryosurgery between July 2006 and December 2008 was performed. The cost of consumables and hospitalization was determined and compared to that of a control group of 27 patients with preoperative AF that had not benefited from cryosurgery. Results: Twenty-nine patients benefited from cryosurgery during a mitral (65.5%) or aortic intervention (37.9%) to treat a paroxystic (44.8%) or permanent AF (55.2%). More than half of them (58.6%) had a 12-month follow-up; 82.4% of these patients showed a permanent sinus rhythm and 32.6% had stopped their antiarrhythmic medication. There was no significant difference between the duration and cost of hospitalization for the 2 groups. Conclusion: Cryosurgery provides a clear clinical and economic advantage with no recurrence of AF, and it reduces antiarrhythmic medication treatment.
Antisense Inhibition of S6 Kinase 1 Produces Improved Glucose Tolerance and Is Well Tolerated for 4 Weeks of Treatment in Rats
Authors: Younis H.S. , Hirakawa B. , Scott W. , Tran P. , Bhat G. , Affolter T. , Chapman J. , Heyen J. , Chakravarty K. , Alton G.
Published: December 2010

p70 ribosomal S6 kinase 1 (S6K1) is implicated in the pathogenesis of type 2 diabetes as knockout mice are hypoinsulinemic, hypersensitive to insulin treatment and are less susceptible to obesity-induced insulin resistance. Although S6K1 knockout mice provide important information on the biology of this target, the therapeutic relevance of S6K1 inhibition in adult animals is unknown. Thus, this research evaluated the potential safety and efficacy of S6K1 inhibition using antisense oligonucleotides (ASO) in mature Sprague-Dawley rats. Male rats treated with S6K1 ASO (25 or 50 mg/kg, 2×/week × 4 weeks) had a marked reduction (>90%) of S6K1 mRNA in the liver and epididymal fat and no effect on hepatic S6K2 expression. The decrease in S6K1 mRNA translated to decreased (>80%) S6K1 protein and kinase activity in the liver at the 50-mg/kg dose. The animals tolerated the S6K1 treatment well with no signs of clinical toxicity. A reduction in body weight gain was observed within 2 weeks of S6K1 ASO treatment. At 4 weeks, body weight gain was reduced by up to 25% in the 50 mg/kg group with a commensurate decrease (14%) in food consumption. A decrease in heart weight in the 50 mg/kg group was observed and not associated with cardiac injury or dysfunction. In an oral glucose tolerance test, S6K1-ASO-treated animals demonstrated a dose-dependent improvement in systemic glucose utilization and had reduced fasting insulin levels. Hepatic gene microarray analysis identified dose-dependent elevations in igfbp1, acss2 and acat2 gene expression in S6K1-ASO-treated animals. These results suggest that inhibition of S6K1 for up to 4 weeks may be therapeutically relevant to induce insulin sensitization and attenuate weight gain with low risk for serious toxicity.
False Positive Newborn Screening Results Are Not Always Benign
Authors: Morrison D.R. , Clayton E.W.
Published: December 2010

Objective: Our goal was to assess the impact on families of receiving abnormal newborn screening results. Patients and Methods: We conducted telephone interviews with parents of 3 groups of children who had received abnormal newborn screening results: (1) false positive but otherwise healthy (FP, n = 28), (2) true positive (TP, n = 20), and (3) false positive with other medical conditions (FP + other, n = 12). Interviews, based on the instruments developed by Waisbren et al. [J Pediatr Psychol 2004;29:565–570], included open- and close-ended questions as well as the Parental Stress Index (PSI). Results: In response to open ended questions, FP parents expressed concern about having more children and identified numerous problems with how they were told about newborn screening. Parents of FP + other reported the most stress, followed by parents of children with metabolic disease. Nonetheless, almost 10% of FP parents reported clinically significant stress as well as worry about their child’s health and future. Conclusions: False positive newborn screening results cause some parents to experience stress and long-term worry. Although more work is needed to learn how well these sequelae can be averted by more effective communication in the pre- and postnatal periods, these effects need to be considered in deciding whether to add new disorders to newborn screening panels.
Paroxetine Rapidly Modulates the Expression of Brain-Derived Neurotrophic Factor mRNA and Protein in a Human Glioblastoma-Astrocytoma Cell Line
Authors: Angelucci Francesco , Croce Nicoletta , Spalletta Gianfranco , Dinallo Vincenzo , Gravina Paolo , Bossù Paola , Federici Giorgio , Caltagirone Carlo , Bernardini Sergio
Published: December 2010

Neuronal upregulation of the brain-derived neurotrophic factor (BDNF) gene appears to be a crucial factor for the efficacy of antidepressants. However, besides neurons, little information is present on the modulation of BDNF by antidepressants at RNA and protein levels in other cell types of the central nervous system. Glial cells are able to store and release BDNF, and it has been hypothesized that glial dysfunction may contribute to the etiopathogenesis of depression. Thus, in this study we used the human glioblastoma-astrocytoma cell line U87 exposed to the antidepressant drug paroxetine, and evaluated BDNF mRNA and protein expression. In addition, since the BDNF gene can be posttranscriptionally modulated by a family of microRNA, we also evaluated the levels for one of these microRNA (miR-30a-5p) in the U87 cell line during paroxetine treatment. We found that paroxetine treatment rapidly increased BDNF in U87 cells, resulting from an induction of BDNF mRNA expression and de novo protein synthesis, and that these increases occurred in a time-dependent manner. Paroxetine effects were evident at 6 h of incubation for BDNF mRNA and at 12 h for BDNF protein. In addition, the transcriptional BDNF inhibitor miR-30a-5p was also overexpressed at 6 and 12 h of paroxetine incubation. These findings indicate that the U87 cell line, an in vitro model of glial cells, rapidly responds to paroxetine by increasing BDNF production, and that these effects are potentially limited by microRNA induction. These data may contribute to explain the action of paroxetine on cells of nonneuronal origin.
Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients
Authors: Fellgiebel Andreas , Keller Isabel , Martus Peter , Ropele Stefan , Yakushev Igor , Böttcher Tobias , Fazekas Franz , Rolfs Arndt
Published: December 2010

Background: Fabry disease (FD) is a rare hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age. Enlarged basilar artery diameters (BADs) have been demonstrated in FD, and we hypothesize that they might be useful for the screening of FD in young stroke patients. The aim of this study was to compare BADs of young stroke patients without FD to those of FD patients and of healthy age-matched controls. Methods: BADs were measured using MR angiography in 3 age- and gender-matched groups: 25 FD patients (aged 36.5 ± 11.0 years), 26 non-FD stroke patients and 20 healthy controls. Results: Compared to the non-FD stroke patients, FD patients had significantly enlarged BADs. FD patients could be significantly separated from stroke patients by BADs (area under the curve = 0.89, 95% confidence interval 0.81–0.98). Eighty-six percent of all subjects could be correctly classified by BADs (sensitivity 84%, specificity 88.5%). Conclusions: Enlarged BADs were able to detect FD within a cohort of FD, stroke patients and healthy controls. BAD measurement could be an easily obtainable and sensitive screening tool for FD in young stroke patients.
Podocyte Number in the Maturing Rat Kidney
Authors: Bai Xiao Yan , Basgen John M.
Published: December 2010

Background/Aims: The podocyte is an important cell for maintaining the normal structure and function of the glomerulus. In recent years much attention has been given to the number of podocytes in glomeruli. During this time there has been a debate as to whether podocytes can divide after the capillary-loop stage of development. The aim of this study was to use an unbiased counting method to determine if podocyte number increases after the capillary-loop stage of development. Methods:The fractionator/disector method was used to count podocytes in glomeruli from rats aged 1 day, 5, 12, and 24 weeks. Glomerular volume was also measured with the unbiased Cavalieri principle and used to calculate the density of podocytes per glomerulus. Results: The number of podocytes did not increase from the capillary-loop stage of glomerular development to 24 weeks of age. Glomerular volume increased 3.6-fold during this time, which resulted in a decrease of podocyte density as the rats aged. Conclusion:The study documents that the number of podocytes is stable after the capillary-loop stage of glomerular development. The data does not confirm but adds evidence that podocytes do not divide from the capillary-loop stage of glomerular development to 24 weeks of age in the normal rat.
The Danish Alzheimer Intervention Study: Rationale, Study Design and Baseline Characteristics of the Cohort
Authors: Waldemar G. , Waldorff F.B. , Buss D.V. , Eckermann A. , Keiding N. , Rishøj S. , Siersma V. , Sørensen J. , Sørensen L.V. , Vogel A.
Published: December 2010

Background: There is a lack of appropriately designed trials investigating the efficacy of psychosocial interventions for patients with mild dementia and their family caregivers. This paper reports the rationale and design of the Danish Alzheimer Disease Intervention Study and baseline characteristics of the cohort. Methods: The study was a 1-year multicentre randomized controlled rater-blinded trial with randomization to follow-up and a multifaceted semitailored intervention programme or to follow-up only (with extension of follow-up to 3 years). The intervention included a counselling programme, teaching courses, written information and logbooks. The outcomes included clinical efficacy parameters, patient satisfaction and health economic consequences. Results: A total of 330 patients and their 330 caregivers were included during a period of 18 months. The majority (65.2 %) of the caregivers were spouses. At inclusion the mean age of the patients and caregivers was 76.2 and 66.0 years, respectively. Conclusion: The study will explore the added value of a multifaceted intervention programme and contribute to the design of future interventions for patients with mild dementia and their caregivers.
Patterns of Mind-Body Therapies in Adults with Common Neurological Conditions
Authors: Erwin Wells Rebecca , Phillips Russell S. , McCarthy Ellen P.
Published: December 2010

Background: Over 40% of adults with common neurological conditions use complementary and alternative medicine, and mind-body therapies are the most commonly used form. Our objective was to describe mind-body use in adults with common neurological conditions. Methods: We compared mind-body use between adults with and without common neurological conditions (regular headaches, migraines, back pain with sciatica, strokes, dementia, seizures or memory loss) using the 2007 National Health Interview Survey of 23,393 sampled American adults. Results: Adults with common neurological conditions used mind-body therapies more frequently than those without (24.5 vs. 16.6%, p < 0.0001); differences persisted after adjustment. Deep breathing exercises, meditation and yoga were used most frequently. Nearly 70% of the adults with common neurological conditions did not discuss their mind-body use with their health care provider. Those with neurological conditions used mind-body therapies more than those without these conditions because of provider recommendation (26 vs. 13%) or because conventional treatments were perceived ineffective (12 vs. 4%) or too costly (7 vs. 2%), respectively. Conclusions: Mind-body therapies are used more frequently among adults with common neurological conditions, more often when conventional treatments were perceived ineffective. More research is warranted on the efficacy of mind-body use for common neurological conditions.
Docosahexaenoic Acid Is an Independent Predictor of All-Cause Mortality in Hemodialysis Patients
Authors: Hamazaki Kei , Terashima Yoshihiro , Itomura Miho , Sawazaki Shigeki , Inagaki Hitoshi , Kuroda Masahiro , Tomita Shin , Hirata Hitoshi , Inadera Hidekuni , Hamazaki Tomohito
Published: December 2010

Background: Dietary n–3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid have been shown to reduce cardiovascular mortality. Patients on hemodialysis (HD) have a very high mortality from cardiovascular disease. Fish consumption reduces all-cause mortality in patients on HD. Moreover, n–3 PUFAs, especially DHA levels in red blood cells (RBCs), are associated with arteriosclerosis in patients on HD. The aim of this study was to determine whether DHA levels in RBCs predict the mortality of patients on HD in a prospective cohort study. Methods: A cohort of 176 patients (64.1 ± 12.0 (mean ± SD) years of age, 96 men and 80 women) under HD treatment was studied. The fatty acid composition of their RBCs was analyzed by gas chromatography. Results: During the study period of 5 years, 54 deaths occurred. After adjustment for 10 confounding factors, the Cox hazard ratio of all-cause mortality of the patients on HD in the highest DHA tertile (>8.1%, 15 deaths) was 0.43 (95% CI 0.21–0.88) compared with those patients in the lowest DHA tertile (<7.2%, 21 deaths). Conclusion: The findings suggest that the level of DHA in RBCs could be an independent predictor of all-cause mortality in patients on HD.