bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrase interactor 1 (Ini1/hSNF5) is a repressor of basal human immunodeficiency virus type 1 promoter activity
Authors: Boese Annette , Sommer Peter , Holzer Daniela , Maier Reinhard , Nehrbass Ulf
Published: September 2009

Integrase interactor 1 (Ini1/hSNF5/BAF47/SMARCB1), the core subunit of the ATP-dependent chromatin-remodelling complex SWI/SNF, is a cellular interaction partner of the human immunodeficiency virus type 1 (HIV-1) integrase. Ini1/hSNF5 is recruited to HIV-1 pre-integration complexes before nuclear migration, suggesting a function in the integration process itself or a contribution to the preferential selection of transcriptionally active genes as integration sites of HIV-1. More recent evidence indicates, however, that, whilst Ini1/hSNF5 is dispensable for HIV-1 transduction per se, it may have an inhibitory effect on the early steps of HIV-1 replication but facilitates proviral transcription by enhancing Tat function. These partially contradictory observations prompted an investigation of the immediate and long-term effects of Ini1/hSNF5 depletion on the basal transcriptional potential of the virus promoter. Using small interfering RNAs, it was shown that Ini1/hSNF5-containing SWI/SNF complexes mediate transcriptional repression of the basal activity of the integrated HIV-1 long terminal repeat. Transient depletion of Ini1/hSNF5 during integration was accompanied by an early boost of HIV-1 replication. After the reappearance of Ini1/hSNF5, expression levels decreased and this was associated with increased levels of histone methylation at the virus promoter in the long term, indicative of epigenetic gene silencing. These results demonstrate the opposing effects of Ini1/hSNF5-containing SWI/SNF complexes on basal and Tat-dependent transcriptional activity of the HIV-1 promoter. It is proposed that Ini1/hSNF5 may be recruited to the HIV-1 pre-integration complex to initiate, immediately after integration, one of two mutually exclusive transcription programmes, namely post-integration latency or high-level, Tat-dependent gene expression.
Matrilinear phylogeography and demographical patterns of Rutilus rutilus: implications for taxonomy and conservation
Authors: Larmuseau M. H. D. , Freyhof J. , Volckaert F. A. M. , Van Houdt J. K. J.
Published: September 2009

A phylogeographic analysis of mitochondrial DNA sequence variation was carried out to infer the geographical distribution of the genealogical lineages and the historical demography of roach Rutilus rutilus (L.). A total of 265 individuals from 52 sites covering most of the Eurasian distribution range were sequenced for a 475 bp fragment of the mitochondrial cytochrome b gene. The monophyletic roach contained two deep clades that dated back to the Pliocene. The Ponto‐Caspian clade comprised populations from Greece to Siberia with a likely palaeorefugium at the west coast of the Caspian Sea. This clade largely corresponds to individuals with morphological features described as Rutilus heckelii. The west European clade included individuals from central and western Europe with the Danube and Dniester basins as possible palaeorefugia. This clade largely corresponds to individuals with morphological features described as R. rutilus. A suture‐zone of the two main lineages was observed along the coastal region of the Black Sea. The neutrality tests and the mismatch distributions indicated a demographic expansion during the Middle‐Pleistocene for both clades.
Phylogeography of the flathead mullet Mugil cephalus in the north‐west Pacific as inferred from the mtDNA control region
Authors: Jamandre B. W. , Durand J.‐D. , Tzeng W. N.
Published: September 2009

The population genetic structure and historical demography of the flathead mullet Mugil cephalus were investigated using the mtDNA control region (CR) sequences (909–1015 bp) of 126 individuals collected from seven locations in the north‐west Pacific between 2005 and 2007. Haplotype diversity (h = 0·9333–1·000) and nucleotide diversity (π = 0·0046–0·1467) varied greatly among the sampling locations. Phylogenetic analysis of the CR sequences indicated that M. cephalus in the north‐west Pacific belongs to two highly divergent lineages (lineages 1 and 2), with the inferred population structure being closely associated with the distribution of both lineages. Two populations were identified, one from the East China Sea and the other from the South China Sea. The former samples were obtained from Taiwan and Qingdao of north China and associated with lineage 1 haplotypes. The latter samples were collected from the Philippines, Pearl River of South China and two samples from Japan, all of which were associated with lineage 2. Japanese samples from Okinawa and Yokosuka had different degrees of mixing between lineages 1 and 2. Historical demographic variables in both populations indicated that Pleistocene glaciations had a strong impact on M. cephalus in the north‐west Pacific, resulting in a recent demographic decline of the East China Sea population but in demographic equilibrium for the South China Sea population. Japan appears to be a contact zone between lineages 1 and 2, but it may also be indicative of coexistence between resident and migratory populations. Further global studies are required to clarify the taxonomic status of this cosmopolitan species.
Chromosomal location and distribution of As51 satellite DNA in five species of the genus Astyanax (Teleostei, Characidae, Incertae sedis)
Authors: Kantek D. L. Z. , Vicari M. R. , Peres W. A. M. , Cestari M. M. , Artoni R. F. , Bertollo L. A. C. , Moreira‐Filho O.
Published: September 2009

Constitutive heterochromatin makes up a substantial portion of the genome of eukaryotes and is composed mainly of satellite DNA repeating sequences in tandem. Some satellite DNAs may have been derived from transposable elements. These repetitive sequences represent a highly dynamic component of rapid evolution in genomes. Among the genus Astyanax, the As51 satellite DNA is found in species that have large distal heterochromatic blocks, which may be considered as derived from a transposable DNA element. In the present study, As51 satellite DNA was mapped through in situ fluorescent hybridization in the chromosomes of five species of the genus. The possible roles of this type of saltatory DNA type in the genome of the species are discussed, along with its use for the phylogenetic grouping of the genus Astyanax, together with other shared chromosomal characters. However, the number of As51 clusters is presented as a homoplastic characteristic, thereby indicating evident genomic diversification of species with this type of DNA.
Knock down of the dual functional protein apurinic /apyrimidinic endonuclease 1 enhances the killing effect of hematoporphrphyrin derivative‐mediated photodynamic therapy on non‐small cell lung cancer cells in vitro and in a xenograft model
Authors: Yang Zhen‐Zhou , Li Meng‐Xia , Zhang Yun‐Song , Xiang De‐Bing , Dai Nan , Zeng Lin‐Li , Li Zeng‐Peng , Wang Ge , Wang Dong
Published: September 2009

Photodynamic therapy (PDT) is considered to be effective treatment for many cancers including lung cancer, head and neck cancers, and prostate cancer. It uses the combination of nontoxic photosensitizers and harmless visible light to generate reactive oxygen species and kill cells. However, DNA repair and reactive oxygen species‐induced signaling pathway activation play crucial roles in cellular response to PDT and may also result in therapeutic limitation of PDT. To improve the cancer therapeutic efficacy of PDT, we targeted apurinic/apyrimidinic endonuclease (APE1), which is essential for both DNA repair and redox regulation of gene transcription, as a potential candidate for PDT combined gene therapy. In our study, an adenovirus‐mediated APE1 silencing strategy was introduced to test its therapeutic enhancement for the non‐small cell lung cancer cell line A549 both in vitro and in vivo after hematoporphrphyrin derivative (HpD)‐mediated PDT. The adenovirus vector Ad5/F35‐shAPE1 was validated to significantly suppress the protein expression of APE1 in cultured A549 cell and in its xenograft of nude mice. Ad5/F35‐shAPE1 effectively inhibited APE1 protein upregulation induced by PDT and resulted in an increase in A549 cell killing by photoirradiation compared with the hematoporphrphyrin derivative‐PDT alone group. Ad5/F35‐shAPE1 suppressed the DNA repair capacity for single‐strand breaks and abolished the activation of some stress‐related transcription factors such as hypoxia‐induced factor (HIF)‐1 that consequently lead to increased cell apoptosis after PDT. Additionally, knock down of APE1 enhanced the tumor suppression efficacy of PDT on the A549 xenograft. Our study indicated that APE1‐targeted gene therapy combined with PDT is a promising strategy for enhancement of the efficacy of PDT in treatment of non‐small cell lung cancer. (Cancer Sci 2009)
Clinical value of minor responses after 4 doses of rituximab in Waldenström macroglobulinaemia: a follow‐up of the Eastern Cooperative Oncology Group E3A98 trial
Authors: Gertz Morie A. , Abonour Rafat , Heffner Leonard T. , Greipp Philip R. , Uno Hajime , Rajkumar S. V.
Published: September 2009

Waldenström macroglobulinaemia is a low‐grade, lymphoplasmacytic lymphoma that is responsive to rituximab. We report the role of a minor response in predicting overall outcomes. We extended follow‐up of a previously described cohort (n = 69) treated with 4 weekly doses of rituximab and observed durable responses (median time to progression, 30 months; 5‐year survival rate, 66%). Patients achieving a minor response [25–50% immunoglobulin M (IgM) reduction] appeared to do as well as those achieving an objective response (>50% IgM reduction), which suggests that more aggressive or intensive therapy for minor responders is not required. Future studies of Waldenström macroglobulinaemia should report minor responses because they are associated with clinically meaningful benefits. This trial was registered at http://www.clinicaltrials.gov as #NCT00005609.
Perception and practice of child labour among parents of school‐aged children in Ibadan, southwest Nigeria
Authors: Omokhodion F. O. , Uchendu O. C.
Published: September 2009

Background  The problem of child labour has lingered on in many countries because of the complex combination of social, cultural and economic factors involved. Parents play a critical role in child labour as it provides much needed extra income for the family. This study was carried out among parents of school‐aged children in an urban, low‐income community to determine the factors associated with child labour and attitudes to child labour in the community.

Methods  A cross‐sectional study was carried out in an urban community in Ibadan, southwest Nigeria. Questionnaires were administered to parents of school‐aged children.

Results  A total of 473 parents were interviewed. They were aged between 23 and 56 years, mean 37.9 years. Thirty‐nine per cent of parents indicated that they thought their school‐aged children should work. More women than men, those from polygamous homes and those with lower educational status held this view. Reasons given for wanting their children to work were to supplement family income, 45%, to gain experience, 35% and to help in family business, 10%. In all, 236 (50%) respondents reported that their school‐aged children were working. Parental factors associated with practice of child labour were polygamous marriage, low educational status, unskilled or partly skilled occupation and large family size. Seventeen per cent of parents with working children were not satisfied with their children's work conditions and complained of low earnings, long working hours, work on school days and unsafe work environment. Measures suggested to control child labour include addressing the issue of household poverty, public enlightenment about the ills of child labour and free education up to junior secondary level. Enforcement of child labour laws was the least mentioned.

Conclusion  We conclude that control of child labour should be a multifaceted approach involving poverty alleviation, family planning to reduce family size and free, compulsory education up to junior secondary level. Public enlightenment especially for mothers will be of additional benefit.
Evidence of multiple chromosomal inversions in Aedes aegypti formosus from Senegal
Authors: Bernhardt S. A. , Blair C. , Sylla M. , Bosio C. , Black IV W. C.
Published: September 2009

Chromosomal inversions are prevalent in mosquito species but polytene chromosomes are difficult to prepare and visualize in members of the tribe Aedinii and thus there exists only indirect evidence of inversions. We constructed an F1 intercross family using a P1 female from a laboratory strain of Aedes aegypti aegypti (Aaa) and a P1 male Aedes aegypti formosus (Aaf) from a strain collected from south‐eastern Senegal. Recombination rates in the F2 offspring were severely reduced and genotype ratios suggested a deleterious recessive allele on chromosome 3. The F2 linkage map was incongruent in most respects with the established map for Aaa. Furthermore, no increased recombination was detected in F5 offspring. Recombination rates and gene order were consistent with the presence in Aaf of at least four large inversions on chromosome 1, a single small inversion on chromosome 2 and three inversions on chromosome 3.
Homing endonucleases catalyze double‐stranded DNA breaks and somatic transgene excision in Aedes aegypti
Authors: Traver B. E. , Anderson M. A. E. , Adelman Z. N.
Published: September 2009

Aedes aegypti is a major vector of arthropod‐borne viruses such as yellow fever virus and dengue viruses. Efforts to discern the function of genes involved in important behaviours, such as vector competence and host seeking through reverse genetics, would greatly benefit from the ability to generate targeted gene disruptions. Homing endonucleases are selfish elements which catalyze double‐stranded DNA (dsDNA) breaks in a sequence‐specific manner. In this report we demonstrate that the homing endonucleases I‐PpoI, I‐SceI, I‐CreI and I‐AniI are all able to induce dsDNA breaks in adult female Ae. aegypti chromosomes as well as catalyze the somatic excision of a transgene. These experiments provide evidence that homing endonucleases can be used to manipulate the genome of this important disease vector.
Assessment of mitochondrial potential: implications for the correct monitoring of human sperm function
Authors: Amaral A. , Ramalho‐Santos J.
Published: September 2009

Mitochondrial membrane potential (MMP) is an indicator of sperm functionality that can be assessed using specific fluorescent markers. However, the ability of distinct probes to dynamically evaluate sperm MMP has not been determined. In the present study, human sperm samples were independently labelled with MitoTracker Green, MitoTracker Red and JC‐1. The ability of each probe to correctly monitor MMP was determined by incubating sperm with MMP disruptors (KCN, FCCP and valinomycin). Similarly, the effect of distinct fixatives (formaldehyde and methanol) was also tested. The three mitochondrial probes provided similar results, and were able to monitor changes in MMP when sperm had been previously incubated with MMP‐disrupting agents. However, only JC‐1 could, to a small extent, mirror MMP alterations after sperm labelling. Unexpectedly, the three probes were able to stain some pre‐fixed sperm, even though this behaviour was very variable, especially for MitoTrackers. On the other hand, none of the probes was shown to be reliably fixable. Of the three probes tested JC‐1 seems to be the most adequate, nevertheless, the choice of an MMP‐specific probe may depend on the aim of each experimental setting and appropriate controls must always be performed.
Isolation and introgression in the Intermountain West: contrasting gene genealogies reveal the complex biogeographic history of the American pika (Ochotona princeps)
Authors: Galbreath Kurt E. , Hafner David J. , Zamudio Kelly R. , Agnew Kelly
Published: September 2009

Aim We studied the history of colonization, diversification and introgression among major phylogroups in the American pika,Ochotona princeps(Lagomorpha), using comparative and statistical phylogeographic methods. Our goal was to understand how Pleistocene climatic fluctuations have shaped the distribution of diversity at mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) loci in this alpine specialist.

Location North America’s Intermountain West.

Methods We accumulated mtDNA sequence data (c. 560–1700 bp) from 232 pikas representing 64 localities, and sequenced two nuclear introns (mast cell growth factor,c. 550 bp,n = 148; protein kinase C iota,c. 660 bp,n = 139) from a subset of individuals. To determine the distribution of major mtDNA lineages, we conducted a phylogenetic analysis on the mtDNA sequence data, and we calculated divergence times among the lineages using a Bayesian Markov chain Monte Carlo approach. Relationships among nuclear alleles were explored with minimum spanning networks. Finally, we conducted coalescent simulations of alternative models of population history to test for congruence between nDNA and mtDNA responses to Pleistocene glacial cycles.

Results We found that: (1) all individuals could be assigned to one of five allopatric mtDNA lineages; (2) lineages are associated with separate mountain provinces; (3) lineages originated from at least two rounds of differentiation; (4) nDNA and mtDNA markers exhibited overall phylogeographic congruence; and (5) introgression among phylogroups has occurred at nuclear loci since their initial isolation.

Main conclusions Pika populations associated with different mountain systems have followed separate but not completely independent evolutionary trajectories through multiple glacial cycles. Range expansion associated with climate cooling (i.e. glaciations) promoted genetic admixture among populations within mountain ranges. It also permitted periodic contact and introgression between phylogroups associated with different mountain systems, the record of which is retained at nDNA but not mtDNA loci. Evidence for different histories at nuclear and mtDNA loci (i.e. periodic introgression versus deep isolation, respectively) emphasizes the importance of multilocus perspectives for reconstructing complete population histories.
Targeted proteomics using selected reaction monitoring reveals the induction of specific terpene synthases in a multi‐level study of methyl jasmonate‐treated Norway spruce (Picea abies)
Authors: Zulak Katherine G. , Lippert Dustin N. , Kuzyk Michael A. , Domanski Dominik , Chou Tina , Borchers Christoph H. , Bohlmann Jörg
Published: September 2009

Induction of terpene synthase (TPS) gene expression and enzyme activity is known to occur in response to various chemical and biological stimuli in several species of spruce (genus Picea). However, high sequence identity between TPS family members has made it difficult to determine the induction patterns of individual TPS at the protein and transcript levels and whether specific TPS enzymes respond differentially to treatment. In the present study we used a multi‐level approach to measure the induction and activity of TPS enzymes in protein extracts of Norway spruce (Picea abies) bark tissue following treatment with methyl jasmonate (MeJA). Measurements were made on the transcript, protein, enzyme activity and metabolite levels. Using a relatively new proteomics application, selective reaction monitoring (SRM), it was possible to differentiate and quantitatively measure the abundance of several known TPS proteins and three 1‐deoxy‐d‐xylulose 5‐phosphate synthase (DXS) isoforms in Norway spruce. Protein levels of individual TPS and DXS enzymes were differentially induced upon MeJA treatment and good correlation was generally observed between induction of transcripts, proteins, and enzyme activities. Most of the mono‐ and diterpenoid metabolites accumulated with similar temporal patterns of induction as part of the coordinated multi‐compound chemical defense response. Protein and enzyme activity levels of the monoTPS (+)‐3‐carene synthase and the corresponding accumulation of (+)‐3‐carene was induced to a higher fold change than any other TPS or metabolite measured, indicating an important role in the induced terpenoid defense response in Norway spruce.
Availability of essential medicines in Ethiopia: an efficiency‐equity trade‐off?
Authors: Carasso Barbara S. , Lagarde Mylene , Tesfaye Addis , Palmer Natasha
Published: September 2009

Objective  To investigate the availability and cost of essential medicines in health centres in rural Ethiopia, and to explore if the fee waiver system protects patients from having to pay for medicines.

Methods  The study took place in five health centres in rural Ethiopia. Availability and price of selected key essential medicines was established in the budget and special pharmacy of the health centre, as well as private outlets. Information on availability and cost of prescribed drugs was obtained through patient exit‐interviews.

Results  Availability based of essential drugs at facility level was 91% based on a list of selected drugs vs. 84% based on prescriptions filled. However, less than half the prescribed drugs were obtained from the budget pharmacy, and one in six patients was forced to purchase drugs in the private sector, where drugs are roughly twice as expensive. The waiver system did not safeguard against having to pay for medicines.

Conclusion  A revolving drug fund system in Ethiopia seems to improve availability of medicines, and can improve affordability by protecting people from purchasing drugs in the private sector. However, it may result in a parallel system, whereby the poor cannot access drugs if these are not available in the budget pharmacy. Equity is a concern in the absence of an adequate mechanism to protect the poor from catastrophic health expenditure.
Management of children with otitis media: A summary of evidence from recent systematic reviews
Authors: Gunasekera Hasantha , Morris Peter S , McIntyre Peter , Craig Jonathan C
Published: September 2009

Health‐care professionals who manage children are regularly confronted with clinical questions regarding the management of the full spectrum of otitis media: acute otitis media; otitis media with effusion; and chronic suppurative otitis media. Given the variety of potential therapies available, the wide spectrum of middle ear disorders, and the lack of consensus about management strategies, clinicians are in a difficult position when managing these children. In this review, we seek to summarise the current best evidence for answering otitis media management questions by collating existing systematic reviews.
Evaluation of a feasibility study addressing risk factors for childhood obesity through home visits
Authors: Wen Li Ming , De Domenico Maria , Elliott Donna , Bindon Jeni , Rissel Chris
Published: September 2009

Aim:  This pilot study aimed to explore the feasibility of addressing risk factors for childhood obesity through a home‐based early intervention program.

Method:  A pilot study was conducted with 56 first‐time mothers, recruited through the antenatal and delivery units of an inner western Sydney hospital. The study offered five home visits by a community early childhood health nurse during the child's first year of life. At each visit, the intervention was tailored to the appropriate developmental stage of the child. One‐to‐one consultation was provided with a focus on sustained breastfeeding, appropriate introduction of solids, avoiding food rewards and promoting the drinking of water and the use of a cup. Both quantitative and qualitative methods were applied to assess the feasibility and acceptability of the program.

Results:  The results indicate that the program was very well received by the participating mothers, with a retention rate of 95%. Compared with the state population average, the rate of breastfeeding at 12 months was significantly higher (36% vs. 18%, χ2= 8.21, P < 0.01), there was a lower rate of the introduction of solids before 4 months (2% vs. 13%, χ2= 8.73, P < 0.01), and there was a high rate of cup usage at 12 months (98%).

Conclusions:  The early onset of childhood overweight and obesity requires health promotion intervention programs to commence as early as possible. A home‐based intervention through multiple home visits is feasible in addressing the risk factors for childhood obesity.
Immunisation practices in infants born prematurely: Neonatologists' survey and clinical audit
Authors: Crawford Nigel W , Yeo Vivien , Hunt Rod W , Barfield Charles , Gelbart Ben , Buttery Jim P
Published: September 2009

Aim:  To determine Australian neonatologists' recommendations for the immunisation of ex‐preterm infants and compare their actual immunisation status with recommended Australian guidelines.

Methods:  A self‐administered nine‐part questionnaire of current immunisation practices was sent to all Neonatologists in Australia (2006). A complementary retrospective immunisation audit was conducted in two tertiary neonatal units in Melbourne. Hospital records and the Australian Childhood Immunisation Register (ACIR) were reviewed; consenting parents were interviewed and primary care physicians' vaccination records were requested. A random sample of preterm infants born between July 2003 and June 2005 at <32 weeks' gestation were selected.

Results:  (i) Neonatologists Survey: The response rate was 68% and the majority of neonatologists (89%) were aware of the current guidelines, but adherence to them varied from 43% to 79%. One‐fifth of neonatologists personally do not receive annual influenza vaccination; and (ii) Immunisation Audit: Conducted between October 2006‐May 2007 it included: 100 hospital records; 97 ACIR records; 47 parent interviews and 43 primary care vaccination records. Overall vaccination coverage was 90% at 12 months of age. Only 20% (10/50) of infants with chronic lung disease received an influenza vaccination. Vaccines were delayed by greater than one month in 15% of participants for the 2 month DTPa vaccine and 43% at 6 months.

Conclusions:  The neonatologists survey highlighted variable adherence with immunisation guidelines. The audit confirmed preterm infants are frequently experiencing delayed vaccination and recommended additional vaccinations are often not being received. Formulation of strategies to ensure complete and timely immunisation are required, including better utilisation of the ACIR.
Bezold's abscess: A serious complication of otitis media
Authors: McMullan Brendan
Published: September 2009

This report describes a case of Bezold's abscess, a rare complication of mastoiditis, following otitis media. Included is a discussion of mastoiditis and its management.
Impact of mesangial IgA deposits in 14th‐postoperative‐day routine renal allograft biopsies
Authors: KIM Yong‐Soo , CHOI Young Jin , CHOI Bum Soon , PARK Joo Hyun , YANG Chul Woo , KIM Suk Young , BANG Byung Kee
Published: September 2009

SUMMARY:Three hundred fourteen 14th‐postoperative‐day routine renal allograft biopsies were evaluated together with clinical data. Out of 314 biopsies, mesangial IgA deposits were positive in 122 biopsies (39%). According to Banff classification, the rate of acute rejection was significantly lower in mesangial IgA deposit‐positive (IgA(+)) patients (7.4%) than in mesangial IgA deposit‐negative (IgA(‐)) patients (19.7%) on the 14th postoperative day. Thereafter, rate of biopsy‐proven and clinical acute rejection was continuously lower for up to 12 months in IgA(+) patients than in IgA(‐) patients. the detection rate of mesangial IgA deposits was significantly higher in human leucocyte antigen (HLA)‐well‐matched (HLA mismatch number was <3) patients than in HLA‐poorly matched (HLA mismatch number was <3) patients. In HLA‐well‐matched patients, the serum creatinine levels were significantly lower in IgA(+) patients than in IgA(‐) patients after 3 post‐transplant months and up to 1 post‐transplant year. Follow‐up (mean interval: 13 months) allograft biopsies were performed in 34 patients out of 122 IgA(+) patients. In the follow‐up biopsies, initially detected mesangial IgA deposits had disappeared in 22 patients (65%) out of 34 patients. Twelve patients (35%) still had mesangial IgA deposits, and all of them had clinical and pathological findings consistent with IgA nephropathy. Patients with continuous mesangial IgA deposits in the follow‐up biopsies had a better renal function at 1 year and a higher 5‐year graft survival rate compared with patients who lost the initially deposited IgA. the present study demonstrates that long‐lasting mesangial IgA deposits in renal transplants prevent allografts from acute rejection, which leads to better graft outcome.
Darbepoetin alfa: A new erythropoietic drug for the treatment of renal anaemia*
Authors:   Amgen Anaemia Advisory Group
Published: September 2009

SUMMARY: Darbepoetin alfa (Aranesp®, Amgen Ltd) is a long‐acting, hyperglycosylated recombinant human erythropoietin (r‐HuEPO; epoetin) analogue, developed for the treatment of anaemia in patients with chronic kidney disease (CKD, i.e. end‐stage renal failure or progressive renal impairment). Based on previously published European guidelines, this review article presents key recommendations for the use of darbepoetin alfa in Australasian clinical practice.

Darbepoetin alfa is expected to be a valuable alternative therapeutic agent for the management of renal anaemia. Clinical data demonstrate that: Once‐weekly administration of darbepoetin alfa ‐ whether by subcutaneous (s.c.) or intravenous (i.v.) injection ‐ is as effective as epoetin therapy, administered two or three times per week; patients receiving once‐weekly doses of epoetin can be switched to darbepoetin alfa, once every 2 weeks; target haemoglobin (Hb) concentrations can be successfully maintained in patients switched from epoetin therapy to less frequently administered doses of darbepoetin alfa (administration once every 2 weeks is sufficient for some patients); and darbepoetin alfa has a similar safety profile to epoetin. In addition to addressing a number of practical considerations relating to the use of darbepoetin alfa in clinical practice, this article also highlights principal findings from several key clinical studies.
A NEW THIN ENDOSCOPIC METHOD OF TRANSANAL DRAINAGE TUBE INSERTION FOR ACUTE COLONIC OBSTRUCTION DUE TO COLORECTAL CANCER
Authors: Ohnita Ken , Shikuwa Saburo , Isomoto Hajime , Yamaguchi Naoyuki , Okamoto Kenta , Nishiyama Hitoshi , Fukuda Eiichiro , Nakamura Takashi , Mizuta Yohei , Kohno Shigeru
Published: September 2009

Aim:  Insertion of a transanal drainage tube is effective in the management of obstructing colorectal cancer. We devised a new method of inserting the transanal drainage tube safely and quickly using a thin endoscope.

Methods:  Sixteen patients (seven men and nine women) with obstructive left‐sided colorectal cancer were treated by inserting a transanal drainage tube using a thin endoscope. We inserted a transanal drainage tube for 32 patients (21 men and 11 women) with left‐sided colorectal cancer using the conventional method.

Results:  Drainage tube placement by the conventional method was successful in 29 (90.6%) of 32 patients, while via the new method, it was successful in all 16 patients without major complications. Moreover, median insertion time was significantly shortened (34 minutes for the new method compared with 42 minutes for the conventional method).

Conclusion:  Management of acute colorectal obstruction by transanal drainage tube insertion using the thin endoscope was effective and safe.
SLOW GROWING FLAT‐TYPE PRIMARY MALIGNANT MELANOMA OF THE ESOPHAGUS TREATED WITH CAP‐ASSISTED EMR
Authors: Miyatani Hiroyuki , Yoshida Yukio , Ushimaru Shinya , Sagihara Noriyoshi , Yamada Shigeki
Published: September 2009

We report a rare case of flat‐type primary malignant melanoma of the esophagus treated with endoscopic mucosal resection (EMR). A 64‐year‐old woman was referred for examination of a small pigmented lesion located in the mid esophagus. On endoscopy, the lesion exhibited almost no change in size over the year. Cap‐assisted EMR was performed en bloc. The histopathological findings showed atypical melanocyte proliferation in the basal layer, spindle cells, and epithelioid cell proliferation with nuclear enlargement and a few mitotic figures. Histopathological examination confirmed the diagnosis of primary malignant melanoma. Immunostaining for S‐100 protein and HMB‐45 antibody were positive, and the Ki‐67 index was low. The patient was discharged without additional surgical resection and/or chemotherapy. The patient had no symptoms and no signs of recurrence 20 months after EMR. There has been no report on a slow growing esophageal melanoma. It is difficult to estimate the malignant behavior of this case.
ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL DUODENAL NEOPLASMS
Authors: Honda Tetsuro , Yamamoto Hironori , Osawa Hiroyuki , Yoshizawa Mitsuyo , Nakano Hidetoshi , Sunada Keijiro , Hanatsuka Kazunobu , Sugano Kentaro
Published: September 2009

Endoscopic submucosal dissection (ESD) has emerged as a novel technique for achieving en bloc resection for superficial neoplasms limited to the mucosa. ESD was originally developed in Japan as a method of endoscopic resection of superficial gastric cancers. In our hospital, ESD has been used concurrently in other parts of the gastrointestinal tract, including the esophagus and colorectum from the beginning of its development. However, ESD in the duodenum is considered more challenging than other parts. From August 2005 to March 2008, a total of 15 superficial duodenal neoplastic lesions in 14 patients were treated with endoscopic resection. Of these, nine underwent ESD. We report our experience with duodenal ESD with a combination of ST hood and hook knife.
Hypospadias: risk factor patterns and different phenotypes
Authors: Brouwers Marijn M. , Van Der Zanden Loes F.M. , De Gier Robert P.E. , Barten Evert J. , Zielhuis Gerhard A. , Feitz Wouter F.J. , Roeleveld Nel
Published: September 2009

Study Type – Aetiologic (case‐referent) Level of Evidence 2a

OBJECTIVE

To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case‐referent study in which a distinction was made between different phenotypes.

PATIENTS AND METHODS

Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression.

RESULTS

Low birth weight, being a twin or triplet, mother being a diethylstilbestrol‐daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5–24.1) and 9.0 (3.1–26.0), but not for the proximal type at 1.8 (0.2–14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4–24.2) compared with distal and middle hypospadias at 2.6 (1.4–5.0) and 2.3 (0.8–6.5). There were similar estimates for pre‐eclampsia.

CONCLUSION

These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development.
The West Midlands Bladder Cancer Prognosis Programme: rationale and design
Authors: Zeegers Maurice P. , Bryan Richard T. , Langford Carolyn , Billingham Lucinda , Murray Paul , Deshmukh Neeta S. , Hussain Syed , James Nick , Wallace D. Michael A. , Cheng K.K.
Published: September 2009

Study Type – Prognosis (inception cohort) Level of Evidence 1b

OBJECTIVE

To describe the rationale and design of the Bladder Cancer Prognosis Programme (BCPP), and to demonstrate the capability of this design.

METHODS

There is a need to understand the determinants of bladder cancer to help reduce recurrence, progression, morbidity, mortality and related costs. We previously showed that lifestyle factors are important for determining the risk of bladder cancer, but little is known about their importance in determining the risk of recurrence or progression after diagnosis. Also, histopathological factors alone provide only crude prognostication; the analysis of molecular markers represents a method for refinement but research in this area has not been useful in informing therapeutic decisions or prognostication. The BCPP is a prospective longitudinal cohort study of all patients with newly diagnosed bladder cancer within the West Midlands (UK), investigating the influence of lifestyle factors on recurrence and progression, health‐related quality of life, the predictive effect of a panel of molecular markers on recurrence or progression, and the establishment of Europe’s largest comprehensive bladder cancer bio‐repository. It also incorporates the first randomized clinical trial on the efficacy of selenium and vitamin E on bladder cancer. The numbers and proportions of eligible patients recruited, questionnaires completed and specimens obtained were all recorded.

RESULTS

Since December 2005, 771 patients have been recruited (68% of eligible patients) and of these, 331 are currently being followed up by questionnaires. We have obtained blood, urine and tumour tissues from 92%, 80% and 80% of patients, respectively.

CONCLUSIONS

The design of the BCPP has allowed this study to be incorporated into routine clinical work throughout the West Midlands, achieving high levels of recruitment, and data and specimen collection. This might represent a model for the future investigation of urological and other malignancies.
Abnormal protein expression in the corpus cavernosum impairs erectile function in type 2 diabetes
Authors: Chiou Wen‐Fei , Liu Hui‐Kang , Juan Chi‐Wen
Published: September 2009

Study Type – Aetiology (case control) Level of Evidence 3b

OBJECTIVE

To investigate the changes in corporal relaxation, intracavernous pressure (ICP) and associated protein expression that control normal erectile function in rats with type 2 diabetes (T2D), as this disease is part of the ‘metabolic syndrome’ associated with a high rate of erectile dysfunction (ED) in men, resulting from failure of corpus cavernosum‐mediated processes.

MATERIALS AND METHODS

T2D was induced in rats by feeding them with a high‐fat diet (HFD) followed by an injection with low‐dose streptozotocin (STZ); they were then compared with rats that received a normal diet (ND).

RESULTS

Hyperglycaemia and dyslipidaemia were induced in HFD + STZ rats, suggesting that T2D was established. The rats with T2D had associated ED, as both nonadrenergic noncholinergic‐mediated corporal relaxation and increased ICP by cavernous nerve stimulation were significantly attenuated compared to the ND group. Western blot analysis revealed diabetes‐associated lower expression of endothelial and neuronal nitric oxide synthase (e and nNOS), and cGMP‐dependent protein kinase (PKG)‐1α/β expression in penile tissue than in the ND group. Contrary to the proteins that regulate corporal relaxation, there were relatively high levels of RhoA/Rho kinase receptor 1 (ROCK1) and ET‐A receptor (ETAR) in T2D rats. However, the expressed level of phosphodiesterase‐5 and insulin‐like growth factor binding protein 3 was not altered significantly in response to T2D.

CONCLUSION

Decreased expression of certain proteins that mediate the relaxant mechanism, associated with increased expression of certain proteins that mediate contractile mechanisms, might be important in the development of T2D‐associated ED. In particular, down‐regulated eNOS/nNOS/PKG1 as well as up‐regulated ETAR/RhoA/ROCK1 might participate in the aetiology of ED in T2D.
Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging
Authors: Pierorazio Phillip M. , Ferrucci Luigi , Kettermann Anna , Longo Dan L. , Metter E. Jeffrey , Carter H. Ballentine
Published: September 2009

Study Type – Prognosis (inception cohort) Level of Evidence 1b

OBJECTIVE

To evaluate the relationship between testosterone levels and the development of high‐risk prostate cancer, by prospectively examining serum androgen concentrations in a well‐studied cohort, as the role of testosterone in prostate cancer progression is debated.

PATIENTS AND METHODS

The study comprised 781 men in the Baltimore Longitudinal Study of Aging who had sex steroid measurements before a diagnosis of prostate cancer, or at their last visit for those without cancer (no cancer, 636; cancer, not high risk, 109; cancer, high risk, 36). High‐risk cancer was defined as death from prostate cancer, a prostate specific antigen (PSA) level of ≥20 ng/mL at diagnosis, or a Gleason score of ≥8. The hazard ratio (HR) of high‐risk disease was determined using a Cox proportional hazards regression model with simple updating, and risk rates were stratified by age and tercile for androgens of interest based on the proportional hazards analyses.

RESULTS

The likelihood of high‐risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged >65 years (HR 2.07, 95% confidence interval, CI, 1.01–4.23; P = 0.047); the likelihood for men aged ≤65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35–2.6; P = 0.9). The risk rate per person‐years increased from lowest to highest tercile of FTI for the oldest men (age >70 years) but this trend was not apparent among younger men.

CONCLUSION

Higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. These data highlight the importance of prospective trials to insure the safety of testosterone‐replacement therapy.
Structural analysis of the corpora cavernosa in patients with ischaemic priapism
Authors: Costa Waldemar S. , Felix Bruno , Cavalcanti Andre G. , Medeiros Jr Jorge , Sampaio Francisco J.
Published: September 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To evaluate, using quantitative and qualitative methods, the changes in the corpora cavernosa of patients with ischaemic priapism.

PATIENTS AND METHODS

We obtained samples of corpora cavernosa from seven patients with ischaemic priapism (mean age 38 years, range 28–44) who had a cavernous‐glandular shunt. The control tissues were fragments of corpora cavernosa obtained from autopsies of seven age‐matched men who died from causes unrelated to the urogenital tract. Histochemical and immunohistochemical techniques were used to assess and quantify the extracellular matrix and smooth muscle fibres. The volumetric density of smooth muscle, elastic fibres and collagen were determined in corpora cavernosa.

RESULTS

From the stereological analysis the mean (sd) values of volumetric density were: for collagen, control 34.76 (4.64), priapism 39.64 (2.91) (P = 0.002); elastic system fibres, controls 28.10 (2.85), priapism 36.10 (3.06) (P = 0.001); smooth muscle fibres, controls 43.37 (4.96), priapism 26.48 (5.00) (P < 0.001). There were significantly more fibrous elements of the connective tissue and significantly fewer smooth muscle fibres in the corpora cavernosa of patients with ischaemic priapism than in controls.

CONCLUSION

Ischaemic priapism is associated with early and significant changes in the components of the extracellular matrix and smooth muscle fibres of the corpora cavernosa. This could explain the frequent occurrence of erectile dysfunction found in patients with ischaemic priapism.
Retroperitoneoscopic partial adrenalectomy for small adrenal tumours (≤1 cm): the Ruijin clinical experience in 88 patients
Authors: Wang Xiao‐jing , Shen Zhou‐jun , Zhu Yu , Zhang Rong‐ming , Shun Fu‐kang , Shao Yuan , Rui Wen‐bin , He Wei
Published: September 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To present our experience of retroperitoneoscopic partial adrenalectomy (RPA) for small adrenal tumours, as with modern imaging methods small adrenal lesions are being diagnosed more commonly, and retroperitoneoscopic adrenal surgery for small adrenal tumours (≤1 cm) can be challenging.

PATIENTS AND METHODS

We retrospectively reviewed the records of 389 consecutive retroperitoneoscopic adrenalectomies from September 2005 to December 2008, 88 of which were small adrenal tumours and treated by RPA. Ultrasonography and computed tomography (CT) were used in all patients before RPA, and magnetic resonance imaging or positron emission tomography/CT in some patients. We used RPA for adrenal tumours and total adrenalectomy for adrenal cancer. During the surgery, the internal part of the adrenal gland close to the retroperitoneum was freed first, and the whole adrenal tissue was dissected completely. The preoperative imaging was important in these procedures.

RESULTS

There were no deaths; conversions to open surgery were necessary in four patients (4.5%), the reasons being a missing target in two, massive haemorrhage caused by central adrenal vein injury in one, and severe adhesion in one. The mean (range) size of the adrenal tumours was 0.7 (0.5–1.0) cm, including 69 aldosterone‐producing adenomas, 11 nonfunctional adrenal adenomas, three Cushing syndrome, two phaeochromocytomas, two myelolipomas and one melanoma. The operative duration in the initial 38 cases was significantly longer than that in the subsequent 50 (P < 0.01). However, there was no significant correlation between estimated blood loss and the number of procedures. Tumour size did not correlate with estimated blood loss and operative duration. There was no significant correlation between body mass index and operative duration.

CONCLUSION

RPA is a safe, effective and minimally invasive therapeutic option for patients with small adrenal tumours. With improved operative technique the RPA has been completed in more quickly. Freeing the internal part of the adrenal gland close to the retroperitoneum first, and exploring the whole adrenal tissue during surgery are the key points of RPA. The location of the small adrenal tumour can be different from that shown on imaging before surgery, and the abnormality of the adrenal gland should be considered.
Renal cell carcinoma with retro‐aortic renal vein thrombus: a case series
Authors: Marsh Howard , Cranston David , Sullivan Mark
Published: September 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To present three cases of tumour thrombus in the retro‐aortic renal vein (RARV) arising from left renal cell carcinomas (RCCs), a very rare event (<1:1000–2000 per case) and to discuss the embryological, radiological and surgical aspects of this anomaly.

PATIENTS AND METHODS

Three cases of RCC with RARV thrombus presented in a 1‐month period at one institution.

RESULTS

All three cases were identified before surgery by computed tomography (CT) urograms and had a successful nephrectomy.

CONCLUSION

RCC in the presence of RARVs is rare but can be identified on CT urogram. At nephrectomy, a midline laparotomy or full ‘rooftop incision’ is recommended, and any attempt to mobilize the kidney before dealing with the renal pedicle should be avoided.
The Development of Emotion Recognition in Individuals With Autism
Authors: Rump Keiran M. , Giovannelli Joyce L. , Minshew Nancy J. , Strauss Mark S.
Published: September 2009

Emotion recognition was investigated in typically developing individuals and individuals with autism. Experiment 1 tested children (5–7 years, n = 37) with brief video displays of facial expressions that varied in subtlety. Children with autism performed worse than the control children. In Experiment 2, 3 age groups (8–12 years, n = 49; 13–17 years, n = 49; and adults n = 45) were tested on the same stimuli. Whereas the performance of control individuals was best in the adult group, the performance of individuals with autism was similar in all age groups. Results are discussed with respect to underlying cognitive processes that may be affecting the development of emotion recognition in individuals with autism.