Aberrant right posterior sectoral duct injury necessitating liver resection.

Aberrant insertion of the right posterior sectoral duct is a particularly hazardous variation of biliary anatomy which makes it prone to injury during laparoscopic cholecystectomy. Such injuries are challenging to manage, as multiple therapeutic options are available with no clear consensus in the literature for an optimal approach. Options include conservative management, intraoperative ligation of the injured duct, Roux-en-Y reconstruction and segmental liver resection. Most cases in the literature advocate for nonoperative management or hepaticojejunostomy. We present an unusual case of aberrant right posterior sectoral duct injury in which neither of these approaches was viable, necessitating a bi-segmental liver resection.

Non-genetic factors that influence methamphetamine intake in a genetic model of differential methamphetamine consumption.

RATIONALE: Genetic and non-genetic factors influence substance use disorders. Our previous work in genetic mouse models focused on genetic factors that influence methamphetamine (MA) intake. The current research examined several non-genetic factors for their potential influence on this trait. OBJECTIVES: We examined the impact on MA intake of several non-genetic factors, including MA access schedule, prior forced MA exposure, concomitant ethanol (EtOH) access, and gamma-aminobutyric acid type B (GABAB) receptor activation. Selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mice participated in this research. RESULTS: MAHDR, but not MALDR, mice increased MA intake when given intermittent access, compared with continuous access, with a water choice under both schedules. MA intake was not altered by previous exposure to forced MA consumption. Male MAHDR mice given simultaneous access to MA, EtOH, and an EtOH+MA mixture exhibited a strong preference for MA over EtOH and EtOH+MA; MA intake was not affected by EtOH in female MAHDR mice. When independent MAHDR groups were given access to MA, EtOH, or EtOH+MA vs. water in each case, MA intake was reduced in the water vs. EtOH+MA group, compared with the water vs. MA group. The GABAB receptor agonist R(+)-baclofen (BAC) not only reduced MA intake but also reduced water intake and locomotor activity in MAHDR mice. There was a residual effect of BAC, such that MA intake was increased after termination of BAC treatment. CONCLUSIONS: These findings demonstrate that voluntary MA intake in MAHDR mice is influenced by non-genetic factors related to MA access schedule and co-morbid EtOH exposure.

Primary colorectal linitis plastica presenting as rapid acute deterioration: a diagnostic dilemma.

We present a rare case of primary colorectal linitis plastica presenting as an acute admission to hospital with a wide range of systemic symptoms, sudden rapid deterioration and subsequent mortality. A postmortem examination revealed a primary linitis plastica of the colon and rectum with diffuse metastatic disease. To our knowledge, this is the first report of primary colorectal linitis plastica presenting as an acute deterioration as a result of extensive metastatic disease.

A systematic review of outcomes in postoperative pain studies in paediatric and adolescent patients: towards development of a core outcome set.

Systematic reviews of postoperative pain in children have called into question the consistency of outcomes measured by clinical triallists as well as the measurement instruments used for assessment. Core outcome set methodology may be a solution to improve standardisation. This study provides an evidence-based foundation for the development of a core outcome set for paediatric postoperative pain studies. We searched ClinicalTrials.gov to identify relevant postoperative pain studies in children. The search yielded 300 registered trials. The following data were then extracted from each of the trials: phase of trial; study type; study design; sample size; all outcomes; whether the outcome was listed as primary, secondary, or tertiary; the measurement instrument for each reported outcome; the specific metric for each outcome; and the type of clinical procedure. Following screening, 134 studies were included in our study. Pain measurement was the most commonly reported outcome (n = 123), followed by total postoperative analgesic dosage (n = 83) and side-effects (n = 25). Temporal trends indicated that pain assessment and unexpected events increased in use between 2000 and 2016, whereas postoperative analgesia measurement decreased. We found a lack of standardisation among outcomes and measurement instruments in paediatric postoperative pain studies. Development of a core outcome set may improve the quality of future trials and allow for more accurate study-to-study comparisons.

Home medicines reviews in Australian war veterans taking warfarin do not influence international normalised ratio control.

BACKGROUND: The clinical outcomes of warfarin are largely dependent on the international normalised ratio (INR) control achieved, and strategies to improve the time in therapeutic range (TTR) should be identified and widely implemented in practice. AIMS: To investigate the influence of pharmacist-led medication reviews on INR control and observe the quality of INR control in Australian veterans who take warfarin. METHODS: We undertook a retrospective cohort study using administrative claims data for Australian veterans and war-widows identified by the Department of Veterans' Affairs who were regularly dispensed warfarin and invited them to contact the research team. Pathology providers were subsequently contacted to provide INR results. RESULTS: INR data were available for 344 of 818 (42.1%) veterans who consented to participate in the study; 64.4% were male and the median age was 83 years. The overall TTR for the veteran cohort during the study period was 64.0%. There was no difference in the TTR in the 6 months following home medicines review (HMR) compared with the control group (63.0% vs 67.0%, P = 0.27), with the TTR in patients with INR data available in the 6 months prior to, and the 6 months following HMR, remaining high (67.9% vs 69.6% P = 0.63). Approximately, one-third of veterans in this study had a percentage TTR below 60%. CONCLUSIONS: INR was well-controlled in this elderly cohort, comparable to that achieved in recent randomised trials involving warfarin. Pharmacist-led medication reviews were not associated with a change in INR control.

Perinatal Treponema pallidum: evidence based guidelines to reduce mother to child transmission.

Universal antenatal screening for T. pallidum is standard in Irish maternity units. The prevalence of adult syphilis has increased in Ireland. We audited the neonatal management of infants exposed to T. pallidum in utero. A cross sectional retrospective analysis of all pregnancies with confirmed positive serology for T. pallidum from January 2005 to December 2010 was conducted at the National Maternity Hospital, Holles St. Data were analysed using SPSS 14.0. Ethical approval was obtained. There were 55,058 live births during the study period. Fifty-eight women had positive serology and 41 met inclusion criteria. Infant evaluation and follow up was decided by allocation to an evidence based algorithm. Twenty-one infants (51%) were accurately allocated and assessed, 5 (12%) had a partial assessment and the algorithm was incorrectly applied in 15 (36%) of cases. Failure to adhere to evidence based neonatal guidelines is common and undermines efficacy of the screening program.

Compact hohlraum configuration with parallel planar-wire-array x-ray sources at the 1.7-MA Zebra generator.

A compact Z-pinch x-ray hohlraum design with parallel-driven x-ray sources is experimentally demonstrated in a configuration with a central target and tailored shine shields at a 1.7-MA Zebra generator. Driving in parallel two magnetically decoupled compact double-planar-wire Z pinches has demonstrated the generation of synchronized x-ray bursts that correlated well in time with x-ray emission from a central reemission target. Good agreement between simulated and measured hohlraum radiation temperature of the central target is shown. The advantages of compact hohlraum design applications for multi-MA facilities are discussed.

The role of surgery in the management of "body packers".

INTRODUCTION: The concealment of packets of illegal substances within body cavities is a common technique for drug smuggling worldwide. The goal of our study was to analyze the results of conservative treatment of "body packers", indications for surgical intervention, and postoperative morbidity. METHODS: This is a retrospective study of patients admitted to our hospital and diagnosed as body packers. The diagnostic protocol included an abdominal X-ray and urinalysis for toxic substances. Only patients with gastrointestinal symptoms, signs of intoxication, or a positive urinalysis were admitted for observation. Conservative management included bowel rest and serial abdominal radiographs to confirm the passage per rectum of all foreign bodies. Asymptomatic patients were given laxatives in the emergency department (ED) to promote bowel movements and were not admitted to the hospital. RESULTS: A total of 763 body packers were admitted to the hospital, all of whom were initially treated conservatively. Of these patients, 47 (6 %) developed complications: 28 with bowel obstruction, three with bowel perforation, and 16 with substance intoxication. In patients developing complications, urinalysis for toxic substances was negative in 19 (40 %). Sixteen (34 %) patients who developed complications were successfully managed nonoperatively. Three (6 %) other patients died before surgery: two deaths resulted from acute toxicity (one of them with an acute onset and a negative urinalysis) and the third patient died of bowel perforation. Laparotomy was required in 28 (3.5 %) body packers admitted for observation. Enterotomy and/or gastrotomy to remove the packets were the most frequently performed procedures. Postoperative morbidity occurred in 57 % of patients, with wound infection being the most frequent complication. CONCLUSIONS: Conservative management was effective in 94 % of symptomatic patients. A laparotomy was required in only 3.5 % of cases. The mortality rate in this series was low, resulting from either severe cocaine poisoning from ruptured packets or bowel perforation.

Diannexin, an annexin A5 homodimer, binds phosphatidylserine with high affinity and is a potent inhibitor of platelet-mediated events during thrombus formation.

BACKGROUND: Shielding of procoagulant phosphatidylserine (PS) with annexin A5 attenuates thrombosis, but annexin A5 (35.7 kDa) is rapidly cleared from the circulation. In contrast, Diannexin, a 73.1 kDa homodimer of annexin A5, has an extended half-life. OBJECTIVES: To quantify the affinity of Diannexin for PS, examine its interaction with activated platelets and determine its effects on platelet-mediated events during thrombus formation. METHODS: The affinities of Diannexin and annexin A5 for PS-containing lipid bilayers were compared using surface plasmon resonance, and binding to activated platelets was assessed by flow cytometry. Calibrated automated thrombography and thromboelastography were employed to study the effects of Diannexin on thrombin generation and platelet-fibrin clot formation, respectively, whereas intravital videomicroscopy was used to examine its effect on platelet accumulation and activation after laser-induced injury to murine cremaster arterioles, and a tail tip bleeding model was used to explore its effects on hemostasis. RESULTS: Diannexin and annexin A5 bind PS with K(D) values of 0.6 and 5 nm, respectively, and both bind to the same subpopulation of PS-exposing platelets. Diannexin inhibited thrombin generation and platelet-fibrin clot formation in vitro at 10 nm (P<0.05-0.001 compared with control), and reduced platelet accumulation at 1 µg g(-1) (P<0.05) and activation at 0.25 µg g(-1) (P<0.001) in experimentally induced arterial thrombi in mice while increasing blood loss at 1 µg g(-1) (P<0.01). CONCLUSIONS: Diannexin binds to PS with high affinity and is a potent inhibitor of platelet-mediated events during thrombus formation.

The potential for intelligent decision support systems to improve the quality and consistency of medication reviews.

WHAT IS KNOWN AND OBJECTIVE: Drug-related problems (DRPs) are of serious concern worldwide, particularly for the elderly who often take many medications simultaneously. Medication reviews have been demonstrated to improve medication usage, leading to reductions in DRPs and potential savings in healthcare costs. However, medication reviews are not always of a consistently high standard, and there is often room for improvement in the quality of their findings. Our aim was to produce computerized intelligent decision support software that can improve the consistency and quality of medication review reports, by helping to ensure that DRPs relevant to a patient are overlooked less frequently. A system that largely achieved this goal was previously published, but refinements have been made. This paper examines the results of both the earlier and newer systems. METHODS: Two prototype multiple-classification ripple-down rules medication review systems were built, the second being a refinement of the first. Each of the systems was trained incrementally using a human medication review expert. The resultant knowledge bases were analysed and compared, showing factors such as accuracy, time taken to train, and potential errors avoided. RESULTS AND DISCUSSION: The two systems performed well, achieving accuracies of approximately 80% and 90%, after being trained on only a small number of cases (126 and 244 cases, respectively). Through analysis of the available data, it was estimated that without the system intervening, the expert training the first prototype would have missed approximately 36% of potentially relevant DRPs, and the second 43%. However, the system appeared to prevent the majority of these potential expert errors by correctly identifying the DRPs for them, leaving only an estimated 8% error rate for the first expert and 4% for the second. WHAT IS NEW AND CONCLUSION: These intelligent decision support systems have shown a clear potential to substantially improve the quality and consistency of medication reviews, which should in turn translate into improved medication usage if they were implemented into routine use.

A methodological framework for estimating the clinical and economic value of community pharmacists' clinical interventions using expert opinion.

WHAT IS KNOWN AND OBJECTIVE: Studies of the outcomes of clinical interventions (CIs) performed by community pharmacists are limited. The economic models used in most studies of CIs have been simplistic, often failing to fully capture the counterfactual when estimating savings in health resources resulting from CIs. This paper aimed to describe the complexities involved in estimating the clinical and economic outcomes of CIs performed by community pharmacists when using expert opinion and suggest avenues for improvement. METHODS: Existing models were reviewed, from which a range of key parameters required to evaluate the outcomes of CIs were identified. The considerations necessary to generate potentially more robust estimates of these parameters were discussed. RESULTS AND DISCUSSION: CIs performed by community pharmacists may result in a multitude of effects on numerous health services. By utilizing the approaches described in this paper, researchers working in this field should be able to generate improved estimates of health resource savings and quality of life effects resulting from CIs performed by community pharmacists, when compared to previous efforts. WHAT IS NEW AND CONCLUSION: This article offers recommendations designed to improve the robustness of evaluation when using expert opinion to evaluate CIs performed by community pharmacists.

Influence of induced axial magnetic field on plasma dynamics and radiative characteristics of Z pinches.

The influence of an induced axial magnetic field on plasma dynamics and radiative characteristics of Z pinches is investigated. An axial magnetic field was induced in a novel Z-pinch load: a double planar wire array with skewed wires (DPWAsk), which represents a planar wire array in an open magnetic configuration. The induced axial magnetic field suppressed magneto-Rayleigh-Taylor (MRT) instabilities (with m = 0 and m = 1 instability modes) in the Z-pinch plasma. The influence of the initial axial magnetic field on the structure of the plasma column at stagnation was manifested through the formation of a more uniform plasma column compared to a standard double planar wire array (DPWA) load [V. L. Kantsyrev et al., Phys. Plasmas 15, 030704 (2008)]. The DPWAsk load is characterized by suppression of MRT instabilities and by the formation of the sub-keV radiation pulse that occurs before the main x-ray peak. Gradients in plasma parameters along the cathode-anode gap were observed and analyzed for DPWAsk loads made from low atomic number Z (Al) and mid-Z (brass) wires.

Laparoscopic adrenalectomy: Single centre experience.

BACKGROUND: Laparoscopic adrenalectomy is an attractive alternative to the traditional open approach in the surgical excision of an adrenal gland. It has replaced open adrenalectomy in our institution and we review our experience to date. METHODS: All cases of laparoscopic adrenalectomies in our hospital over eight years (from 2001 to May 2009) were retrospectively reviewed. Patient demographics, diagnosis, length of hospital stay, histology and all operative and post-operative details were evaluated. RESULTS: Fifty-five laparoscopic adrenalectomies (LA) were performed on 51 patients over eight years. The mean age was 48 years (Range 16-86 years) with the male: female ratio 1:2. Twenty-three cases had a right adrenalectomy, 24 had a left adrenalectomy and the remaining four patients had bilateral adrenalectomies. 91% were successfully completed laparoscopically with five converted to an open approach. Adenomas (functional and non functional) were the leading indication for LA, followed by phaeochromocytomas. Other indications for LA included Cushing's disease, adrenal malignancies and rarer pathologies. There was one mortality from necrotising pancreatitis following a left adrenalectomy for severe Cushing's disease, with subsequent death 10 days later. CONCLUSION: Laparoscopic adrenalectomy is effective for the treatment of adrenal tumours, fulfilling the criteria for the ideal minimally invasive procedure. It has replaced the traditional open approach in our centre and is a safe and effective alternative. However, in the case of severe Cushing's disease, laparoscopic adrenalectomy has the potential for significant adverse outcomes and mortality.

Inappropriate prescribing in older residents of Australian care homes.

WHAT IS KNOWN AND OBJECTIVE: The incidence of inappropriate prescribing is higher amongst the older age group than the younger population. Inappropriate prescribing potentially leads to drug-related problems such as adverse drug reactions. We aimed to determine the prevalence of inappropriate prescribing in residents of Tasmanian (Australia) residential care homes using Beers and McLeod criteria. METHODS: Patient demographics, medical conditions and medications were collected from medical records. The patients who fulfilled either Beers or McLeod criteria were identified and the characteristics of these patients were then compared. RESULTS: Data for 2345 residents were collected between 2006 and 2007. There were 1027 (43.8%) patients prescribed at least one inappropriate medication. Beers criteria identified more patients (828 patients, 35.3%) as being prescribed inappropriate medication compared with McLeod criteria (438 patients, 18.7%). Patients taking psychotropic medication/s, more than six medications or diagnosed with five or more medical conditions were more likely to be prescribed an inappropriate medication (P<0.001). The most frequently identified inappropriate medications included benzodiazepines, amitriptyline, oxybutynin and non-steroidal anti-inflammatory drugs. WHAT IS NEW AND CONCLUSION: Inappropriate prescribing, as defined by either Beers criteria or McLeod criteria, is relatively common in Australian nursing homes. The prevalence of inappropriate prescribing, and factors influencing it, are consistent with other countries. Both Beers and McLeod criteria are a general guide to prescribing, and do not substitute for professional judgment.

Quantitative magnetic resonance angiography of the cerebrovasculature in physiologic and pathologic states.

BACKGROUND: In the past, clinical decisions regarding treatment of neurovascular disorders leading to ischemia have been guided by the percentage of stenosis of the vessel in question. However, such an approach assumes a predictable and stable relationship between the percentage of stenosis and the degree of flow reduction it causes. Historically, this type of relationship has been difficult to document. Thus, a method for noninvasively measuring the absolute flow of specific cerebral arteries is of potential practical value. METHODS: We set to quantify the mean blood flow (Qm, in mL/min) in the cerebral arteries using quantitative magnetic resonance angiography (QMRA), and to compare the findings in normal vessels with those found in vessels considered pathologically narrowed. Specific vascular segments were identified, studied, and the results entered into a database. Statistical analyses of the measurements were carried out using StatPlus for Microsoft Excel. It involved comparing of the Qm found in specific vessels, as well as those found in normal and abnormal vessels, using analysis of variance (ANOVA). The abnormal vessels were selected from specifically identified magnetic resonance angiography (MRA) studies. RESULTS: A total of 57 patients, 26 men and 31 women, with ages ranging from 19 to 86 years (mean = 64.5), underwent MRA with subsequent QMRA of 157 arteries. The latter included 72 internal carotid (ICA), 45 vertebral (VA), 18 common carotid (CCA), 13 middle cerebral (MCA), and nine basilar (BA) arteries. The mean Qm obtained were CCA = 313.9 (+/-115.4), ICA = 231.1 (+/-83.7), VA = 90.5 (+/-45.8), MCA = 92.5 (+/-62.3) and BA = 120.1 (+/-64.5). ANOVA showed significant differences between individual vessels (P < .00001). The values obtained were consistent with those predicted mathematically, as derivatives of their proportional contributions to overall cerebral arterial flow (Qbrain) as a product of the normal cardiac output (CO) [ie, Qbrain = CO*.2]. Further ANOVA of the normal and abnormal vessels showed statistically significant differences between the two groups (186.5 +/- 108.6 vs. 117.9 +/- 76.1, respectively; P= .000514). CONCLUSIONS: The use of QMRA provides the mean for direct measurement of absolute blood flow within the cerebral arteries in physiologic and pathologic states. This technique may be of future importance in characterizing absolute flow compromise in the cerebral arteries under a variety of clinically relevant circumstances.

The benefit-to-risk profile of melagatran is superior to that of hirudin in a rabbit arterial thrombosis prevention and bleeding model.

Although hirudin is better than heparin at preventing recurrent ischemia in patients with unstable angina, hirudin produces more bleeding. The purpose of this study was to use a rabbit arterial thrombosis prevention and ear bleeding model to determine whether for equivalent efficacy, melagatran, a synthetic direct thrombin inhibitor, is safer than hirudin. A combination of balloon injury and stasis was used to induce thrombosis in the distal aorta, and patency and blood flow were continuously monitored with ultrasonic flow probes. Rabbits were randomized to melagatran (in total doses of 78-313 nmol kg(-1)), hirudin (in total doses of 18-107 nmol kg(-1)), or saline over 90 min. To assess safety, blood loss from standardized ear incisions was measured. Both melagatran and hirudin produced dose-dependent increases in patency and blood flow. At doses that maintained the highest levels of patency, however, melagatran produced 2-3-fold less bleeding than hirudin. Thus, at maximally effective doses, melagatran causes less bleeding than hirudin in this model. These findings raise the possibility that some direct thrombin inhibitors are safer than others.

Conformational changes in thrombin when complexed by serpins.

Thrombin possesses two positively charged surface domains, termed exosites, that orient substrates and inhibitors for reaction with the enzyme. Because the exosites also allosterically modulate thrombin's activity, we set out to determine whether the structure or function of the exosites changes when thrombin forms complexes with antithrombin, heparin cofactor II, or alpha(1)-antitrypsin (M358R), serpins that utilize both, one, or neither of the exosites, respectively. Using a hirudin-derived peptide to probe the integrity of exosite 1, no binding was detected when thrombin was complexed with heparin cofactor II or alpha(1)-antitrypsin (M358R), and the peptide exhibited a 55-fold lower affinity for the thrombin-antithrombin complex than for thrombin. Bound peptide or HD-1, an exosite 1-binding DNA aptamer, was displaced from thrombin by each of the three serpins. Thrombin binding to fibrin also was abrogated when the enzyme was complexed with serpins. These data reveal that, regardless of the initial mode of interaction, the function of exosite 1 is lost when thrombin is complexed by serpins. In contrast, the integrity of exosite 2 is largely retained when thrombin is complexed by serpins, because interaction with heparin or an exosite 2-directed DNA aptamer was only modestly altered. The disorganization of exosite 1 that occurs when thrombin is complexed by serpins is consistent with results of protease sensitivity studies and crystallographic analysis of a homologous enzyme-serpin complex.

Construction of neocentromere-based human minichromosomes by telomere-associated chromosomal truncation.

Neocentromeres (NCs) are fully functional centromeres that arise ectopically in noncentromeric regions lacking alpha-satellite DNA. Using telomere-associated chromosome truncation, we have produced a series of minichromosomes (MiCs) from a mardel(10) marker chromosome containing a previously characterized human NC. These MiCs range in size from approximately 0.7 to 1.8 Mb and contain single-copy intact genomic DNA from the 10q25 region. Two of these NC-based Mi-Cs (NC-MiCs) appear circular whereas one is linear. All demonstrate stability in both structure and mitotic transmission in the absence of drug selection. Presence of a functional NC is shown by binding a host of key centromere-associated proteins. These NC-MiCs provide direct evidence for mitotic segregation function of the NC DNA and represent examples of stable mammalian MiCs lacking centromeric repeats.

Molecular basis for the susceptibility of fibrin-bound thrombin to inactivation by heparin cofactor ii in the presence of dermatan sulfate but not heparin.

Although fibrin-bound thrombin is resistant to inactivation by heparin.antithrombin and heparin.heparin cofactor II complexes, indirect studies in plasma systems suggest that the dermatan sulfate.heparin cofactor II complex can inhibit fibrin-bound thrombin. Herein we demonstrate that fibrin monomer produces a 240-fold decrease in the heparin-catalyzed rate of thrombin inhibition by heparin cofactor II but reduces the dermatan sulfate-catalyzed rate only 3-fold. The protection of fibrin-bound thrombin from inhibition by heparin.heparin cofactor II reflects heparin-mediated bridging of thrombin to fibrin that results in the formation of a ternary heparin.thrombin.fibrin complex. This complex, formed as a result of three binary interactions (thrombin.fibrin, thrombin.heparin, and heparin.fibrin), limits accessibility of heparin-catalyzed inhibitors to thrombin and induces conformational changes at the active site of the enzyme. In contrast, dermatan sulfate binds to thrombin but does not bind to fibrin. Although a ternary dermatan sulfate. thrombin.fibrin complex forms, without dermatan sulfate-mediated bridging of thrombin to fibrin, only two binary interactions exist (thrombin.fibrin and thrombin. dermatan sulfate). Consequently, thrombin remains susceptible to inactivation by heparin cofactor II. This study explains why fibrin-bound thrombin is susceptible to inactivation by heparin cofactor II in the presence of dermatan sulfate but not heparin.