The role of glucagon in weight loss-mediated metabolic improvement: a systematic review and meta-analysis.

Aims This meta-analysis aimed to investigate the role of glucagon suppression in regulating glucose homeostasis following diet or bariatric surgery. Methods A comprehensive search of intervention and observational studies was conducted in Medline, Scopus, Web of Science, PubMed and Embase. Random effects model meta-analysis was performed. Primary outcomes were (i) body weight change, (ii) fasting glucagon, (iii) fasting glucose and (iv) fasting insulin concentrations. Results Twenty articles reporting data from 29 interventions were eligible for analysis. Bariatric surgery caused greater weight loss than diet (bariatric -29.7 kg [CI:-36.8, -22.6]; diet -5.8 kg [CI: -8.4, -3.3]; P < 0.00001), an effect that remained significant after adjusting for study duration (P < 0.05). Mean fasting glucagon decreased in parallel with weight loss (-11.8 ng/L [CI: -15.9, -7.8]; P < 0.00001) with no difference between bariatric and diet intervention. Both fasting glucose, and insulin decreased following weight loss (both P < 0.00001; glucose -1.7 mmol/L [CI: -2.0, -1.3]; insulin -50.6 pmol/L [CI: -66.5, -34.7] with greater decrease in fasting insulin between bariatric versus diet (P = 0.01). Conclusions Synergistic suppression of fasting glucagon and insulin resistance may act together to restore normoglycaemia following weight loss. Whether suppression of plasma glucagon may contribute to increased hunger after weight loss and gradual weight regain is not yet known.

The use of alpha 2 agonists during idiopathic scoliosis repair : a narrative review of the literature.

Alpha 2 agonists are appreciated drugs designed for the peri-operative period, because of their anxiolytic, sedative and analgesic properties. However, they are usually avoided during scoliosis surgery, a longlasting major procedure involving healthy patients, because of their potential effects on Somatosensory and Motorevoked potentials. The absence ofrecommendations suggests that their effects on evoked potentials are still unclear. Thus, we tried in this narrative review to identify the literature representative of the effects of clonidine and dexmedetomidine on evoked potentials, on human beings, published between 1988 and 2015 in English or French, using GOOGLE SCHOLAR and PUBMED. Paucity of literature prevented any conclusion about Clonidine's effects on evoked potentials, but no data suggested a noxious effect of Clonidine on evoked potentials, used in oral premedication (300 µg) or during the procedure (2 to 5 µg/kg). If literature was more extensive for dexmedetomidine, studies were still controversial. Although the majority of the studies did not find statistically significant differences concerning the effects of this drug on evoked potentials (loading dose of 0.3 to 1 µg/ kg followed by continuous infusion of 0.3 to 0.8 µg/kg/h), 2 case reports and 2 studies described substantial decreases. However, dexmedetomidine's shorter duration of action allowed a quick return to basal situation within an hour. In conclusion, more studies are needed in order to evaluate the effects of alpha 2 agonists on evoked potentials and to assess the safety of their use in this setting.

Biosensor Regeneration: A Review of Common Techniques and Outcomes.

Biosensors are ideally portable, low-cost tools for the rapid detection of pathogens, proteins, and other analytes. The global biosensor market is currently worth over 10 billion dollars annually and is a burgeoning field of interdisciplinary research that is hailed as a potential revolution in consumer, healthcare, and industrial testing. A key barrier to the widespread adoption of biosensors, however, is their cost. Although many systems have been validated in the laboratory setting and biosensors for a range of analytes are proven at the concept level, many have yet to make a strong commercial case for their acceptance. Though it is true with the development of cheaper electrodes, circuits, and components that there is a downward pressure on costs, there is also an emerging trend toward the development of multianalyte biosensors that is pushing in the other direction. One way to reduce the cost that is suitable for certain systems is to enable their reuse, thus reducing the cost per test. Regenerating biosensors is a technique that can often be used in conjunction with existing systems in order to reduce costs and accelerate the commercialization process. This article discusses the merits and drawbacks of regeneration schemes that have been proven in various biosensor systems and indicates parameters for successful regeneration based on a systematic review of the literature. It also outlines some of the difficulties encountered when considering the role of regeneration at the point of use. A brief meta-analysis has been included in this review to develop a working definition for biosensor regeneration, and using this analysis only ∼60% of the reported studies analyzed were deemed a success. This highlights the variation within the field and the need to normalize regeneration as a standard process across the field by establishing a consensus term.

Complications of continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) is used to treat end-stage renal failure in an increasing number of patients. CAPD has an advantage over hemodialysis in that it allows patients greater freedom to perform daily activities; it also provides other clinical benefits. However, the long-term effectiveness of CAPD is limited by complications, which have various causes. Complications with an infectious cause include bacterial peritonitis, tuberculous peritonitis, and infections of the catheter exit site and tunnel. Noninfectious complications include catheter dysfunction, dialysate leakage, hernias, and sclerosing encapsulating peritonitis. Many imaging modalities-radiography, ultrasonography, peritoneal scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging-are useful for characterizing these complications. CT peritoneography and MR peritoneography are techniques specifically suited to this purpose. Imaging plays a critical role in ensuring that complications are detected early and managed appropriately.

Mirizzi syndrome associated with hepatic artery pseudoaneurysm: a case report.

INTRODUCTION: This is the first case report of Mirizzi syndrome associated with hepatic artery pseudoaneurysm. CASE PRESENTATION: A 54-year-old man presented with painful obstructive jaundice and weight loss. Computed tomography showed a hilar mass in the liver. Following an episode of haemobilia, angiography demonstrated a pseudoaneurysm of a branch of the right hepatic artery that was embolised. At surgery, a gallstone causing Mirizzi type II syndrome was found to be responsible for the biliary obstruction and a necrotic inflammatory mass and haematoma were found to be extending into the liver. The mass was debrided and drained, the obstructing stones removed and the bile duct drained with a t-tube. The patient made a full recovery. CONCLUSION: This case highlights another situation where there may be difficulty in differentiating Mirizzi syndrome from biliary tract cancer.

Telephone triage, expert systems and clinical expertise.

This paper reports on a qualitative study of the use of an expert system developed for the British telephone triage service NHS Direct. This system, known as CAS, is designed to standardise and control the interaction between NHS Direct nurses and callers. The paper shows, however, that in practice the nurses use CAS in a range of ways and, in so doing, privilege their own expertise and deliver an individualised service. The paper concludes by arguing that NHS Direct management's policy of using CAS as a means of standardising service delivery will achieve only limited success due not only to the professional ideology of nursing but also to the fact that rule-based expert systems capture only part of what 'experts' do.

Embolisation of cancer: what is the evidence?

Embolisation has become an accepted modality of cancer treatment in patients with a variety of clinical scenarios. It is commonly used in clinical practice in the treatment of hepatocellular carcinoma, hepatic metastases from colorectal cancer and neuroendocrine tumours, and renal cell carcinoma. This review summarizes the current evidence for the efficacy of embolotherapy in these clinical settings, together with the associated complications.

Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.

In humans, ten Toll-like receptor (TLR) paralogues sense molecular components of microbes, initiating the production of cytokine mediators that create the inflammatory response. Using N-ethyl-N-nitrosourea, we induced a germline mutation called Lps2, which abolishes cytokine responses to double-stranded RNA and severely impairs responses to the endotoxin lipopolysaccharide (LPS), indicating that TLR3 and TLR4 might share a specific, proximal transducer. Here we identify the Lps2 mutation: a distal frameshift error in a Toll/interleukin-1 receptor/resistance (TIR) adaptor protein known as Trif or Ticam-1. Trif(Lps2) homozygotes are markedly resistant to the toxic effects of LPS, and are hypersusceptible to mouse cytomegalovirus, failing to produce type I interferons when infected. Compound homozygosity for mutations at Trif and MyD88 (a cytoplasmic TIR-domain-containing adaptor protein) loci ablates all responses to LPS, indicating that only two signalling pathways emanate from the LPS receptor. However, a Trif-independent cell population is detectable when Trif(Lps2) mutant macrophages are stimulated with LPS. This reveals that an alternative MyD88-dependent 'adaptor X' pathway is present in some, but not all, macrophages, and implies afferent immune specialization.

Indomethacin blocks pre-partum nest building behaviour in the pig (Sus scrofa): effects on plasma prostaglandin F metabolite, oxytocin, cortisol and progesterone.

In the pig, nest building occurs in the day preceding parturition (gestation=114--116 days). Nest building behaviour can be induced in pregnant, pseudopregnant and cyclic female pigs following injection of prostaglandin F2alpha. Here we investigated behaviour and endocrine changes after the administration of indomethacin, which inhibits cyclo-oxygenase enzymes and thus prostaglandin synthesis. In experiment 1, pregnant primiparous pigs (gilts) were blood sampled through jugular vein catheters every 20 min from 1000 h on day 113 of pregnancy and behaviour was recorded until birth. Two hours after pre-partum nest building began, animals received 4 mg/kg indomethacin (n=7) or control vehicle (n=8) intramuscularly. Indomethacin-treated animals showed less nest building than controls between 1 and 5 h after injection (P<0.05), during which time they were mostly inactive and lay down for longer than controls. From 5 h before birth until birth there was no significant treatment difference in nest building behaviour. There was a tendency for the start of birth to be delayed in indomethacin-treated animals. Plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (a major metabolite of prostaglandin F2 alpha) rose during pre-injection nest building and then fell following indomethacin treatment, but was not significantly different between groups when behaviour differed. Plasma oxytocin, cortisol and progesterone were not significantly affected by treatment. In experiment 2, indomethacin-treated non-pregnant gilts (n=7) did not show any changes in activity or posture compared with vehicle-treated controls (n=6) between 90 and 150 min after treatment. These results suggested that indomethacin treatment reversibly and specifically inhibits porcine pre-partum nest building by a mechanism that may involve endogenous prostaglandin F2 alpha synthesis inhibition but is independent of circulating oxytocin, cortisol and progesterone concentrations.

Effect of intrathecal fentanyl on oxytocin secretion in pregnant women not in labour.

We studied the effects of spinal intrathecal fentanyl on oxytocin secretion in 20 healthy women prior to an elective caesarean delivery at term under spinal anaesthesia. The women were randomly allocated into two groups with respect to spinal anaesthesia. Group I (n=10) received intrathecal bupivacaine (15 mg) plus fentanyl (25 microgram), and Group II (n=10) received intrathecal bupivacaine (15 mg) alone, prior to caesarean section. The two groups were comparable demographically. Altogether, ten samples of 4.5 ml of blood (taken every 60 s) were obtained before and ten samples were obtained after the intrathecal administration of the drug and establishment of the T6 block, and plasma oxytocin concentrations were assayed for each subject. Oxytocin was measured by RIA. We found no significant differences in plasma oxytocin concentrations of individual subjects before and after intrathecal injection. In addition, there were no significant differences in plasma oxytocin concentrations between the two groups when pooled samples from the subjects were compared for the pre- and post-intrathecal injection phases. We conclude that the spinal intrathecal administration of fentanyl does not suppress oxytocin secretion in pregnant women who are not in labour at term.

Gender-specific issues in the treatment of migraine.

Migraine is approximately three times more common in women than in men. Women tend to have longer attacks and are more likely than men to experience aura with migraine, but both sexes can experience frequent and severe attacks. Treatment principles for migraine and guidelines for the use of prophylactic and abortive therapies are generally consistent between males and females. However, due to hormonal changes induced in the female during menstruation, oral contraceptive use, pregnancy, and menopause, gender-specific therapeutic strategies are often necessary when treating migraine in females.

Undisclosed port-wine stain--anesthetic implications and psychosocial considerations: a case report.

Port-wine stains (nevus flammeus, port-wine nevus) are congenital vascular lesions that have psychological and physiological implications for patient care. The location and size of these lesions can lead to complications related to anesthetic management. Facial lesions have the most profound psychological effect on the patient with respect to behavior alterations and reluctance to disclose the lesion's presence. Covering makeup has become increasingly effective not only in concealing the lesion, but also in being nearly undetectable during routine examination. Issues such as agent choice, surgical position, frequency of positioning evaluation, and choice of intravenous fluid should be considered when caring for a patient with a port-wine stain. In this case study the authors describe the anesthesia implications and outcome in a patient who refused to disclose her port-wine lesion in the preoperative interview and who ignored preoperative instructions to remove all makeup before presenting for surgery.

The role of the coronoid process in elbow stability. A biomechanical analysis of axial loading.

BACKGROUND: The current treatment of coronoid process fractures of the ulna is based on the classification system of Regan and Morrey. We found no biomechanical studies that specifically addressed the role of the coronoid process in elbow stability. In the present investigation, the elbows of cadavera were tested before and after fracture of the coronoid process to assess the stabilizing contribution of the coronoid process under axial loading. METHODS: Six fresh-frozen cadaveric elbows were tested mechanically. All soft tissue surrounding the elbow, including the skin, was left intact. An axial load compressing the elbow joint was applied along the shaft of the forearm in the sagittal plane. A displacement of fifteen millimeters per minute was applied until a load of 100 newtons was attained. Each elbow was tested in 15, 30, 45, 60, 75, 90, 105, and 120 degrees of flexion. Next, less than 25 percent, 25 to 50 percent, or more than 50 percent of the coronoid process was fractured with an osteotome under radiographic guidance, and the testing was repeated. Each elbow served as its own control, and one elbow was used for two tests; therefore, a total of seven situations were investigated. The difference in displacements between the intact and osteotomized elbows was measured. RESULTS: There was no significant difference, at any flexion position, in posterior axial displacement between the intact elbows and the elbows in which 50 percent or less of the coronoid process was fractured (type I and type II) (p = 0.43). There were significant differences, across all flexion positions, in posterior axial displacement between the intact elbows and the elbows in which more than 50 percent of the coronoid process was fractured (type III) (p = 0.006). Specimens with a type-III fracture also showed a significant increase in displacement compared with specimens with a type-I or type-II fracture (p = 0.012). Specifically, from 60 to 105 degrees of flexion, a significant increase in posterior translation of up to 2.4 millimeters was found (p<0.05). CONCLUSIONS: In response to axial load, elbows with a fracture involving more than 50 percent of the coronoid process displace more readily than elbows with a fracture involving 50 percent or less of the coronoid process, especially when the elbow is flexed 60 degrees and beyond.

Building a year-round immunization program.

Each year, an estimated 55,000 to 80,000 people die from vaccine-preventable diseases. More pharmacists are needed to advocate, facilitate, and deliver immunizations throughout the year. Pharmacists who want to develop a year-round immunization program should begin by developing a comprehensive business plan. By implementing a successful year-round immunization program, pharmacists can reduce morbidity and mortality from a range of vaccine-preventable infections.

Behavioral effects of betacarbolines in pigs:. anxiety or aversion?

Betacarbolines are often considered to be anxiogenic and may, therefore, have similar behavioral effects to those of corticotrophin releasing hormone (CRH); however, their actions have been little studied in pigs. This investigation was concerned with the effects of ethyl-beta-carboline-3-carboxylate (BCCE) and noreleagnine (NOR) on operant feeding, cortisol release, and overt behavior in swine, all of which are known to be affected by CRH in this species. Three experiments are described in which BCCE or NOR were given intravenously to prepubertal boars (n = 7). In Experiment 1, 400 microg/kg, but not 100 or 200 microg/kg, BCCE produced a rapid inhibition of ingestive activity whereas NOR (100, 200, or 400 microg/kg) was without effect. In Experiment 2, both BCCE and NOR increased plasma cortisol, but not growth hormone, concentrations. In Experiment 3, a high dose of BCCE (2 mg/kg) produced transient arousal and a sustained increase in respiration rate and plasma cortisol. These results indicate that although the responses of pigs to BCCE and CRH are similar in some respects, there are also marked behavioral differences. The possibility that BCCE has aversive rather than anxiogenic actions in this species is discussed.

Release of oxytocin and prostaglandin f(2alpha) around teasing, natural service and associated events in the mare.

Mating has been shown in many species to provoke the release of oxytocin (OT). In our study, various stimuli were applied to mares to study release of OT and prostaglandin F(2alpha) (PGF(2alpha)) associated with mating. Blood samples were collected from mares around the time of teasing both in oestrus and dioestrus and at mating. For comparison, blood samples were also collected at the time of manual manipulation of the genital tract and after intrauterine infusion of 500 ml phosphate buffered saline (PBS). Additional samples were collected 16 to 18 h after mating. Mating caused a significant increase in OT in all mares and teasing caused a significant OT response in 6 of 10 oestrous and 3 of 5 dioestrous mares. However, mating and teasing had no significant effect on concentrations of 15-keto-13,14-dihydro-PGF(2alpha) (PGFM). Manual manipulation of the clitoris, vagina and cervix caused significant OT release in all mares and intrauterine infusion of 500 ml PBS caused significant OT release in three of the five mares. However, only one mare had a significant PGF(2alpha) response during manual manipulation and only one responded positively to intrauterine infusion of 500 ml PBS. We concluded that events around mating, including stimulation of the genital tract and uterine distension, often caused an increase in circulating concentrations of OT but only rarely in PGFM.

The effect of opioid antagonism and environmental restriction on plasma oxytocin and vasopressin concentrations in parturient gilts.

Oxytocin plays an important role at parturition due to its involvement in uterine contractions, foetal expulsion and the onset of maternal behaviour. The role of the related neurohypophysial hormone, vasopressin, is less clear; however, there is some evidence that it is also involved in maternal behaviour and its role in osmotic regulation is well established. The aim of this study was to investigate the inhibitory effects of endogenous opioids on these hormones during the expulsive phase of parturition in the pig, and to examine how opioid restraint interacts with environmental restriction. The subjects of this study were 31 Large Whitex Landrace primiparous sows (gilts). An indwelling jugular catheter was implanted under general anaesthesia at 12 days before the expected parturition day (EPD). From 5 days before the EPD 15 of the gilts were individually housed in a restrictive parturition crate without straw and 16 were individually housed in a straw-bedded pen. Blood samples were taken with increasing frequency towards and during parturition through a catheter extension to reduce disturbance. At 7.5 min after the birth of the first piglet half of the gilts in each environment received a dose of the opioid receptor antagonist naloxone (1 mg/kg, i.v.) with the remaining gilts receiving saline as a control. Overall, there was no effect of environment on either circulating oxytocin or vasopressin. However, both oxytocin and vasopressin were inhibited by endogenous opioids during the expulsive phase. The inhibitory effects of opioids on these hormones did not appear to have any adverse effects on the progress of parturition as judged by cumulative piglet birth intervals. The regulation of the opioid inhibition of oxytocin and vasopressin during parturition is discussed in relation to other neurotransmitters and whether opioid inhibition of these neurohypophysial hormones is part of the 'normal' physiological response to parturition or whether it is stress-induced.

Anterior cruciate ligament reconstruction in adolescents with open physes.

The purpose of this study was to evaluate anterior cruciate ligament reconstructions performed in adolescents with open physes and a skeletal age of at least 14 years. At one center, from 1992 to 1996, 19 adolescents (ages, 11 to 15 years) with open physes and a skeletal age of at least 14 years underwent arthroscopic anterior cruciate ligament reconstruction using an Achilles tendon allograft placed through drill holes across the open physes in both the distal femur and proximal tibia. Fifteen patients returned for reevaluation at an average of 25 months postoperatively (range, 12 to 60 months); the remaining four patients were interviewed by telephone. There were no significant leg-length discrepancies or angular deformities as determined by scanograms and anteroposterior and lateral radiographs of the femur and tibia. The mean Lysholm knee score was 97 (range, 94 to 100) and the mean KT-1000 arthrometer side-to-side difference at 20 pounds of anterior force was 1.7 mm (range, 0.0 to 3.0). All patients were satisfied with the results of surgery, and 16 of 19 patients returned to the same sport they were participating in before the injury. This study demonstrates that anterior cruciate ligament reconstruction using an Achilles tendon allograft is a viable treatment option for skeletally immature patients with a skeletal age of 14 years who have sustained midsubstance tears of the anterior cruciate ligament.

The timing of parturition in the pig is altered by intravenous naloxone.

This experiment tested the hypothesis that opioid antagonists could influence the timing of the onset and progress of parturition in the pig. Primiparous pigs (gilts) received a jugular catheter on Days 104 to 106 of pregnancy. At 1400 h on Day 112 the gilts received 10 mg PGF2alpha, i.m. to induce parturition. At 1000 h on Day 113 (i.e., 20 h later) gilts received either saline (n=6), 1 mg/kg, i.v. naltrexone (n=4) or 1 mg/kg, i.v. naloxone (n=5). Blood samples were taken daily from Days 108 to 116. On Day 113, blood samples were taken hourly from 0500 to 0900 h and then every 30 min until 2400 h, or until the birth of the last piglet (BLP) (whichever was sooner) and assayed for progesterone, oxytocin (OT), cortisol and PRL. Additional blood samples for OT and cortisol assay were taken every minute from 0930 to 1100 h on Day 113 and for 30 min during parturition. Naloxone, but not naltrexone, delayed the onset of parturition relative to saline controls (by 14 h 21 min; P<0.05). Duration of parturition and rate of births were not significantly affected by treatment. Mean plasma OT increased in the 4 h following naloxone but not saline treatment, during which time OT plasma pulse amplitude was reduced in naloxone and naltrexone-treated animals relative to saline treated controls. The PRL secretion rose following treatment in saline treated animals, consistent with approaching parturition, but failed to rise in opioid antagonist treated animals. Progesterone concentrations remained elevated in naloxone-treated animals for longer than in the other groups. These data suggest that a rapid change in overall effect of parenteral administration of naloxone to parturient pigs occurs from delaying its onset when administered as in these experiments, to facilitating its progress when given during parturition (earlier experiments). The delay of onset of parturition may be mediated by interference with hypothalamic control of OT or PRL release.