Mentorship in surgical training: current status and a needs assessment for future mentoring programs in surgery.

AIMS: Mentoring has been used extensively in the business world to enhance performance and maximise potential. Despite this, there is currently a paucity of literature describing mentoring for surgical trainees. This study examined the current extent of mentoring and investigated future needs to support this. METHODS: An electronic, 47-item, self-administered questionnaire survey was distributed via national and regional surgical mailing lists and websites through the Association of Surgeons in Training and Specialty Associations in the UK and Republic of Ireland. RESULTS: Overall, 565 fully completed responses were received from trainees in all specialties, grades and training regions. A total of 48.7 % of respondents reported that they have a surgical mentor, with no significant gender difference (p = 0.65). Of respondents, 52.5 % considered their educational supervisor and 45.5 % their current consultant as mentors. Modal duration of mentoring relationships was 1-2 years (24.4 %). A total of 90.2 % of mentors were in the same specialty, 60.7 % in the same hospital, and 88.7 % in the same training region. Mentors covered clinical and professional matters (99.3 %) versus pastoral and non-clinical matters (41.1 %). Mentoring was commonly face to face or via email and not documented (64.7 %). Of the 51.3 % without a mentor, 89.7 % would like a clinical mentor and 51.0 % a pastoral mentor (p < 0.001). Priority mentoring areas included career progression (94.9 %), research (75.2 %), clinical skills (66.9 %) and clinical confidence (58.4 %). A total of 94.3 % would be willing to act as a peer mentor. Only 8.7 % had received mentoring training; 83 % wish to undertake this. CONCLUSIONS: Less than half of surgical trainees identified a mentor. The majority want mentoring on professional topics during their training and would additionally be willing to peer-mentor colleagues, although few have received training for this. Despite an identified need, there is currently no structure for organising this and little national provision for mentoring.

The CKD-DETECT V2.0 study: A randomised controlled trial evaluating the effectiveness of an infographic poster compared with an e-learning program on general practice nurses' knowledge and learning efficiency about chronic kidney disease risk factors and best practice screening procedures.

AIMS AND OBJECTIVES: To evaluate: (a) the effectiveness of an infographic poster compared with an e-learning program on general practice nurses' knowledge about chronic kidney disease risk factors and best practice screening procedures and (b) the effectiveness of an infographic poster compared with an e-learning program on general practice nurses' learning time and learning efficiency. BACKGROUND: The screening and early detection of chronic kidney disease is essential in reducing its burden on the health system and those affected by it. General practice nurses are well-positioned to assist in its early detection. DESIGN: Parallel-group, single-blinded, pre-post interventional randomised control design. METHOD: This study was reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT). Participants were registered or enrolled nurses working in general practice settings across Australia. The intervention group (n = 173) received an infographic poster about chronic kidney disease risk factors and best practice screening procedures, whereas the control group (n = 170) received an interactive e-learning program. Data were collected using an 8-item pre-post knowledge evaluation instrument. Time spent learning were collected through a self-reported log and a login/logout method. RESULTS: The overall intervention effect demonstrated no statistical significance in knowledge scores from the baseline scores between the intervention and control group. The intervention group demonstrated higher learning efficiency in comparison to the control group. CONCLUSION: The study demonstrated an infographic poster is as effective as an e-learning program on improving knowledge scores. However, in comparison to an e-learning program, an infographic poster is a more efficient way of learning. RELEVANCE TO CLINICAL PRACTICE: Infographic posters can be an efficient educational modality to enhance healthcare professionals' knowledge and could be used as public health campaigns in clinical settings to educate the community.

The effect of ergometer design on rowing stroke mechanics.

The effect of rowing ergometer design upon power delivery and coordination patterns of the rowing stroke was analyzed for 14 elite rowers. Rowers were tested in three ergometer conditions: the fixed stretcher Concept2c ergometer, the Concept2c ergometer mounted on sliding rails, and the sliding stretcher RowPerfect ergometer. Ergometers were instrumented to measure the external force generated at the handle and the foot stretcher and a nine-segment inverse dynamics model used to calculate joint and overall power delivery. Peak power generation and absorption at the knee joint was significantly greater, and total power delivered to the ergometer delayed on the fixed stretcher ergometer when compared to the sliding stretcher ergometers. No differences were found in the mechanical energy delivered to the handle of the three ergometers; however, greater joint mechanical energy production of the lower limb reduced mechanical efficiency when rowing the Concept2c fixed ergometer. The fixed foot stretcher on the Concept2c fixed ergometer acts to increase the inertial forces that the rower must overcome at the catch, increasing the moment and power output at the knee, and affecting the coordination pattern during the recovery phase.

The pathology of breast cancer in Jamaica: the National Public Health Laboratory study.

OBJECTIVE: To document the pathologic features of breast cancer in Jamaica. METHODS: The pathology reports and slides of all patients diagnosed with breast cancer at the National Public Health Laboratory between January 1999 and December 2002 were reviewed. Patient age and gender side involved, number of tumours identified, tumour size, histologic type, histologic grade, degree of lymph node involvement and parish of origin of the specimens were documented. RESULTS: There were 772 patients, 762 females and 10 males; age range 21 to 96 (mean 57.9 +/- 15.9) years. There were 778 specimens (6 bilateral cases), the majority of whom originated from Kingston and St Andrew (34.7%). Manchester (22.9%), St Catherine (13.9%) and St Ann (7.3%) were the next most common sources. The left breast was involved in 50.5% of cases. Gross tumour was identified in 641 (82.4%) specimens, the number of tumours ranging from 1 - 6 (mean 1.1 +/- 0.6). The maximum gross tumour dimension ranged from 0.3 to 15 cm (mean 4.1 +/- 2.7 cm). Infiltrating duct carcinoma was the predominant histologic type (69.3 %); 13.3%, 49.5% and 37.2 % of all infiltrating tumours were well, moderately and poorly differentiated respectively. In-situ lesions (7.1% of tumours) were all of the ductal phenotype. Axillary lymph nodes were submitted in 296 (38.1%) cases; metastatic disease was identified in 224 (75.7%) of these. The total number of nodes submitted ranged from 1 - 34 (mean 10.8 +/- 6.7) with an average of 6.1 (+/- 5.8) being positive for metastases (range 1 - 29). CONCLUSIONS: The pathologic features of breast cancer documented in this series including average tumour size, histologic types and grade and the degree of lymph node involvement are consistent with patient presentation at relatively advanced stages of disease and highlight the urgent need for public health intervention including a national screening programme.

Patient perceptions and understanding of obesity related endometrial cancer.

Obesity is the greatest risk factor for endometrial cancer. There is often a lack of recognition amongst patients about this risk. Evidence for weight-loss in the management of endometrial cancer is emerging. This was questionnaire-based study, that examined opinions and attitudes of patients with endometrial cancer and obesity towards obesity as a risk factor for cancer as well as examining their willingness to engage in weight loss interventions as an alternative treatment to endometrial cancer. This survey was conducted in a gynaeoncology out-patient department in Ireland. A total of 45/50 (90%) of questionnaires were completed. The majority of the patients questioned (86.7%; 39/45) agreed that obesity is a disease. Just over half of the cohort (53.3%; 24/45) believed that obesity can cause cancer. Over one-third, 39.9% (18/45) either disagreed or strongly disagreed that obesity is a risk factor for endometrial cancer while 35.5% (16/45) agreed or strongly agreed. Two-thirds (66.6%; 30/45) knew that the greatest amount of weight could be lost through metabolic surgery. Over three-quarters (82.1%; 37/45) of patients surveyed would be willing to engage in a combination of treatments in order to achieve weight-loss should it be proven to have a role in the management of endometrial cancer. This study demonstrates a need for patient education regarding the strong relationship between obesity and endometrial cancer risk. Patients are willing to consider weight loss interventions if they were proven to be as safe and effective as pelvic surgery in the management of endometrial cancer.

Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone.

BACKGROUND AND PURPOSE: Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off-target effects of torcetrapib. EXPERIMENTAL APPROACH: Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models. KEY RESULTS: Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect of torcetrapib was not diminished in the presence of adrenoceptor, angiotensin II or endothelin receptor antagonists. Torcetrapib did not have a contractile effect on vascular smooth muscle suggesting its effects in vivo are via the release of a secondary mediator. Treatment with torcetrapib was associated with an increase in plasma levels of aldosterone and corticosterone and, in vitro, was shown to release aldosterone from adrenocortical cells. Increased adrenal steroid levels were not observed with anacetrapib. Inhibition of adrenal steroid synthesis did not inhibit the pressor response to torcetrapib whereas adrenalectomy prevented the ability of torcetrapib to increase blood pressure in rats. CONCLUSIONS AND IMPLICATIONS: Torcetrapib evoked an acute increase in blood pressure and an acute increase in plasma adrenal steroids. The acute pressor response to torcetrapib was not mediated by adrenal steroids but was dependent on intact adrenal glands.

Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase.

Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone.

Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5alpha-androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5alpha-androstenone sulfate levels, the accumulation of 5alpha-androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r = -0.57; P < 0.01) with 5alpha-androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be > 82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5alpha-androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5alpha-androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2.8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5alpha-androstenone accumulation in fat.

The prevalence of Barrett's oesophagus in a cohort of 1040 Canadian primary care patients with uninvestigated dyspepsia undergoing prompt endoscopy.

BACKGROUND: The prevalence of Barrett's oesophagus in patients undergoing gastroscopy may be influenced by possible referral bias. AIM: To present the prevalence of Barrett's oesophagus from the the Canadian Adult Dyspepsia Empirical Therapy Prompt Endoscopy study and to explore potential risk factors for its presence. METHODS: Patients had not been on treatment for dyspepsia for 2-4 weeks prior to endoscopy, which was performed within 10 working days of presentation. RESULTS: Barrett's oesophagus was endoscopically suspected in 53 of 1040 cases (5%) and histologically confirmed by the presence of intestinal metaplasia in 25 (2.4%). The prevalence of biopsy-proven Barrett's oesophagus was 4% in patients with dominant reflux-like symptoms. Sixty-four percent with confirmed Barrett's oesophagus had dominant reflux-like symptoms compared with 37% without Barrett's oesophagus. Barrett's oesophagus was more common in patients >50 years of age; 68% of cases were males. The mean duration of symptoms was 10 years, yet 16% had symptoms of <1-year duration. Endoscopic reflux oesophagitis was present in 68% of confirmed Barrett's oesophagus patients. CONCLUSIONS: Barrett's oesophagus is confirmed on biopsy in about half of endoscopically suspected Barrett's oesophagus patients. Barrett's oesophagus is more common in males, in those with dominant reflux-like symptoms, and in patients with a longer symptom history.

Deletion of 6q16-q21 in human lymphoid malignancies: a mapping and deletion analysis.

Two distinct regions of minimal deletion (RMD) have been identified at 6q25-q27 in non-Hodgkin's lymphoma (RMD-1), and at 6q21-q23 in acute lymphoblastic leukemia (ALL; RMD-2) by loss of heterozygosity and fluorescence in situ hybridization studies. In this study, 30 overlapping yeast artificial chromosomes (YACs), 1 expressed sequence tag, and 11 novel YAC ends were identified using bidirectional YAC walks between markers D6S447 (proximal) and D6S246 (distal) in RMD-2. The genes AF6q21, human homologue of the Drosophila tailless (HTLX), CD24 antigen, the Kruppel-like zinc finger BLIMP1, and cyclin C (CCNC), previously mapped to 6q21, were accurately positioned in a telomere-to-centromere orientation. Approximately 3.5 Mb were found to separate the BLIMP1 (adjacent to D6S447) and AF6q21 genes (telomeric to D6S246). Deletions of 6q were investigated in 21 cases of ALL using the newly characterized YAC clones in dual-color fluorescence in situ hybridization studies. A region centromeric to D6S447 (containing marker D6S283) and a region telomeric to marker CHLC.GGAT16CO2 (and containing marker D6S268) were identified as distinct and nonoverlapping regions of deletion in ALL.

Induction of cytochrome P-450 and 5-aminolevulinate synthase activities in cultured rat hepatocytes.

Cytochromes P-450IIB1 and P-450IIB2 were recently shown to be inducible in rat hepatocyte cultures maintained on a reconstituted extracellular tumor matrix (Matrigel) as indicated by increases in P-450IIB1 and -IIB2 mRNAs and immunoreactive proteins (J. Cell. Physiol., 134: 309-323, 1988). Here we show that treatment of cultured rat hepatocytes with phenobarbital and other compounds known to induce P-450IIB1/2 in vivo increased spectral cytochrome P-450, immunoreactive proteins, and benzyloxy- and pentoxy-resorufin dealkylases, activities known to be specific for cytochrome P-450IIB1/2. These increases were observed when cells were cultured on either Matrigel or collagen matrix in Williams E medium. Cytochrome P-450III was also increased by phenobarbital and dexamethasone on either matrix. Propoxycoumarin depropylase activity, which has been proposed as a specific activity catalyzed by cytochrome P-450III, was increased 3-4-fold more by treatment with 3-methylcholanthrene than by phenobarbital or dexamethasone. The activity catalyzed by P-450III could be distinguished from that catalyzed by other P-450 forms using the specific inhibitor triacetyloleandomycin. Benzoyloxyresorufin dealkylase was also increased in these cells by treatment with 2,4,5,2',4',5'-hexachlorobiphenyl, glutethimide, or mephenytoin. Treatment with phenobarbital or 2-allyl-2-isopropylacetamide slightly induced 5-aminolevulinate synthase activity. 5-Aminolevulinate synthase activity was slightly increased in cells treated with phenobarbital or 2-allyl-2-isopropylacetamide. Succinyl acetone also induced 5-aminolevulinate synthase activity and, in combination with either of the other two drugs, synergistically increased the enzyme activity regardless of whether cells were cultured on collagen or Matrigel. These results indicate that with simple and economical enzyme assays for holocytochrome P-450 and 5-aminolevulinate synthase, the rat hepatocyte culture system can be used for studies of the interrelationships between phenobarbital induction of cytochrome P-450 and heme metabolism.

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline induces and inhibits cytochrome P450 from the IA subfamily in chick and rat hepatocytes.

Several heterocyclic amines, found in cooked food, are powerful mutagens in the Ames Salmonella mutagenicity test system. One of these, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is one of the most mutagenic chemicals tested in this assay. In primary cultures of chick and rat hepatocytes, MeIQ, by itself, induced cytochrome P450 from the IA subfamily but was a weak inducer compared to 3-methylcholanthrene. However, in both chick and rat hepatocytes in culture, MeIQ decreased the amount of 3-methylcholanthrene-induced ethoxyresorufin deethylase activity, which is catalyzed by cytochrome P450 IA. The protein moiety of cytochrome P450 IA was decreased at MeIQ concentrations of 2.5 micrograms/ml or greater in chick hepatocytes and 25 micrograms/ml in rat hepatocytes. In hepatic microsomes from methylcholanthrene-treated chicks and rats, MeIQ was a competitive inhibitor of both ethoxyresorufin deethylase activity, a reaction catalyzed mainly by rodent cytochrome P450 IA1, and uroporphyrinogen oxidation, a reaction catalyzed by rodent P450 IA2. In cultured chick hepatocytes, MeIQ also decreased cytochrome P450-mediated oxidation of uroporphyrinogen by intact cells. The ability of MeIQ to inhibit as well as to induce cytochrome P450s of the IA subfamily may be important in assessing the mutagenic and carcinogenic effects of MeIQ in mammals.

The role of the RAS pathway in iAMP21-ALL.

Intrachromosomal amplification of chromosome 21 (iAMP21) identifies a high-risk subtype of acute lymphoblastic leukaemia (ALL), requiring intensive treatment to reduce their relapse risk. Improved understanding of the genomic landscape of iAMP21-ALL will ascertain whether these patients may benefit from targeted therapy. We performed whole-exome sequencing of eight iAMP21-ALL samples. The mutation rate was dramatically disparate between cases (average 24.9, range 5-51) and a large number of novel variants were identified, including frequent mutation of the RAS/MEK/ERK pathway. Targeted sequencing of a larger cohort revealed that 60% (25/42) of diagnostic iAMP21-ALL samples harboured 42 distinct RAS pathway mutations. High sequencing coverage demonstrated heterogeneity in the form of multiple RAS pathway mutations within the same sample and diverse variant allele frequencies (VAFs) (2-52%), similar to other subtypes of ALL. Constitutive RAS pathway activation was observed in iAMP21 samples that harboured mutations in the predominant clone (⩾35% VAF). Viable iAMP21 cells from primary xenografts showed reduced viability in response to the MEK1/2 inhibitor, selumetinib, in vitro. As clonal (⩾35% VAF) mutations were detected in 26% (11/42) of iAMP21-ALL, this evidence of response to RAS pathway inhibitors may offer the possibility to introduce targeted therapy to improve therapeutic efficacy in these high-risk patients.

Academic requirements for Certificate of Completion of Training in surgical training: Consensus recommendations from the Association of Surgeons in Training/National Research Collaborative Consensus Group.

BACKGROUND: Surgical trainees are expected to demonstrate academic achievement in order to obtain their certificate of completion of training (CCT). These standards are set by the Joint Committee on Surgical Training (JCST) and specialty advisory committees (SAC). The standards are not equivalent across all surgical specialties and recognise different achievements as evidence. They do not recognise changes in models of research and focus on outcomes rather than process. The Association of Surgeons in Training (ASiT) and National Research Collaborative (NRC) set out to develop progressive, consistent and flexible evidence set for academic requirements at CCT. METHODS: A modified-Delphi approach was used. An expert group consisting of representatives from the ASiT and the NRC undertook iterative review of a document proposing changes to requirements. This was circulated amongst wider stakeholders. After ten iterations, an open meeting was held to discuss these proposals. Voting on statements was performed using a 5-point Likert Scale. Each statement was voted on twice, with ≥80% of votes in agreement meaning the statement was approved. The results of this vote were used to propose core and optional academic requirements for CCT. RESULTS: Online discussion concluded after ten rounds. At the consensus meeting, statements were voted on by 25 delegates from across surgical specialties and training-grades. The group strongly favoured acquisition of 'Good Clinical Practice' training and research methodology training as CCT requirements. The group agreed that higher degrees, publications in any author position (including collaborative authorship), recruiting patients to a study or multicentre audit and presentation at a national or international meeting could be used as evidence for the purpose of CCT. The group agreed on two essential 'core' requirements (GCP and methodology training) and two of a menu of four 'additional' requirements (publication with any authorship position, presentation, recruitment of patients to a multicentre study and completion of a higher degree), which should be completed in order to attain CCT. CONCLUSION: This approach has engaged stakeholders to produce a progressive set of academic requirements for CCT, which are applicable across surgical specialties. Flexibility in requirements whilst retaining a high standard of evidence is desirable.

Oxidation and reduction of membrane-bound cytochrome c in Hemophilus parainfluenzae. Reaction with oxygen, hydrogen peroxide and nitrate.

Cytochromes of the a-, b-, c- and d-type become reduced when intact cells of Hemophilus parainfluenzae have become anaerobic following respiration with substrates such as formate or succinate, as shown previously (J. Biol. Chem. (1970) 254, 5096-5100). In the presence of formate after depletion of O2, there is an unusual two-step time course of reduction of the membrane-bound cytochrome c. The proportion of the cytochrome c which is reduced during the second stage is oxidizable by either nitrate or H2O2 and is reduced again when the nitrate or H2O2 have been depleted. We conclude that the observed two-stage reduction of cytochrome c results from the presence of an oxidant, probably H2O2, produced by reaction of formate dehydrogenase with O2. This was shown by the effects of cyanide, catalase and O2. In addition, no evidence for the production of the oxidant is seen when succinate is the substrate oxidized. Although measurements of absorption spectra indicated only one species of cytochrome c, kinetic evidence is presented for some separation of the cytochrome c into more than one electron transport pathway.

Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.

PURPOSE: To evaluate the efficacy of three hormonal manipulations in the palliation of chemoresistant ovarian cancer, and to analyze the results in the light of other clinical trials. PATIENTS AND METHODS: Three sequential phase II trials were performed in patients with refractory epithelial ovarian carcinoma, using high-dose megestrol acetate (800 mg/d for 30 days, then 400 mg/d), high-dose tamoxifen (80 mg/d for 30 days, then 40 mg/d), and aminoglutethimide (1 g/d plus tapering doses of hydrocortisone). Results were compared with those described in the world literature from trials of the same or similar agents. RESULTS: No responses were seen among 30 assessable patients treated with megestrol acetate, and most (but not all) similar trials have reported low response rates. Five responses (17%) were seen among 29 patients treated with tamoxifen. Two responses exceeded 5 years in duration. No responses were seen among 15 patients treated with aminoglutethimide. CONCLUSION: Antiestrogen therapy may offer the possibility of useful and, occasionally, long-term palliation of refractory epithelial ovarian carcinoma, with little toxicity. There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial.

Heartburn-dominant, uninvestigated dyspepsia: a comparison of 'PPI-start' and 'H2-RA-start' management strategies in primary care--the CADET-HR Study.

BACKGROUND: There are few data on empiric, stepped therapy for heartburn relief or subsequent relapse in primary care. AIMS: To compare heartburn relief produced by a proton pump inhibitor-start or an H(2)-receptor antagonist-start with step-up therapy, as needed, followed by a treatment-free period to assess relapse. METHODS: Heartburn-dominant uninvestigated dyspepsia patients from 46 primary care centres were randomized to one of two active treatment strategies: omeprazole 20 mg daily (proton pump inhibitor-start) or ranitidine 150 mg bid (H2-receptor antagonist-start) for the first 4-8 weeks, stepping up to omeprazole 40 or 20 mg daily, respectively, for 4-8 weeks for persistent symptoms. Daily diaries documented heartburn relief (score < or = 3/7 on < or = of 7 prior days) and relapse (score > or = 4 on > or = 2 of 7 prior days). RESULTS: For 'proton pump inhibitor-start' (n = 196) vs. 'H2-receptor antagonist-start' (n = 194), respectively, heartburn relief occurred in 55.1% vs. 27.3% (P < 0.001) at 4 weeks and in 88.3% vs. 87.1% at 16 weeks. After therapy, 308 patients were heartburn-free (159 vs. 149); median times to relapse were 8 vs. 9 days and cumulative relapse rates were 78.6% vs. 75.8%, respectively. CONCLUSIONS: An empiric 'proton pump inhibitor-start' strategy relieves heartburn more effectively than an 'H2-receptor antagonist-start' strategy up to 12 weeks but has no effect on subsequent relapse, which is rapid in most patients.

Synthesis of free and sulphoconjugated 16-androstene steroids by the Leydig cells of the mature domestic boar.

This study examined the involvement of sulphoconjugation in the biosynthesis of the 16-androstene steroids in Leydig cells of the mature boar, since the formation of steroid sulphoconjugates can reduce the levels of these steroids that accumulate in fatty tissue. Leydig cells were purified from testes of mature male pigs and incubated with pregnenolone, or various individual 16-androstene steroids for 10 min, 1, 4 and 8h. Sulphoconjugated steroids were recovered by solid-phase extraction followed by solvolysis. Profiles of unconjugated and sulphoconjugated steroids were analysed by HPLC. Steroids present in the sulphoconjugated fractions were purified, derivatised as O-methoxime/trimethylsilyl ethers (MO-TMS), and subsequently identified using gas chromatography-mass spectrometry (GC-MS). The principal metabolite produced from incubations with pregnenolone, androstadienol, androstadienone and 5alpha-androstenone was 3beta-androstenol. 16-Androstene steroids that were sulphoconjugated included 5alpha-androstenone, 3beta-androstenol and 3alpha-androstenol. Approximately 70% of the total amount of each 16-androstene steroid was in its sulphoconjugated form after incubations for 4h or more. The finding that sulphoconjugated 5alpha-androstenone was present in large amounts suggests that this steroid may be converted from a 3-keto to a 3-enol form which is subsequently sulphoconjugated. These findings emphasise the need to consider the impact of sulphoconjugation of the 16-androstene steroids and their role in contributing to boar taint.

Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes.

The hepatic metabolism of the 16-androstene steroids was investigated using isolated porcine hepatocytes. This study demonstrated that the liver is capable of producing both phase I and phase II steroid metabolites from 16-androstene steroid precursors. 16-Androstene metabolites were recovered by solid-phase extraction and identified by gas chromatography-mass spectrometry (GC-MS). When 5alpha-androstenone was provided as a substrate, both 3beta- and 3alpha-androstenol were produced as well as a metabolite that showed evidence of hydroxylation. Incubations with the various 16-androstene steroids produced metabolic profiles which suggested that the major role of the liver is phase II conjugation. Sulfoconjugated 16-androstene steroids included androstadienol, 5alpha-androstenone, 3beta-, 3alpha-androstenol, and possibly the hydroxylated metabolite of 5alpha-androstenone. It was determined that hydroxysteroid sulfotransferase (HST) is the likely candidate for the sulfoconjugation of the 16-androstene steroids within the liver. Despite the capacity of the hepatocytes to sulfoconjugate the 16-androstene steroids, the principle metabolites produced from incubations with 5alpha-androstenone, 3beta-, and 3alpha-androstenol were glucuronide conjugates, accounting for approximately 68% of all phase II metabolism. These findings underline the importance of steroid conjugation and suggest that hepatic metabolism of the 16-androstene steroids may influence the levels of 5alpha-androstenone present in the circulation, and thus, capable of accumulating in fat.

The Association of Surgeons in Training Conference: #ASiT2015 Glasgow.

The Association of Surgeons in Training (ASiT) is a professional body and registered charity working to promote excellence in surgical training for the benefit of junior doctors and patients alike. ASiT is in-dependent of the National Health Service (NHS), Surgical Royal Colleges, and specialty associations and represents trainees in all ten surgical specialties. ASiT was delighted to welcome a number of distinguished guests and speakers to Glasgow for #ASiT2015. The theme of 'The Future of Surgery' delved into challenges surgical training faces, exciting developments into using technology to help patients, a glance at the past with the development of the Glasgow Coma Score and whether mortality truly is the future of measured outcomes. More than £3500 of prizes was awarded by the incoming President, Miss. Rhiannon Harries to the highest scoring papers presented selected from over 1000 abstracts submitted.