bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Diabetes Causes Mitochondrial Dysfunction and Meiotic Defects in Murine Oocytes
Authors: Wang Qiang , Ratchford Ann M. , Chi Maggie M.-Y. , Schoeller Erica , Frolova Antonina , Schedl Tim , Moley Kelle H. 
Published: July 2009

Abstract
The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one-cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure, and the quantitative analysis of mitochondrial DNA copy number demonstrated an increase. The levels of ATP and tricarboxylic acid cycle metabolites in diabetic oocytes were markedly reduced compared with controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in nondisjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.
General Paediatric Surgical Provision of Percutaneous Endoscopic Gastrostomy in a District General Hospital – A 12-Year Experience
Authors: Sathesh-Kumar T , Rollins Hazel , Cheslyn-Curtis Sarah 
Published: July 2009

INTRODUCTION A small, but significant, number of children require long-term nutritional support. The aim of this study was to demonstrate the safety and efficacy of providing a percutaneous endoscopic gastrostomy (PEG) service for children in a district general hospital and to raise awareness of the suitability of the procedure to be performed on paediatric surgery lists in similar hospitals across the UK. PATIENTS AND METHODS A multidisciplinary paediatric nutrition team was established and all children accepted for PEG insertion between 1995 and 2007 were entered onto a database prospectively and are included in this study. PEG tubes were inserted by the standard pull-through technique under general anaesthetic. RESULTS A total of 172 procedures were performed in 76 children. The median age at first tube insertion was 3 years (range, 0.5–18 years). Length of follow-up ranged from 1 month to 12.6 years. Fifty-eight children (76%) had a neurological abnormality, the commonest being cerebral palsy. All but one procedure were performed successfully, of which 63 (37%) were new insertions, 99 change of tube, 4 changed from surgical gastrostomy and 6 from PEG to button gastrostomy. The median hospital stay was 2 days (range, 2–7 days) for new insertions and 1 day for tube changes. There were 10 (6%) early complications within 30 days, the commonest being peritubal infection (6). The 39 late complications included 16 peritubal infection/granulomata, 9 ‘buried bumpers’, 4 worsening of gastro-oesophageal reflux disease, 2 gastrocolic fistulae, 3 gastrocutaneous fistulae and 4 tubal migration. There was no mortality. CONCLUSIONS We have demonstrated that paediatric PEG procedures and continuing management by a supporting team can be successfully and efficiently provided in the district general hospital. It should be possible for the majority of similar hospitals to provide local access and increase the availability of PEG feeding for children.
Distal Revascularisation with Interval Ligation (DRIL): An Experience
Authors: Field M , Blackwell J , Jaipersad A , Wall M , Silva MA , Morgan RH , Pherwani AD 
Published: July 2009

INTRODUCTION The global increase of chronic renal failure has resulted in a growing number of patients on haemodialysis using arteriovenous fistulas (AVFs). By virtue of their very function, AVFs at times shunt blood away from regions distally, resulting in an ischaemic steal syndrome. Distal revascularisation with interval ligation (DRIL) has been described as a procedure to treat symptomatic ischaemic steal. We present our experience in the management of this complication. PATIENTS AND METHODS Six patients with severe ischaemic steal were treated using a DRIL procedure between May 2004 and June 2007. There were three males and three females, all with elbow brachiocephalic AVFs. Symptoms ranged from severe rest pain to digital gangrene. Published results from international studies of 135 DRIL procedures were also reviewed. RESULTS Vascular access was maintained along with the elimination of ischaemic symptoms in the six patients using an ipsilateral reversed basilic vein graft. Interval ligation of the distal brachial artery was performed at the same time. All patients showed immediate and sustained clinical improvement of symptoms with a demonstrable increase in digital pulse oximetry. CONCLUSIONS DRIL is a beneficial treatment option that has proven successful at alleviating ischemic steal symptoms and preserving vascular access. This avoids placement of central lines, its associated risks, and the need to create an alternative sited fistula.
The EndoAssist™ Robotic Camera Holder as an Aid to the Introduction of Laparoscopic Colorectal Surgery
Authors: Gilbert JM 
Published: July 2009

INTRODUCTION Introducing laparoscopic colorectal surgery is a challenge to the whole surgical team. It is usual for an assistant to hold the laparoscope and be responsible for the surgeon's view of the operative field and a lack of expertise in the assistant can add significant difficulties. The EndoAssist™ is a robotic device that replaces the human assistant and ensures steady visualisation of the operative field and a view which can be controlled by the surgeon. This study describes its use in the introduction of laparoscopic colorectal surgery to a unit. PATIENTS AND METHODS The EndoAssist was employed for the introduction of laparoscopic colorectal surgery in a unit with previous experience of this device for laparoscopic cholecystectomy. It was used in a consecutive series of 77 laparoscopic colectomy operations. RESULTS The robotic device proved successful in the whole range of colorectal operations and a reliable assistant. No problems specific to the device were encountered. CONCLUSIONS The EndoAssist robot is a useful laparoscopic assistant and aided in the introduction of laparoscopic colorectal surgery.
A Prospective Audit of Endoscopic Vein Harvesting for Coronary Artery Bypass Surgery
Authors: Waqar-Uddin Zakariya , Purohit Manoj , Blakeman Nadene , Zacharias Joseph 
Published: July 2009

INTRODUCTION The objectives of this study were to: (i) assess the feasibility of minimally invasive endoscopic harvesting of the long saphenous vein or radial artery for use as conduit during coronary artery bypass surgery in the NHS setting; and (ii) investigate the results of endoscopic vein harvesting with regards to postoperative complications, ability to mobilise, and patient satisfaction. PATIENTS AND METHODS In this prospective audit, 25 consecutive patients, aged 52–90 years, undergoing either coronary artery bypass grafting alone or together with valve surgery or atrial fibrillation ablation were studied. All data were entered in purpose-designed proforma. Pre-operative risk factors including increasing age, diabetes, peripheral vascular disease, obesity, renal impairment, tobacco consumption and steroid use were documented. Time taken for harvest and conversion to traditional open vein harvest, quality of harvested vein in terms of number of repairs and vein damage were recorded. Postoperatively, we recorded harvest site wound complications, number of days to mobilise and total hospital stay. Pain score and patient satisfaction were also assessed. RESULTS There was one death due to myocardial infarction; another patient had postoperative cerebrovascular accident. A total of 43 lengths of grafts were harvested, 41 were long saphenous vein and two radial artery. Vein harvest time reduced significantly from a maximum of 94 min to 34 min for two lengths of long saphenous vein. Three patients required conversion from endoscopic vein harvesting to open vein harvest. The only postoperative complication directly related to endoscopic harvesting was bruising along the tunnel created by the passage of the instruments. None of the patients had any wound complication; none required antibiotics or wound debridement. Mean time to mobilise was 3.4 days. All patients who underwent successful endoscopic vein harvesting expressed satisfaction with regards to postoperative pain and cosmetic result. CONCLUSIONS Competence and ability to harvest conduit in an acceptable time frame are obtainable after a relatively low number of cases. The procedure is associated with a low number of postoperative complications and very high patient satisfaction.
Correlation between Rotator Cuff Tears and Repeated Subacromial Steroid Injections: A Case-Controlled Study
Authors: Bhatia M , Singh B , Nicolaou N , Ravikumar KJ 
Published: July 2009

INTRODUCTION Concern exists regarding potential damage to the rotator cuff from repeated corticosteroid injections into the subacromial space. PATIENTS AND METHODS In this retrospective, case-controlled study, 230 consecutive patients presenting to three orthopaedic units with subacromial impingement and investigated as an end-point with magnetic resonance imaging (MRI) of the shoulder were divided into groups having received less than three or three or more subacromial injections of corticosteroids. RESULTS With no significant difference in age and sex distribution, analysis by MRI showed no significant difference between the two groups in the incidence of rotator cuff tear (P < 1.0). CONCLUSIONS This suggests that corticosteroid use in patients with subacromial impingement should not be considered a causative factor in rotator cuff tears.
Feeding Patients Following Pancreaticoduodenectomy: A UK National Survey
Authors: Phillips Mary , Lordan Jeffrey T , Menezes Neville , Karanjia Nariman D 
Published: July 2009

INTRODUCTION Providing nutrition for patients following pancreaticoduodenectomy (PD) is vital but can be challenging. Due to the lack of UK national guidelines for the provision of nutrition and nutritional pre-operative assessment regarding PD, a national survey was conducted. PATIENTS AND METHODS A questionnaire was sent to the Department of Nutrition and Dietetics at each of the 31 specialist pancreatic centres listed with the Pancreatic Society of Great Britain and Ireland. Questions were asked regarding the nutritional assessment and treatment of patients undergoing classical PD and pylorus-preserving PD (PPPD) resections. RESULTS Twenty-two centres responded to the questionnaire. With regard to PD and PPPD, 82% routinely feed patients following resection, 32% have a regimen for staring feeds, 18% carry out pre-operative nutritional assessment, five centres have funding for an hepatobiliary dietition, and only four centres have a specialist hepatobiliary dietition employed. There was no consensus regarding the type or route of feeding, and at least one centre reported using parenteral nutrition exclusively. CONCLUSIONS Very few centres in the UK have funding for a hepatobiliary dietition. Hence pre-operative nutritional assessment in patients undergoing PD and PPPD does not receive much input. Although the importance of postoperative feeding in these patients is appreciated in all major units, there is no consensus with regards to feeding regimens. The authors hope this observational study will address these issues with this important message and stimulate further study in this area.
Ultrasensitive Prostate Specific Antigen Assay Following Laparoscopic Radical Prostatectomy – An Outcome Measure for Defining the Learning Curve
Authors: Viney R , Gommersall L , Zeif J , Hayne D , Shah ZH , Doherty A 
Published: July 2009

INTRODUCTION Radical retropubic prostatectomy (RRP) performed laparoscopically is a popular treatment with curative intent for organ-confined prostate cancer. After surgery, prostate specific antigen (PSA) levels drop to low levels which can be measured with ultrasensitive assays. This has been described in the literature for open RRP but not for laparoscopic RRP. This paper describes PSA changes in the first 300 consecutive patients undergoing non-robotic laparoscopic RRP by a single surgeon. OBJECTIVES To use ultrasensitive PSA (uPSA) assays to measure a PSA nadir in patients having laparoscopic radical prostatectomy below levels recorded by standard assays. The aim was to use uPSA nadir at 3 months' post-prostatectomy as an early surrogate end-point of oncological outcome. In so doing, laparoscopic oncological outcomes could then be compared with published results from other open radical prostatectomy series with similar end-points. Furthermore, this end-point could be used in the assessment of the surgeon's learning curve. PATIENTS AND METHODS Prospective, comprehensive, demographic, clinical, biochemical and operative data were collected from all patients undergoing non-robotic laparoscopic RRP. We present data from the first 300 consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was measured every 3 months post surgery. RESULTS Median follow-up was 29 months (minimum 3 months). The likelihood of reaching a uPSA of ≤ 0.01 ng/ml at 3 months is 73% for the first 100 patients. This is statistically lower when compared with 83% (P < 0.05) for the second 100 patients and 80% for the third 100 patients (P < 0.05). Overall, 84% of patients with pT2 disease and 66% patients with pT3 disease had a uPSA of ≤ 0.01 ng/ml at 3 months. Pre-operative PSA, PSA density and Gleason score were not correlated with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months. Positive margins correlate with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months but operative time and tumour volume do not (P < 0.05). Attempt at nerve sparing had no adverse effect on achieving a uPSA of ≤ 0.01 ng/ml at 3 months. CONCLUSIONS uPSA can be used as an early end-point in the analysis of oncological outcomes after radical prostatectomy. It is one of many measures that can be used in calculating a surgeon's learning curve for laparoscopic radical prostatectomy and in bench-marking performance. With experience, a surgeon can achieve in excess of an 80% chance of obtaining a uPSA nadir of ≤ 0.01 ng/ml at 3 months after laparoscopic RRP for a British population. This is equivalent to most published open series.
Surgical Management of Boerhaave's Syndrome in a Tertiary Oesophagogastric Centre
Authors: Sutcliffe Robert P , Forshaw Matthew J , Datta Gourab , Rohatgi Ashish , Strauss Dirk C , Mason Robert C , Botha Abraham J 
Published: July 2009

INTRODUCTION The aim of this study was to review the management and outcome of patients with Boerhaave's syndrome in a specialist centre between 2000–2007. PATIENTS AND METHODS Patients were grouped according to time from symptoms to referral (early, < 24 h; late, > 24 h). The effects of referral time and management on outcomes (oesophageal leak, reoperation and mortality) were evaluated. RESULTS Of 21 patients (early 10; late 11), three were unfit for surgery. Of the remaining 18, immediate surgery was performed in 8/8 referred early and 6/10 referred late. Four patients referred late were treated conservatively. Oesophageal leak (78% versus 12.5%; P < 0.05) and mortality (40% versus 0%; P < 0.05) rates were higher in patients referred late. For patients referred late, mortality was higher in patients managed conservatively (75% versus 17%; not significant). CONCLUSIONS The best outcomes in Boerhaave's syndrome are associated with early referral and surgical management in a specialist centre. Surgery appears to be superior to conservative treatment for patients referred late.
Pharmacogenomics of Tamoxifen Therapy
Authors: Brauch Hiltrud , Mürdter Thomas E , Eichelbaum Michel , Schwab Matthias 
Published: July 2009

AbstractBackground: Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor–positive breast cancer.Content: Tamoxifen requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the parent drug, both metabolites have an approximately 100-fold greater affinity for the estrogen receptor and the ability to inhibit cell proliferation. The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. In particular, nonfunctional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 alleles are associated with higher recurrence rates.Summary: Accordingly, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) genotyping before treatment to predict metabolizer status may open new avenues for individualizing endocrine treatment, with the maximum benefit being expected for extensive metabolizers. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used to treat hot flashes, should be avoided because they severely impair formation of the active metabolites.
Method for the Selective Measurement of Amino-Terminal Variants of Procalcitonin
Authors: Struck Joachim , Strebelow Martina , Tietz Sonja , Alonso Christine , Morgenthaler Nils G , van der Hoeven Johannes G , Pickkers Peter , Bergmann Andreas 
Published: July 2009

Abstract
Background: Procalcitonin (PCT) is an established marker for diagnosing and monitoring bacterial infections. Full-length PCT [116 amino acids that make up procalcitonin (PCT1–116)] can be truncated, leading to des-Ala-Pro-PCT (des-Alanin-Prolin-Procalcitonin; PCT3–116). Current immunoassays for PCT (“total PCT”) use antibodies directed against internal epitopes and are unable to distinguish amino-terminal PCT variants. Here we describe the development of monoclonal antibodies recognizing the amino-termini of PCT1–116 and PCT3–116 and their use in the selective measurement of these PCT species.
Methods: With newly developed monoclonal antibodies against the amino-termini of PCT1–116 and PCT3–116, and an antibody against the katacalcin moiety of PCT, we developed and characterized immunoluminometric assays for the 2 PCT peptides. We comparatively assessed the kinetics of PCT variants in a human endotoxemia model.
Results: Monoclonal antibodies against the amino-termini of PCT1–116 and PCT3–116 showed &lt;1% cross-reactivity with other PCT-related peptides. The sandwich assays for PCT1–116 and PCT3–116 had functional assay sensitivities of 5 and 1.2 pmol/L, respectively, and exhibited recoveries within 20% of expected values. Plasma PCT1–116 was stable for 6 h at 22 °C and 24 h at 4 °C, and PCT3–116 was stable for at least 24 h at both temperatures. During experimental endotoxemia in healthy people, both PCT1–116 and PCT3–116 increased early in parallel with total PCT, but further increases in PCT1–116 were significantly slower than for PCT3–116 (P = 0.0049) and total PCT (P = 0.0024).
Conclusions: The new assays selectively measure PCT1–116 and PCT3–116. Both PCT species increase early during endotoxemia but differ in their kinetics thereafter. The selective measurement of PCT species with different in vivo kinetics may be useful in improving PCT-guided therapies.
A Commutable Cytomegalovirus Calibrator Is Required to Improve the Agreement of Viral Load Values between Laboratories
Authors: Caliendo Angela M , Shahbazian Mona D , Schaper Carl , Ingersoll Jessica , Abdul-Ali Deborah , Boonyaratanakornkit Jerry , Pang Xiao-Li , Fox Julie , Preiksaitis Jutta , Schönbrunner E Ralf 
Published: July 2009

Abstract
Background: Viral load testing for cytomegalovirus (CMV) is an important diagnostic tool for the management of transplant recipients and immunocompromised individuals; however, inconsistency among laboratories in quantitative measurements of viral load limits interinstitutional comparisons. These inconsistencies stem from the lack of assays cleared by the US Food and Drug Administration, the absence of international standards, the wide variety of CMV-extraction and -detection methods, and differences in materials used for calibration. A critical component of standardization is the use of calibrators that are traceable and commutable.
Methods: Bland–Altman plots and prediction ellipses were used to test the commutability of 2 CMV calibrators for 2 different quantification methods.
Results: Tests with 2 methods showed 1 calibrator to be commutable and the other to be noncommutable. The results for the commutable calibrator were within the 95% prediction interval of the clinical samples in the Bland–Altman plot and within the 95% prediction ellipse for a simulated commutable calibrator, whereas the results for the noncommutable calibrator were not within these prediction intervals. When used to calibrate patient results, only the commutable calibrator, the OptiQuant® CMVtc Calibration Panel, significantly improved the comparability of viral loads for the 2 different measurement methods.
Conclusions: This study demonstrates that an important goal in the effort to improve healthcare for patients with CMV-related disease is the establishment of traceable and commutable reference materials, including both calibrators and controls. .
Circulating Concentrations of Follistatin-Like 1 in Healthy Individuals and Patients with Acute Coronary Syndrome as Assessed by an Immunoluminometric Sandwich Assay
Authors: Widera Christian , Horn-Wichmann Rüdiger , Kempf Tibor , Bethmann Kerstin , Fiedler Beate , Sharma Sarita , Lichtinghagen Ralf , Leitolf Holger , Ivandic Boris , Katus Hugo A , Giannitsis Evangelos , Wollert Kai C 
Published: July 2009

Abstract
Background: Follistatin-like 1 (FSTL1) is a 308–amino acid secreted glycoprotein. Tissue levels of FSTL1 are induced in animal models and patients with chronic inflammatory and cardiovascular disease. We hypothesized that FSTL1 can be measured in the human circulation and used as a biomarker in acute coronary syndrome (ACS).
Methods: We developed an immunoluminometric assay (ILMA), assessed the preanalytic characteristics of FSTL1, and determined circulating FSTL1 concentrations in 120 apparently healthy individuals and 216 patients with ACS.
Results: The assay had a limit of detection of 0.17 μg/L, limit of quantification of 1.02 μg/L, intraassay imprecision of ≤12.7%, and interassay imprecision of ≤15.4%. Selectivity was demonstrated with size-exclusion chromatography and lack of cross-reactivity with related proteins. The assay was not appreciably influenced by unrelated biological substances. FSTL1 in serum or whole blood was stable at room temperature for 48 h and was resistant to 4 freeze-thaw cycles. Measured FSTL1 concentrations in citrated plasma and heparin-treated plasma were 18% and 17% lower, respectively, than concentrations measured in serum. Apparently healthy individuals presented with a median FSTL1 serum concentration of 7.18 (range 1.06–18.49) μg/L. Serum FSTL1 concentrations were increased in ACS and related to the risk of all-cause mortality during follow-up.
Conclusions: The ILMA permits detection of FSTL1 in human serum and plasma. We expect that the favorable preanalytic characteristics of FSTL1 and the reference limits defined here for apparently healthy individuals will facilitate future studies of FSTL1 as a biomarker in various disease settings, including ACS.