bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Combined Oral Therapy with Tadalafil and Alfuzosin: An Integrated Approach to the Management of Patients with Lower Urinary Tract Symptoms and Erectile Dysfunction. Preliminary Report
Authors: Liguori Giovanni , Trombetta Carlo , De Giorgi Gioacchino , Pomara Giorgio , Maio Giuseppe , Vecchio Daniele , Ocello Giuseppe , Ollandini Giangiacomo , Bucci Stefano , Belgrano Emanuele 
Published: December 2008

ABSTRACT

Introduction
Alpha1-blockers (AB) are the first-line monotherapy for lower urinary tract symptoms (LUTS). Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction (ED). Numerous studies have supposed a significant association between ED and LUTS, but a causal relationship cannot be established.

Aim
The aim was to evaluate the efficacy of a combined therapy with an AB (alfuzosin) and PDE5 inhibitors (tadalafil) in patients with LUTS and ED.

Methods
This was a randomized, open-label, three-arm study. A total of 66 men complaining of ED and LUTS were included in the study. Patients were assessed at baseline and after 12 weeks of study treatment, and then underwent randomized allocation to either alfuzosin 10 mg once a day (22 patients) or tadalafil 20 mg on alternative days (21 patients), or a combination of both (23 patients).

Main Outcome Measures
All participants completed the erectile function domain of the International Index of Erectile Function (IIEF-EF) and the International Prostatic Symptom Score (IPSS). Other efficacy variables included maximum urinary flow rate (Qmax) and medium urinary flow rate (Qave).

Results
IIEF-EF tended to improve with alfuzosin alone (+15%), while it was clearly improved with tadalafil alone (+36.3%). The greatest improvement was experienced with the combination therapy (+37.6%). Improvement in Qmax was observed in all groups, but patients receiving combination therapy had greater improvement (29.6%) than patients receiving either only alfuzosin (21.7%) or only tadalafil (9.5%). IPSS was significantly improved in alfuzosin group (27.2%), was more marked with the combination therapy (41.6%), and a small increase, although not significant, was also observed with tadalafil (8.4%).

Conclusions
Combined therapy improved ED and LUTS as demonstrated by the significant improvement in uroflowmetry measures and in IPSS and IIEF-EF scores. A significant improvement was also observed in quality of life assessments. The beneficial effects of tadalafil on LUTS similar to the benefits of alfuzosin on ED, although present, were smaller.
Persistent Genital Arousal Disorder in 18 Dutch Women: Part II—A Syndrome Clustered with Restless Legs and Overactive Bladder
Authors: Waldinger Marcel D. , Schweitzer Dave H. 
Published: December 2008

ABSTRACT

Introduction
A systematic study in women with persistent genital arousal disorder (PGAD) is urgently needed to develop its clinical management.

Aim
To investigate the features, possible causes, and treatment of PGAD.

Methods
Eighteen women who fulfilled the five criteria for PGAD were included in the study. In-depth interviews were combined with laboratory and imaging studies as reported in Part I of the study. Clinical responses were observed with drugs exerting activity against a number of different neuro-regulatory mechanisms.

Main Outcome Measures
Detailed descriptions and clustering of some well established clinical syndromes.

Results
The majority of women experienced PGAD during early menopause without pre-existing psychiatric disorders and laboratory abnormalities. Most women had difficulties in describing the quality of the genital sensations. These were described in various terms and were diagnosed as dysesthesias and paresthesias. Their intensity was most severe during sitting. A few women reported PGAD during pregnancy and premenstrual. The majority of women also reported preexistent or coexistent restless legs syndrome (RLS) and overactive bladder syndrome (OBS). These strongly associated morbidities point into the direction of a clinical cluster, which harbors PGAD or PGAD plus these typical other disorders. Notably, as in RLS and OBS, it appeared that daily treatment with clonazepam 0.5–1.5 mg was effective in 56% of PGAD women. Also, oxazepam 10 mg and tramadol 50 mg elicited PGAD-reducing effect.

Conclusions
PGAD seems to belong to a highly associated disease cluster including morbidities, which share an imperative urge to suppress dysesthesias and paresthesias by firm manipulative actions. PGAD—or as proposed by our group, restless genital syndrome (RGS) in the context of its strong association with restless legs—is probably the expression of a nonsexually driven hyperexcitability of the genitals and subsequent attempts to overcome it by genital manipulations.
UV‐B‐induced Oxidative Damage and Protective Role of Exopolysaccharides in Desert Cyanobacterium Microcoleus vaginatus
Authors: Chen Lan‐Zhou , Wang Gao‐Hong , Hong Song , Liu An , Li Cheng , Liu Yong‐Ding 
Published: December 2008

Abstract UV‐B‐induced oxidative damage and the protective effect of exopolysaccharides (EPS) in Microcoleus vaginatus, a cyanobacterium isolated from desert crust, were investigated. After being irradiated with UV‐B radiation, photosynthetic activity (Fv/Fm), cellular total carbohydrates, EPS and sucrose production of irradiated cells decreased, while reducing sugars, reactive oxygen species (ROS) generation, malondialdehyde (MDA) production and DNA strand breaks increased significantly. However, when pretreated with 100 mg/L exogenous EPS, EPS production in the culture medium of UV‐B stressed cells decreased significantly; Fv/Fm, cellular total carbohydrates, reducing sugars and sucrose synthase (SS) activity of irradiated cells increased significantly, while ROS generation, MDA production and DNA strand breaks of irradiated cells decreased significantly. The results suggested that EPS exhibited a significant protective effect on DNA strand breaks and lipid peroxidation by effectively eliminating ROS induced by UV‐B radiation in M. vaginatus.
Immunomagnetic detection of micrometastatic cells in bone marrow in uveal melanoma patients
Authors: Eide Nils , Faye Ragnar S. , Høifødt Hanne K. , Øvergaard Ralf , Jebsen Peter , Kvalheim Gunnar , Fodstad Øystein 
Published: December 2008

Abstract.Purpose:  Our objective was to introduce immunomagnetic separation (IMS) in ocular research by evaluating the possibility of detecting tumour cells in bone marrow (BM) and peripheral blood (PB) samples and validating the captured cells as melanocytic cells.Methods:  Mononuclear cell (MNC) fractions isolated from BM and PB in uveal melanoma patients were examined for tumour cells using our IMS method. Sheep‐anti‐mouse IgG antibody‐coated super paramagnetic particles were conjugated to an anti‐melanoma antibody. Microscopy of the magnetic fraction isolated from MNCs was performed to identify and count the number of bead‐rosetted cells. The finding of at least two rosettes with coated beads in a 20‐μl fraction of a sample was registered as a positive test. The melanocytic nature of the tumour cells was ascertained with a double labelling procedure using fluorescent microparticles.Results:  Using IMS in a study of 328 patients, tumour cells were at initial diagnosis found in BM and PB in 29.9% and 1.6% of cases, respectively. In positive samples, a median of 56 tumour cells (range 2–500) were identified. The captured cells were documented to be of melanocytic origin by the simultaneous binding of fluorescent beads coated with another melanoma‐associated antibody.Conclusions:  The IMS method was sensitive and efficient in the detection of occult melanoma tumour cells in BM. The validity of the immunomagnetic technique was strengthened by verifying the melanocytic characteristics of the isolated cells. The IMS procedure identifies intact, vital tumour cells, permitting further molecular characterization, an advantage which makes this method attractive for extended use. The clinical relevance of the findings will be further investigated in follow‐up studies with repeated sampling and characterization of the isolated tumour cells.
Design and Validation of a Microarray for Detection, Hemagglutinin Subtyping, and Pathotyping of Avian Influenza Viruses
Authors: Gall Astrid , Hoffmann Bernd , Harder Timm , Grund Christian , Höper Dirk , Beer Martin 
Published: December 2008

ABSTRACT

Continuing threats of devastating outbreaks in poultry and of human infections caused by highly pathogenic avian influenza virus (HPAIV) H5N1 emphasize the need for the further development of rapid and reliable methods of virus detection and characterization. Here we report on the design and comprehensive validation of a low-density microarray as a diagnostic tool for the detection and typing of avian influenza virus (AIV). The array consists of one probe for the conserved matrix gene and 97 probes targeting the HA
0
cleavage-site region. Following fragment amplification by a generic PCR approach, the array enables AIV detection, hemagglutinin (HA) subtyping, and pathotyping within a single assay. For validation, a panel of 92 influenza A viruses which included 43 reference strains representing all 16 HA subtypes was used. All reference strains were correctly typed with respect to their HA subtypes and pathotypes, including HPAIV H5N1/Asia, which caused outbreaks in Germany in 2006 and 2007. In addition, differentiation of strains of the Eurasian and North American lineages of the H5 and H7 subtypes was possible. The sensitivity of the microarray for the matrix gene is comparable to that of real-time reverse transcription-PCR (RT-PCR). It is, however, 10- to 100-fold lower than that of real-time RT-PCR with respect to HA subtyping and pathotyping. The specificity of the array was excellent, as no pathogens relevant for differential diagnosis yielded a positive reaction. Validation with field samples included 19 cloacal swab specimens from wild and domestic birds. Influenza A virus was verified in all samples, whereas the HA subtypes could be determined for 14 samples. The results demonstrate that the microarray assay described complements current methods and can accelerate the diagnosis and characterization of AIV.
Longer Intestinal Persistence of
Enterococcus faecalis
Compared to
Enterococcus faecium
Clones in Intensive-Care-Unit Patients
Authors: Ruiz-Garbajosa Patricia , del Campo Rosa , Coque Teresa M. , Asensio Angel , Bonten Marc , Willems Rob , Baquero Fernando , Cantón Rafael 
Published: December 2008

ABSTRACT

The dynamics of intestinal colonization with enterococcal clones in intensive-care-unit (ICU) patients was evaluated. Eight patients admitted directly to the neurosurgical ICU at the Ramón y Cajal University Hospital (Madrid, Spain) from the community and with no overlapping stay during a 10-month period in 2006 were studied. Rectal swab specimens were collected on admission and daily until the patients were discharged. Clonality was determined by pulsed-field gel electrophoresis and multilocus sequence typing. Clonal colonization dynamics were estimated by using two new parameters: the clonal diversity per patient per day (CDPD) and the clonal persistence ratio (CPR).
Enterococcus faecalis
isolates (
n
= 123) and
Enterococcus faecium
isolates (
n
= 66) were resolved into 13 and 15 clones, respectively. The CDPD of
E. faecalis
steadily increased during admission, and
E. faecalis
showed a higher (
P
= 0.001) CPR value than
E. faecium
(0.86 and 0.42, respectively).
E. faecium
, with the exception of an ampicillin-resistant clone belonging to clonal complex 17, frequently appeared as a short-term colonizer, even though the
E. faecalis
clones had significantly (
P
= 0.03) more days under antibiotic exposure than
E. faecium
(77.5 and 65 days/100 colonization days, respectively).
E. faecalis
had a longer persistence than
E. faecium
, except for the CC17 ampicillin-resistant clone, and
E. faecalis
showed a cumulative increase in CDPD, whereas
E. faecium
did not. CDPD and CPR were useful for measuring the dynamics of intestinal colonization with enterococcal clones.
Detection and Isolation of
Campylobacter
Species Other than
C. jejuni
from Children with Crohn's Disease
Authors: Zhang Li , Man Si Ming , Day Andrew S. , Leach Steven T. , Lemberg Daniel A. , Dutt Shoma , Stormon Michael , Otley Anthony , O'Loughlin Edward V. , Magoffin Annabel , Ng Patrick H. Y. , Mitchell Hazel 
Published: December 2008

ABSTRACT

The presence of
Campylobacter
species other than
Campylobacter jejuni
and antibodies to
Campylobacter concisus
in children were investigated. A significantly greater presence of
C. concisus
and higher levels of antibodies to
C. concisus
were detected in children with Crohn's disease (CD) than in controls.
Campylobacter
species other than
C. jejuni
were isolated from intestinal biopsy specimens of children with CD.
Clinic-Based Evaluation of a Rapid Point-of-Care Test for Detection of
Chlamydia trachomatis
in Specimens from Sex Workers in Escuintla, Guatemala
Authors: Sabidó M. , Hernández G. , González V. , Vallès X. , Montoliu A. , Figuerola J. , Isern V. , Viñado B. , Figueroa L. , Casabona J. 
Published: December 2008

ABSTRACT

We evaluated a rapid point-of-care test for the detection of
Chlamydia trachomatis
in specimens from 278 sex workers attending sexually transmitted infection clinics in Guatemala. The sensitivity and the specificity of the test compared to the results of PCR were 62.96% and 99.60%, respectively. The test performed moderately well as a screening tool in a context in which clinical follow-up visits are infrequent.
Identification of Sendai Virus L Protein Amino Acid Residues Affecting Viral mRNA Cap Methylation
Authors: Murphy Andrea M. , Grdzelishvili Valery Z. 
Published: December 2008

ABSTRACT

Viruses of the order
Mononegavirales
all encode a large (L) polymerase protein responsible for the replication and transcription of the viral genome as well as all posttranscriptional modifications of viral mRNAs. The L protein is conserved among all members of the
Mononegavirales
and has six conserved regions (“domains”). Using vesicular stomatitis virus (VSV) (family
Rhabdoviridae
) experimental system, we and others recently identified several conserved amino acid residues within L protein domain VI which are required for viral mRNA cap methylation. To verify that these critical amino acid residues have a similar function in other members of the
Mononegavirales
, we examined the Sendai virus (SeV) (family
Paramyxoviridae
) L protein by targeting homologous amino acid residues important for cap methylation in VSV which are highly conserved among all members of the
Mononegavirales
and are believed to constitute the L protein catalytic and
S
-adenosylmethionine-binding sites. In addition, an SeV L protein mutant with a deletion of the entire domain VI was generated. First, L mutants were tested for their abilities to synthesize viral mRNAs. While the domain VI deletion completely inactivated L, most of the amino acid substitutions had minor effects on mRNA synthesis. Using a reverse genetics approach, these mutations were introduced into the SeV genome, and recombinant infectious SeV mutants with single alanine substitutions at L positions 1782, 1804, 1805, and 1806 or a double substitution at positions 1804 and 1806 were generated. The mutant SeV virions were purified, detergent activated, and analyzed for their abilities to synthesize viral mRNAs methylated at their cap structures. In addition, further studies were done to examine these SeV mutants for a possible host range phenotype, which was previously shown for VSV cap methylation-defective mutants. In agreement with a predicted role of the SeV L protein invariant lysine 1782 as a catalytic residue, the recombinant virus with a single K1782A substitution was completely defective in cap methylation and showed a host range phenotype. In addition, the E1805A mutation within the putative
S
-adenosylmethionine-binding site of L resulted in a 60% reduction in cap methylation. In contrast to the homologous VSV mutants, other recombinant SeV mutants with amino acid substitutions at this site were neither defective in cap methylation nor host range restricted. The results of this initial study using an SeV experimental system demonstrate similarities as well as differences between the L protein cap methylation domains in different members of the
Mononegavirales
.
Nuclear Magnetic Resonance Structure Shows that the Severe Acute Respiratory Syndrome Coronavirus-Unique Domain Contains a Macrodomain Fold
Authors: Chatterjee Amarnath , Johnson Margaret A. , Serrano Pedro , Pedrini Bill , Joseph Jeremiah S. , Neuman Benjamin W. , Saikatendu Kumar , Buchmeier Michael J. , Kuhn Peter , Wüthrich Kurt 
Published: December 2008

ABSTRACT
The nuclear magnetic resonance (NMR) structure of a central segment of the previously annotated severe acute respiratory syndrome (SARS)-unique domain (SUD-M, for “middle of the SARS-unique domain”) in SARS coronavirus (SARS-CoV) nonstructural protein 3 (nsp3) has been determined. SUD-M(513-651) exhibits a macrodomain fold containing the nsp3 residues 528 to 648, and there is a flexibly extended N-terminal tail with the residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. As a follow-up to this initial result, we also solved the structure of a construct representing only the globular domain of residues 527 to 651 [SUD-M(527-651)]. NMR chemical shift perturbation experiments showed that SUD-M(527-651) binds single-stranded poly(A) and identified the contact area with this RNA on the protein surface, and electrophoretic mobility shift assays then confirmed that SUD-M has higher affinity for purine bases than for pyrimidine bases. In a further search for clues to the function, we found that SUD-M(527-651) has the closest three-dimensional structure homology with another domain of nsp3, the ADP-ribose-1"-phosphatase nsp3b, although the two proteins share only 5% sequence identity in the homologous sequence regions. SUD-M(527-651) also shows three-dimensional structure homology with several helicases and nucleoside triphosphate-binding proteins, but it does not contain the motifs of catalytic residues found in these structural homologues. The combined results from NMR screening of potential substrates and the structure-based homology studies now form a basis for more focused investigations on the role of the SARS-unique domain in viral infection.
PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs
Authors: Manzoor Rashid , Sakoda Yoshihiro , Nomura Naoki , Tsuda Yoshimi , Ozaki Hiroichi , Okamatsu Masatoshi , Kida Hiroshi 
Published: December 2008

ABSTRACTIt has been shown that not all but most of the avian influenza viruses replicate in the upper respiratory tract of pigs (H. Kida et al., J. Gen. Virol. 75:2183-2188, 1994). It was shown that A/chicken/Yamaguchi/7/2004 (H5N1) [Ck/Yamaguchi/04 (H5N1)] did not replicate in pigs (N. Isoda et al., Arch. Virol. 151:1267-1279, 2006). In the present study, the genetic basis for this host range restriction was determined using reassortant viruses generated between Ck/Yamaguchi/04 (H5N1) and A/swine/Hokkaido/2/1981 (H1N1) [Sw/Hokkaido/81 (H1N1)]. Two in vivo-generated single-gene reassortant virus clones of the H5N1 subtype (virus clones 1 and 2), whose PB2 gene was of Sw/Hokkaido/81 (H1N1) origin and whose remaining seven genes were of Ck/Yamaguchi/04 (H5N1) origin, were recovered from the experimentally infected pigs. The replicative potential of virus clones 1 and 2 was further confirmed by using reassortant virus (rg-Ck-Sw/PB2) generated by reverse genetics. Interestingly, the PB2 gene of Ck/Yamaguchi/04 (H5N1) did not restrict the replication of Sw/Hokkaido/81 (H1N1), as determined by using reassortant virus rg-Sw-Ck/PB2. The rg-Sw-Ck/PB2 virus replicated to moderate levels and for a shorter duration than parental Sw/Hokkaido/81 (H1N1). Sequencing of two isolates recovered from the pigs inoculated with rg-Sw-Ck/PB2 revealed either the D256G or the E627K amino acid substitution in the PB2 proteins of the isolates. The D256G and E627K mutations enhanced viral polymerase activity in the mammalian cells, correlating with replication of virus in pigs. These results indicate that the PB2 protein restricts the growth of Ck/Yamaguchi/04 (H5N1) in pigs.
Reduced thrombin generation increases host susceptibility to group A streptococcal infection
Authors: Sun Hongmin , Wang Xixi , Degen Jay L. , Ginsburg David 
Published: December 2008

AbstractBacterial plasminogen activators are commonplace among microbial pathogens, implying a central role of host plasmin in supporting bacterial virulence. Group A streptococci (GAS) secrete streptokinase, a specific activator of human plasminogen (PLG). The critical contribution of the streptokinase-PLG interaction to GAS pathogenicity was recently demonstrated using mice expressing human PLG. To examine the importance of thrombin generation in antimicrobial host defense, we challenged mice with deficiency of factor V (FV) in either the plasma or platelet compartment. Reduction of FV in either pool resulted in markedly increased mortality after GAS infection, with comparison to heterozygous F5-deficient mice suggesting a previously unappreciated role for the platelet FV pool in host defense. Mice with complete deficiency of fibrinogen also demonstrated markedly increased mortality to GAS infection relative to controls. Although FV Leiden may be protective in the setting of severe sepsis in humans, no significant survival advantage was observed in GAS-infected mice carrying the FV Leiden mutation. Taken together, our data support the hypothesis that local thrombosis/fibrin deposition limits the survival and dissemination of at least a subset of microbial pathogens and suggest that common variation in hemostatic factors among humans could affect host susceptibility to a variety of infectious diseases.