bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male-Specific Hepatic Bcl6: Growth Hormone-Induced Block of Transcription Elongation in Females and Binding to Target Genes Inversely Coordinated with STAT5
Authors: Meyer Rosana D. , Laz Ekaterina V. , Su Ting , Waxman David J. 
Published: October 2009

AbstractThe transcriptional repressor Bcl6 is a male-specific rat liver gene product and one of 24 early GH-response genes encoding DNA-binding proteins. Presently, the sex specificity of Bcl6 was shown to emerge at puberty, when hepatic Bcl6 mRNA was induced in males and repressed in females by the female plasma GH profile. Hepatic Bcl6 mRNA was increased to near-normal male levels in hypophysectomized females and was extinguished in intact males given a continuous GH infusion (female-like GH pattern). Bcl6 was also repressed in adult male somatostatin-deficient mice, where plasma GH profiles are female like. Hepatic Bcl6 RNA was rapidly down-regulated by GH pulse treatment, both in hypophysectomized male rats and in primary rat hepatocytes. Bcl6 was substantially induced in female mice deficient in hepatic signal transducer and activator of transcription (STAT)5a/STAT5b, suggesting that these STAT transcriptional mediators of GH signaling repress Bcl6. Indeed, STAT5 was bound to Bcl6 STAT5-binding region-B, previously associated with Bcl6 repression, in both male and female liver chromatin. STAT5 also bound to Bcl6 region-A in male chromatin but only during a plasma GH pulse. Analysis of primary transcripts (heterogenous nuclear RNA) across the Bcl6 gene revealed a novel mechanism of GH-dependent sex specificity, with two apparent blocks in Bcl6 transcription elongation seen in female liver and in continuous GH-treated male liver, one early in intron 4 and one in exon 5, which together reduced transcription beyond exon 5 more than 300-fold. Finally, Bcl6 was bound to a subset of STAT5-binding sites in male liver chromatin, including a Socs2 STAT5-binding site where Bcl6 binding increased substantially between plasma GH pulses, i.e. when STAT5 binding was low. Bcl6 and STAT5 binding are thus inversely coordinated by the endogenous pulses of pituitary GH release, suggesting this male-specific transcriptional repressor modulates hepatic GH signaling to select STAT5 target genes.
Orthotopic Neobladder versus Ileal Conduit Urinary Diversion after Cystectomy – A Quality-of-Life Based Comparison
Authors: Philip Joe , Manikandan Ramaswamy , Venugopal Suresh , Desouza John , Javlé Pradip M 
Published: October 2009

INTRODUCTION Radical cystectomy remains the gold standard in treatment of muscle invasive bladder cancer. Evolution of pathological guidelines has empowered centres to offer orthotopic substitution (OBS) to patients undergoing radical cystectomy. We compared health-related quality of life (HRQoL) between patients who underwent OBS or ileal conduit urinary diversion (ICD) following radical cystectomy. PATIENTS AND METHODS A total of 57 patients who underwent cystectomy were assessed pre-operatively using Karnofsky performance scale (KPS). Of these, 52 patients (28 OBS and 24 ICD) who responded to a postal questionnaire consisting of SF-36 and a functional index questionnaire were included. RESULTS Median age of patients was 70 years. Pre-operative KPS scores were similar. All eight HRQoL scales were favourable in both groups. OBS patients had significantly better physical functioning. In the cohort, 42% of men with OBS and 25% of diversions could maintain an erection to varying degrees. Of the OBS patients, 85% were continent with two patients reporting reduced QoL with pad usage. Of ICD patients, 63% felt less complete and 42% were embarrassed due to the stoma, with 58% apprehensive of stomal leakage. Of OBS patients, 96% had significant relationships and a more active life-style. CONCLUSIONS In a similar age-group population, there was no significant difference in most QoL indices but body image issues persist in ICD patients. OBS patients had significantly better physical function, continuing to have a more active life-style. They attained urethral voiding with good continence. A detailed discussion of long-term functional outcome would engender a realistic expectation allowing better adaptation.
The Evolution of a Hand Day-Surgery Unit
Authors: Dillon CK , Chester DL , Nightingale Peter , Titley OG 
Published: October 2009

INTRODUCTION Following the merger of two major units to form a regional centre for plastic surgery in the West Midlands, acute hand surgery referrals reached overwhelming proportions. This study describes audits performed at three time points. The first highlighted the extent of in-patient delay and was instrumental in the subsequent development of a dedicated hand trauma day-case unit. PATIENTS AND METHODS Data were collected on 77 patients in June 2002, 109 patients in November 2003 and 90 patients in November 2004. The day-case unit opened on 1 November 2003. RESULTS The number of bed-days per patient fell from 2.63 to 1.34 (P < 0.001) over the study period. In November 2004, 51% of patients received a day-case procedure. Importantly, if admission was required at initial presentation, the delay to theatre reduced from 1.5 bed-days per patient in June 2002 to 0.6 in November 2004. Overall, the in-patient delay was significantly reduced (P < 0.001) but time from presentation to theatre was not significantly affected (P = 0.119). CONCLUSIONS This series of audits confirmed that a significant number of acute hand injuries are suitable for day-case procedures and that simple audit can lead to a significant change in service provision. Improvements were demonstrated in reduced in-patient delay and total stay. We hope that other units find our experience useful given that it may be possible to apply this approach to other forms of ambulatory trauma.
Introduction of a Day-Case Laparoscopic Cholecystectomy Service in the UK: A Critical Analysis of Factors Influencing Same-Day Discharge and Contact with Primary Care Providers
Authors: Briggs CD , Irving GB , Mann CD , Cresswell A , Englert L , Peterson M , Cameron IC 
Published: October 2009

INTRODUCTION The objective of this study was to determine the safety and acceptability of the implementation of a day-case laparoscopic cholecystectomy (LC) service in a large UK teaching hospital, and analyse factors influencing contact with primary care providers. Wide-spread introduction of day-case LC in the UK is a major target of healthcare providers. However, few centres have reported their experience. In the US, out-patient surgery for LC has been reported, though many groups have utilised 24-h observation units to facilitate discharge. Concerns remain amongst surgeons regarding the feasibility and acceptability of the introduction of day-case LC in the UK. PATIENTS AND METHODS Comprehensive care and operative data were prospectively collected on the first 106 consecutive day-case procedures in our hospital. Postoperative recovery was monitored by telephone questionnaire on days 2, 5 and 14, including complications, satisfaction and general practitioner consultation. RESULTS A total of 106 patients were admitted for day-case LC, of whom 84% were discharged on the day of surgery. Patient satisfaction rate was 94% in both the successful day-case and the admitted patients. Mean operation time was 62 min, with an average total stay on the day-care unit of 426 min. Training-grade surgeons performed 31% of operations. Both the re-admission rate after surgery and rate of conversion to open surgery were 2%. Advice from primary healthcare providers was sought by 33% of patients within the first 14 postoperative days. CONCLUSIONS Introduction of day-case LC in the UK is feasible and acceptable to patients. The potential burden to primary care providers needs further study.
Operative Mortality, Blood Loss and the Use of Pringle Manoeuvres in 526 Consecutive Liver Resections
Authors: Lordan Jeffrey T , Worthington Tim R , Quiney Nial , Fawcett William J , Karanjia Nariman D 
Published: October 2009

INTRODUCTION Centres with high volumes of high-risk surgery have significantly better outcomes than low-volume centres for pancreatic resection, oesophagectomy and pelvic exenteration. However, this has not to date been conclusively demonstrated for hepatic resection. With increased experience, operative practice can change. The use of the Pringle manoeuvre reduced substantially over a 12-year period in a single centre as it was felt anecdotally that its use increased the incidence of hepatic insufficiency and operative mortality. This study was designed to review 12 years of experience in a single hepatobiliary centre PATIENTS AND METHODS Data regarding 526 consecutive liver resections were prospectively recorded and retrospectively analysed in a high-volume referral unit over a 12-year period. Patients' demographics, operative mortality and morbidity were analysed on an annual basis. RESULTS Overall peri-operative mortality was 1.9%. Operative mortality in the first 6 years compared to the latter 6 years was 4.1% and 1.2%, respectively (P = 0.13). The morbidity rate was 26.8% and 20.3% in the first and second halves of the study, respectively (P = 0.15). With increased experience, intra-operative blood loss and patients receiving blood transfusions decreased (P = 0.047 and 0.03, respectively) while the number of intra-operative Pringle manoeuvres also decreased (P < 0.0001). Hospital stay decreased significantly over the 12 years (P = 0.049). CONCLUSIONS High-volume centres are the safest environment for hepatic resection. With increased experience, it may be possible to reduce the intra-operative use of the Pringle manoeuvre without increasing the intra-operative blood loss. This may be associated with a decrease in hepatic insufficiency and peri-operative mortality.
Penetrating Missile Injuries During the Iraqi Insurgency
Authors: Ramasamy A , Harrisson SE , Stewart MPM , Midwinter M 
Published: October 2009

INTRODUCTION Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict. PATIENTS AND METHODS Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq. RESULTS Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident. CONCLUSIONS The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.
Laparoscopic Colorectal Surgery: Summary of the Current Evidence
Authors: Aly Emad H 
Published: October 2009

INTRODUCTION Laparoscopic colectomy has not been accepted as quickly as laparoscopic cholecystectomy. This is because of its steep learning curve, concerns with oncological outcomes, lack of randomised controlled trials (RCTs) and initial reports on port-site recurrence after curative resection. The aim of this review is to summarise current evidence on laparoscopic colorectal surgery. PATIENTS AND METHODS Review of literature following Medline search using key words ‘laparoscopic’, ‘colorectal’ and ‘surgery’. CONCLUSIONS Laparoscopic colorectal surgery proved to be safe, cost-effective and with improved short-term outcomes. However, further studies are needed to assess the role of laparoscopic rectal cancer surgery and the value of enhanced recovery protocols in patients undergoing laparoscopic colorectal resections.
Microsystem for Isolation of Fetal DNA from Maternal Plasma by Preparative Size Separation
Authors: Hahn Thomas , Drese Klaus S , O'Sullivan Ciara K 
Published: October 2009

Abstract
Background: Routine prenatal diagnosis of chromosomal anomalies is based on invasive procedures, which carry a risk of approximately 1%–2% for loss of pregnancy. An alternative to these inherently invasive techniques is to isolate fetal DNA circulating in the pregnant mother’s plasma. Free fetal DNA circulates in maternal plasma primarily as fragments of lengths &lt;500 bp, with a majority being &lt;300 bp. Separating these fragments by size facilitates an increase in the ratio of fetal to maternal DNA.
Methods: We describe our development of a microsystem for the enrichment and isolation of cell-free fetal DNA from maternal plasma. The first step involves a high-volume extraction from large samples of maternal plasma. The resulting 80-μL eluate is introduced into a polymeric microsystem within which DNA is trapped and preconcentrated. This step is followed by a transient isotachophoresis step in which the sample stacks within a neighboring channel for subsequent size separation and is recovered via an outlet at the end of the channel.
Results: Recovered fractions of fetal DNA were concentrated 4–8 times over those in preconcentration samples. With plasma samples from pregnant women, we detected the fetal SRY gene (sex determining region Y) exclusively in the fragment fraction of &lt;500 bp, whereas a LEP gene (leptin) fragment was detected in both the shorter and longer recovery fractions.
Conclusions: The microdevice we have described has the potential to open new perspectives in noninvasive prenatal diagnosis by facilitating the isolation of fetal DNA from maternal plasma in an integrated, inexpensive, and easy-to-use microsystem.
Utility of Urine Myoglobin for the Prediction of Acute Renal Failure in Patients with Suspected Rhabdomyolysis: A Systematic Review
Authors: Rodríguez-Capote Karina , Balion Cynthia M , Hill Stephen A , Cleve Richard , Yang Lufang , El Sharif Adell 
Published: October 2009

AbstractBackground: Urine myoglobin continues to be used as a marker of rhabdomyolysis, particularly to assess risk of developing acute renal failure and evaluate treatment success. We sought to determine the predictive validity of urine myoglobin (uMb) for acute renal failure (ARF) in patients with suspected rhabdomyolysis.Methods: We performed a broad systemic review of the literature from January 1980 to December 2006 using the search terms myoglobin$ AND (renal OR ARF OR kidney). Only primary studies published in English where uMb measurement was related to ARF were included.Results: Of 1602 studies screened, 52 met all selection criteria. The studies covered a wide spectrum of etiologies for rhabdomyolysis, dissimilar diagnostic criteria for ARF and rhabdomyolysis, and various methods of uMb measurement and were mostly case series (n = 32). There was poor reporting on the uMb method, and 17 studies failed to provide any information about the method. The reporting of clinical criteria for ARF with respect to timing, description, performance, and interpretation also lacked adequate detail for replication. Eight studies (total 295 patients) had data for 2-by-2 tables. Sensitivity of the uMb test was 100% in 5 of the 8 studies, specificity varied widely (15% to 88%), and CIs around these measures were high. Pooling of data was not possible because of study heterogeneity.Conclusions: There is inadequate evidence evaluating the use of uMb as a predictor of ARF in patients with suspected rhabdomyolysis.
Healthy Individuals Carrying the PCSK9 p.R46L Variant and Familial Hypercholesterolemia Patients Carrying PCSK9 p.D374Y Exhibit Lower Plasma Concentrations of PCSK9
Authors: Humphries Steve E , Neely R Dermot G , Whittall Roslyn A , Troutt Jason S , Konrad Robert J , Scartezini Marileia , Li Ka Wah , Cooper Jackie A , Acharya Jayshree , Neil Andrew 
Published: October 2009

AbstractBackground: We measured plasma PCSK9 concentrations in healthy men with a PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function variant (p.R46L), in statin-treated patients with a clinical diagnosis of familial hypercholesterolemia (FH) and carrying a PCSK9 gain-of-function mutation (p.D374Y), and in statin-treated patients with FH due to different genetic causes.Methods: PCSK9 was measured with a previously described ELISA.Results: In 81 healthy middle-aged Caucasian men, the PCSK9 concentration was significantly associated with the concentrations of total cholesterol (r = 0.42; P &lt; 0.0001), LDL cholesterol (r = 0.34; P = 0.01), and triglycerides (r = 0.25; P = 0.02). In p.R46L carriers, mean (SD) concentrations of PCSK9 were 15% lower than in RR individuals [65.5 μg/L (21.6 μg/L) vs 77.5 μg/L (18.2 μg/L); P = 0.03]. In patients with the p.D374Y variant (n = 7), the mean PCSK9 concentration was significantly lower than in the combined group of patients with an LDLR (low density lipoprotein receptor) mutation (n = 25), an APOB [apolipoprotein B (including Ag(x) antigen)] variant encoding p.R3527Q (n = 6), or no detectable mutation (n = 14) [96.4 μg/L (42.5 μg/L) vs 151.6 μg/L (69.6 μg/L); P = 0.02]. Two of the 14 patients with no mutation had PCSK9 concentrations below the mean for p.D374Y carriers; sequencing of the PCSK9 gene and promoter revealed no mutations. Among 409 FH patients, we identified 6 carriers of the promoter variant −287G&gt;A (1.5%), a frequency similar to that (1.0%) previously reported for 2772 healthy men in the UK. In neither group was the −287G&gt;A variant associated with differences in lipid traits.Conclusions: The loss-of-function p.R46L variant is associated with the expected lower concentrations of circulating PCSK9; the gain-of-function p.D374Y mutation is also associated with lower concentrations, presumably because of the higher affinity of this variant for the LDL receptor and its more rapid clearance. In treated FH patients, a low plasma PCSK9 concentration does not appear to be a useful screening tool for identifying novel PCSK9 mutations.
The sensory-motor theory of semantics: Evidence from functional imaging
Authors: Noppeney Uta 
Published: October 2009

AbstractThis review discusses the contributions of functional imaging (fMRI/PET) to our understanding of how semantic concepts are represented and processed in the human brain. The sensory-motor theory of semantic memory suggests that semantic processing relies on reactivation of sensory-motor representations that were involved in perception and action. More specifically, it attributes an apparent category-specific (e.g. tool vs. animals) organization of semantics to anatomical segregation for different semantic features (e.g. action vs. visual). Within this framework, we will review functional imaging evidence that semantic processing of tools and actions may rely on activations within the visuo-motor system.
Technical details influence the diagnostic accuracy of the 1 μg ACTH stimulation test
Authors: Wade Matthew , Baid Smita , Calis Karim , Raff Hershel , Sinaii Ninet , Nieman Lynnette 
Published: October 2009

ObjectiveTo examine the factors causing inadequate cortisol responses to the 1 μg ACTH stimulation test.DesignRandom test assignment (by age and gender) at 0800 or 1600 h.MethodsWe recruited 20 healthy adults to each of the three age groups (<40 years, 40–55 years, and >55 years; half females in each group). ACTH stimulation tests were performed in an outpatient clinic at the NIH Clinical Research Center. Plasma cortisol was measured just before, and 30 and 60 min after the administration of 1 μg ACTH (1–24). The ACTH concentration in diluted and administered solutions was measured.ResultsTwenty-five volunteers (19 at 1600 h) had a subnormal cortisol response (peak cortisol 10.4–17.5 μg/dl), using a criterion <18 μg/dl (497 nmol/l), for a specificity of 58% (confidence interval (CI) 45–71%). Afternoon testing had a significant impact on failure rates (odds ratio 6.98, CI 2.17–22.43), while gender and age did not. The stock solution contained 1 μg ACTH, but after administration through tubing it contained only 0.5–0.8 μg.ConclusionsThe high rate of abnormal results, especially in the afternoon, and loss of ACTH through tubing suggest that morning testing and minimal tubing should be adopted to avoid an inappropriate diagnosis of adrenal insufficiency. Earlier time points and standardized protocols would facilitate comparison of studies.
Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery?
Authors: Eller-Vainicher Cristina , Morelli Valentina , Salcuni Antonio Stefano , Torlontano Massimo , Coletti Francesca , Iorio Laura , Cuttitta Antonello , Ambrosio Angelo , Vicentini Leonardo , Carnevale Vincenzo , Beck-Peccoz Paolo , Arosio Maura , Ambrosi Bruno , Scillitani Alfredo , Chiodini Iacopo 
Published: October 2009

ObjectiveFew data are available regarding the need of steroid substitutive therapy after unilateral adrenalectomy for adrenal incidentaloma (AI). It is unknown whether, before surgery, the hypothalamic–pituitary–adrenal (HPA) axis secretion parameters can predict post-surgical hypocortisolism.AimThis study aimed to evaluate whether, in AI patients undergoing unilateral adrenalectomy, post-surgical hypocortisolism could be predicted by the parameters of HPA axis function.DesignProspective, multicenter.MethodsA total of 60 patients underwent surgical removal of AI (surgical indication: 29 subclinical hypercortisolism (SH); 31 AI dimension). Before surgery, SH was diagnosed in patients presenting at least three criteria out of urinary free cortisol (UFC) levels>60 μg/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 μg/dl, ACTH levels<10 pg/ml, midnight serum cortisol (MSC)>5.4 μg/dl.Two months after surgery, HPA axis function was assessed by low dose ACTH stimulation test or insulin tolerance test when needed: 39 patients were affected (Group B) and 21 were not affected (Group A) with hypocortisolism. The accuracy in predicting hypocortisolism of pre-surgical HPA axis parameters or their combinations was evaluated.ResultsThe presence of >2 alterations among 1 mg-DST>5.0 μg/dl, ACTH<10 pg/ml, elevated UFC and MSC has the highest odds ratio (OR) for predicting post-surgical hypocortisolism (OR 10.45, 95% confidence interval, CI 2.54–42.95, P=0.001). Post-surgical hypocortisolism was predicted with 100% probability by elevated UFC plus MSC levels, but not ruled out even in the presence of the normality of all HPA axis parameters.ConclusionPost-surgical hypocortisolism cannot be pre-surgically ruled out. A steroid substitutive therapy is indicated after unilateral adrenalectomy for SH or size of the adenoma.