Glucagon prescribing and prevention of hospitalization for hypoglycemia in a large health system.

AIMS: To examine glucagon prescribing trends among patients at high risk of severe hypoglycemia and assess if a glucagon prescription is associated with lower rates of severe hypoglycemia requiring hospital care. METHODS: Retrospective analysis of electronic health records from a large integrated healthcare system between May 2019 and August 2021. We included adults (≥18 years) with type 1 diabetes or with type 2 diabetes treated with short-acting insulin and/or recent history of hypoglycemia-related emergency department visit or hospitalization. We calculated rates of glucagon prescribing overall and by patient characteristics. We then matched 1:1 those who were and were not prescribed glucagon and assessed subsequent hypoglycemia-related hospitalization. RESULTS: Of 9,200 high risk adults, 2063 (22.4%) were prescribed glucagon. Among patients more likely to be prescribed glucagon were those younger, female, White, living in urban areas, with prior severe hypoglycemia, and with a recent endocrinology specialist visit. In the matched cohort (N = 1707 per arm), 62 prescribed glucagon and 33 not prescribed glucagon were hospitalized for hypoglycemia (adjusted incidence rate ratio 1.71, 95% CI 1.10-2.66; P = 0.018). CONCLUSION: Glucagon prescribing was infrequent with significant racial and rural disparities. Patients with glucagon prescriptions did not have lower rates of hospitalization for hypoglycemia.

Predictors of acarbose therapeutic efficacy in newly diagnosed type 2 diabetes mellitus patients in China.

BACKGROUND: Acarbose is one of the optimal drugs for patients with the first diagnosis of type 2 diabetes mellitus (T2DM). But what kind of emerging patients has the best therapeutic response to acarbose therapy has never been reported. To this end, we investigated predictors of acarbose therapeutic efficacy in newly diagnosed T2DM patients in China. METHODS: A total of 346 T2DM patients received acarbose monotherapy for 48 weeks as part of participating in the Study of Acarbose in Newly Diagnosed Patients with T2DM in China (MARCH study) from November 2008 to June 2011. Change in glycated hemoglobin (ΔHbA1c) served as a dependent variable while different baseline variables including sex, age, disease duration, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1c, fasting plasma glucose (FPG), 2-h postprandial blood glucose (2 h PG), fasting insulin (FINS), 2-h postprandial insulin (2 h INS), early insulin secretion index (IGI), homeostasis model assessment of insulin resistance index (HOMA-IR), homeostasis model assessment of beta cell function (HOMA-B), area under the curve (AUC) of glucagon, insulin and GLP-1 were assessed as independent predictors. Step-wise multiple linear regression was employed for statistical analysis. RESULTS: The results suggested that independent predictors of ΔHbA1c at 12 weeks included baseline body weight (ß = - 0.012, P = 0.006), DBP (ß = 0.010, P = 0.047), FPG (ß = 0.111, P = 0.005) and 2 h PG (ß = 0.042, P = 0.043). Independent predictors of ΔHbA1c at 24 weeks included disease duration (ß = 0.040, P = 0.019) and FPG (ß = 0.117, P = 0.001). Finally, independent predictor of ΔHbA1c at 48 weeks was disease duration (ß = 0.038, P = 0.046). CONCLUSIONS: Acarbose may be more effective in newly diagnosed T2DM patients with low FPG, low 2 h PG and obesity. The earlier T2DM is diagnosed and continuously treated with acarbose, the better the response to therapy.

Cyclocarya paliurus triterpenoids suppress hepatic gluconeogenesis via AMPK-mediated cAMP/PKA/CREB pathway.

BACKGROUND: Abnormal enhancement of hepatic gluconeogenesis is a vital mechanism of the pathogenesis of Type 2 diabetes mellitus (T2DM); thus, its suppression may present an efficient therapeutic strategy for T2DM. Cyclocarya paliurus (CP), a plant species native to China, has been reported to have anti-hyperglycemia activity. Our previous studies have revealed that Cyclocarya paliurus triterpenic acids (CPT) exert the favorable glucose-lowering activity, but the regulatory effect of CPT on hepatic gluconeogenesis is still unclarified. PURPOSE: This study aimed to investigate the potential role and mechanism of CPT in gluconeogenesis. STUDY DESIGN: In this study, the ameliorative effect and underlying mechanism of CPT on gluconeogenesis were investigated: high-fat diet and streptozotocin-induced T2DM mice and glucagon-challenged mouse primary hepatocytes. METHODS: T2DM model mice with or without oral administration of CPT for 4 weeks were monitored for body weight, glucose and lipid metabolism. Hematoxylin and eosin staining was used to observe liver lipid deposition. Real-time PCR assays were performed to examine the mRNA expression of glucose-6-phosphate (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes involved in liver gluconeogenesis. Western blotting was used to determine AMP-dependent protein kinase (AMPK) expression and induction of the glucagon signaling pathway. The possible mechanism of CPT on liver gluconeogenesis was further explored in glucagon-induced mouse primary hepatocytes. RESULTS: In vivo and in vitro experiments revealed that CPT treatment significantly reduced fasting blood glucose, total cholesterol and triglyceride levels, and improved insulin resistance. Furthermore, CPT could obviously decreased the mRNA and protein expression of G6Pase and PEPCK, the cyclic AMP content, the phosphorylation level of protein kinase A and cyclic AMP response element-binding protein. But CPT promoted the phosphorylation of AMP-dependent protein kinase (AMPK) and activation of phosphodiesterase 4B. Mechanistically, intervention with Compound C (an AMPK inhibitor) partially blocked the suppressive effect of CPT on hepatic gluconeogenesis. CONCLUSION: These findings suggested that CPT may inhibit hepatic gluconeogenesis against T2DM by activating AMPK.

Modern understanding of intussusception and recent trends in management / A gyermekkori invaginatio modern értelmezése és kezelése

Intussusception is one of the most common abdominal emergencies in children. The understanding of its aetiology and management has changed significantly over the last decades. Earlier, the hypertrophic Peyer's patches and polyps were considered responsible, but with the knowledge obtained from the lipopolysaccharide-induced animal model of intussusception, the rotavirus vaccination, the seasonality and the postnatal changes of the enteric nervous system it became clear that the intestinal motility plays a key role in the aetiology. The efficacy of non-operative management is continuously improving. The radiologists initially moved from the hydrostatic X-ray-controlled reduction towards the air enema (pneumatic reduction), however, nowadays, there is a shift back to hydrostatic procedures but under ultrasound guidance to reduce radiation exposure. In many institutions, intussusception is managed as day-case rather than as an inpatient case. The role of medications like glucagon and cyclo-oxygenase inhibitors used during reduction manoeuvres and prevention of recurrence is still controversial. Surgical management is shifting towards laparoscopy. The authors herein reviewed the current literature to present recent insights into understanding the pathogenesis and management updates. Orv Hetil. 2020; 161(32): 1331-1338.

Therapeutic approach of anaphylaxis.

PURPOSE OF REVIEW: Anaphylaxis is a recognized cause of death in all ages, which requires prompt recognition and treatment. We here propose to review the current and new pharmacological treatment of anaphylaxis in the view of the new knowledge in the field that can support the quality practice and empower allergists and health professionals with new tools that can be used to treat symptoms and prevent anaphylaxis. RECENT FINDINGS: The recent description of phenotypes provides new insight and understanding into the mechanisms and causes of anaphylaxis through a better understanding of endotypes and application of precision medicine. Several biologic therapies and new devices are emerging as potential preventive treatment for anaphylaxis. SUMMARY: Adrenaline (epinephrine) is still the first-line treatment for any type of anaphylaxis and is recognized as the only medication documented to prevent hospitalizations, hypoxic sequelae and fatalities. ß2-adrenergic agonists and glucagon remains as the second-line treatment of anaphylaxis, meanwhile glucocorticoids and antihistamines should be used only as third-line treatment. Their administration should never delay adrenaline injection in anaphylaxis. More intuitive adrenaline autoinjectors design and features are required as well as a worldwide availability of adrenaline autoinjectors. Biological drugs, such as omalizumab, have been used as therapeutic adjuvants as a preventive treatment of anaphylaxis, but cost-effectiveness should be considered individually. Understanding the specifications of underlying mechanisms can potentially support improvements in the patients' allergological work-up and open the opportunity of developments of potential new drugs, such as biological agents. Expanding knowledge with regard to the presentation, causes, and triggers for anaphylaxis among healthcare providers will improve its diagnosis and management, increase patient safety, and decrease morbidity and mortality.

Intranasal glucagon for hypoglycaemia in diabetic patients. An old dream is becoming reality?

In 1983 it was shown that glucagon administered intranasally (IN) was absorbed through the nasal mucosa and increased blood glucose in healthy subjects. Shortly thereafter, it was shown that IN glucagon counteracts with hypoglycaemia in insulin-treated diabetic patients. In spite of this evidence, IN glucagon was not developed by any pharmaceutical company before 2010, when renewed interest led to intensive evaluation of a possible remedy for hypoglycaemia in insulin-treated diabetic adults and children. IN glucagon is now being developed as a needle-free device that delivers glucagon powder for treatment of severe hypoglycaemia; the ease of using this device stands in stark contrast to the difficulties encountered in use of the current intramuscular glucagon emergency kits. Studies have demonstrated the efficacy, safety and ease-of-use of this IN glucagon preparation, and suggest IN glucagon as a promising alternative to injectable glucagon for treating severe hypoglycaemia in children and adults who use insulin. This would meet the unmet medical need for an easily administered glucagon preparation.

Management for intussusception in children.

BACKGROUND: Intussusception is a common abdominal emergency in children with significant morbidity. Prompt diagnosis and management reduces associated risks and the need for surgical intervention. Despite widespread agreement on the use of contrast enema as opposed to surgery for initial management in most cases, debate persists on the appropriate contrast medium, imaging modality, pharmacological adjuvant, and protocol for delayed repeat enema, and on the best approach for surgical management for intussusception in children. OBJECTIVES: To assess the safety and effectiveness of non-surgical and surgical approaches in the management of intussusception in children. SEARCH METHODS: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library; Ovid MEDLINE (1950 to September 2016); Ovid Embase (1974 to September 2016); Science Citation Index Expanded (via Web of Science) (1900 to September 2016); and BIOSIS Previews (1969 to September 2016).We examined the reference lists of all eligible trials to identify additional studies. To locate unpublished studies, we contacted content experts, searched the World Health Organization International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (September 2016), and explored proceedings from meetings of the British Association of Paedatric Surgeons (BAPS), the American Soceity of Pediatric Surgery, and the World Congress of Pediatric Surgery. SELECTION CRITERIA: We included all randomised controlled trials comparing contrast media, imaging modalities, pharmacological adjuvants, protocols for delayed repeat enema, and/or surgical approaches for the management of intussusception in children. We applied no language, publication date, or publication status restrictions. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted study selection and data extraction and assessed risk of bias using a standardised form. We resolved disagreements by consensus with a third review author when necessary. We reported dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs). We analysed data on an intention-to-treat basis and evaluated the overall quality of evidence supporting the outcomes by using GRADE criteria. MAIN RESULTS: We included six randomised controlled trials (RCTs) with a total of 822 participants. Two trials compared liquid enema reduction plus glucagon versus liquid enema alone. One trial compared liquid enema plus dexamethasone versus liquid enema alone. Another trial compared air enema plus dexamethasone versus air enema alone, and two trials compared use of liquid enema versus air enema. We identified three ongoing trials.We judged all included trials to be at risk of bias owing to omissions in reported methods. We judged five of six trials as having high risk of bias in at least one domain. Therefore, the quality of the evidence (GRADE) for outcomes was low. Interventions and data presentation varied greatly across trials; therefore meta-analysis was not possible for most review outcomes. Enema plus glucagon versus enema alone It is uncertain whether use of glucagon improves the rate of successful reduction of intussusception when compared with enema alone (reported in two trials, 218 participants; RR 1.09, 95% CI 0.94 to 1.26;low quality of evidence). No trials in this comparison reported on the number of children with bowel perforation(s) nor on the number of children with recurrent intussusception. Enema plus dexamethasone versus enema alone Use of the adjunct, dexamethasone, may be beneficial in reducing intussusception recurrence with liquid or air enema (two trials, 299 participants; RR 0.14, 95% CI 0.03 to 0.60; low quality of evidence). This equates to a number needed to treat for an additional beneficial outcome of 13 (95% CI 8 to 37). It is uncertain whether use of the adjunct, dexamethasone, improves the rate of successful reduction of intussusception when compared with enema alone (reported in two trials, 356 participants; RR 1.01, 95% CI 0.92 to 1.10;low quality of evidence). Air enema versus liquid enema Air enema may be more successful than liquid enema for reducing intussusception (two trials, 199 participants; RR 1.28, 95% CI 1.10 to 1.49; low quality of evidence). This equates to a number needed to treat for an additional beneficial outcome of 6 (95% CI 4 to 19). No trials in this comparison reported on the number of children with bowel perforation(s) or on the number of children with recurrent intussusception nor any intraoperative complications, such as bowel perforation, or other adverse effects. Only one trial reported postoperative complications, but owing to the method of reporting used, a quantitative analysis was not possible. We identified no studies that exclusively evaluated surgical interventions for management of intussusception. AUTHORS' CONCLUSIONS: This review identified a small number of trials that assessed a variety of interventions. All included trials provided evidence of low quality and were subject to serious concerns about imprecision, high risk of bias, or both. Air enema may be superior to liquid enema for successfully reducing intussusception in children; however, this finding is based on a few studies including small numbers of participants. Dexamethasone as an adjuvant may be more effective in reducing intussusception recurrence rates following air enema or liquid enema, but these results are also based on a few studies of small numbers of participants. This review highlights several points that need to be addressed in future studies, including reducing the risk of bias and including relevant outcomes. Specifically, surgical trials are lacking, and future research is needed to address this evidence gap.

Assessment of Nifedipine Therapy in Hyperinsulinemic Hypoglycemia due to Mutations in the ABCC8 Gene.

CONTEXT: Previous case reports have documented the effectiveness of l-type calcium channel blockers (such as nifedipine and verapamil) for treating different forms of hyperinsulinemic hypoglycemia (HH). OBJECTIVE: To systematically assess the glycemic response to nifedipine therapy in 11 patients with HH due to mutations in the ABCC8 gene. DESIGN: Dose escalation of nifedipine therapy. SETTINGS AND PATIENTS: Eleven children who were inpatients at a tertiary hospital and had diazoxide unresponsive HH due to mutations in the ABCC8 gene. INTERVENTION(S): Nifedipine was administered orally at an escalating dose up to a maximum of 2.5 mg/kg/d. MAIN OUTCOME MEASURES: Improvement in glycemic control, avoidance of hypoglycemic episodes, reduction of intravenous glucose infusion, and reduction in the requirements of other medical therapies. RESULTS: The median age of the patients was 0.44 years (range 0.14 to 3.77). The ABCC8 gene mutations were homozygous in 3 cases, paternally inherited heterozygous in 4, and compound heterozygous in 4. 18F-DOPA PET/CT scan demonstrated a focal lesion in 2 cases and the rest were diffuse HH disease. One subject had nifedipine as monotherapy, whereas the rest had it in combination with octreotide/glucagon/diazoxide or cornstarch. After a median of 6.5 (3 to 23) days of maximal (2.5 mg/kg/d) dose of nifedipine therapy, none of the patients showed any improvement in glycemic control and patients continued to have hypoglycemic episodes. CONCLUSIONS: HH due to mutations in the ABCC8 gene does not respond to nifedipine therapy. Mutations in the KATP channel genes might render the l-type calcium channel ineffective to therapy with nifedipine.

Congenital hyperinsulinism: exclusive human milk and breastfeeding.

Congenital hyperinsulinism is a genetic condition causing dysregulation of insulin and results in persistent hypoglycemia. The most common types are sulfonylurea receptor (SUR1), potassium inward rectifying channel (Kir6.2), glutamate dehydrogenase (GDH), and glucokinase (GK), with SUR1 and Kir6.2 being the most prevalent. It is imperative that these infants undergo diagnostic testing, which includes genetic, neonatal fasting study to induce hypoglycemia, glucagon stimulation, and imaging. Once a diagnosis has been made, surgical intervention may be needed to help regulate blood glucose levels. During this diagnostic process and as the infant is undergoing treatment, there may be little concern for the mother's feeding plan. Because human milk is the preferred form of nutrition for all infants, these mothers should receive prenatal counseling regarding the initiation and maintenance of milk supply. Parenteral nutrition may be necessary to maintain blood glucose to support human milk administration and breastfeeding.

Management of a mixed overdose of calcium channel blockers, ß-blockers and statins.

We describe a case of extreme mixed overdose of calcium channel blockers, ß-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and ß-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness.

GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet.

We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog in combination with exendin-4 or FGF21. However, the return of leptin action required discontinuation of high-fat diet (HFD) exposure. Here we assess whether a single peptide possessing balanced coagonism at the glucagon-like peptide 1 (GLP-1) and glucagon receptors can restore leptin responsiveness in DIO mice maintained on a HFD. DIO mice were treated with PEG-GLP-1/glucagon (30 nmol/kg every fourth day) to induce an ∼15% body weight loss, upon which they were randomized to continue PEG-GLP-1/glucagon therapy or reassigned to receive supplemental daily PEG-leptin (185 nmol/kg/day). The addition of PEG-leptin to PEG-GLP-1/glucagon resulted in an ∼18% greater weight loss as compared with PEG-GLP-1/glucagon alone and was accompanied by further decreases in food intake and improved glucose and lipid metabolism. The beneficial effect of PEG-leptin supplementation occurred after an initial body weight loss similar to what we previously reported following reduced dietary fat along with PEG-leptin and exendin-4 or FGF21 cotreatment. In summary, we report that GLP-1/glucagon coagonism restores leptin responsiveness in mice maintained on a HFD, thus emphasizing the translational value of this polypharmacotherapy for the treatment of obesity and diabetes.

[Treatment of foreign body impactions in oesophagus]. / Håndtering af fremmedlegeme i øsofagus med synkestop.

Foreign body impactions in oesophagus occur frequently. The causes are oesophageal pathology (anatomical, functional or inflammatory diseases). X-ray may be performed to determine the diagnosis or suspected perforation. Treatment can be conservative with carbonated drinks and observation for up to 24 hours, as up to two thirds of the impactions pass spontaneously. There is no evidence for medical treatment with buscopane, diazepam or glucagone. Emergent endoscopy is performed at risk of perforation by erosive or sharp objects, by obstruction over 24 hours, at risk of aspiration and complete obstruction.

Management of lercanidipine overdose with hyperinsulinaemic euglycaemia therapy: case report.

This case report describes the first reported overdose of the dihydropyridine calcium channel blocker (CCB) lercanidipine. A 49 yr old male presented to the Emergency Department 3 hrs after the ingestion of 560 mg of lercanidipine. In the department he had a witnessed seizure within 15 minutes of arrival attributed to the overdose. Following immediate recovery of consciousness after the seizure, he had refractory hypotension and bradycardia which failed to respond to fluid resuscitation, glucagon therapy, and intravenous calcium. He went on to require vasopressor support with noradrenaline and was treated with high dose insulin therapy which was successful in achieving cardiovascular stability. Vasopressor therapy was no longer required within one half life of lercanidipine, and the total stay on intensive care was one day before transfer to a ward.Calcium channel blocker overdose is an uncommon but life-threatening overdose. Treatment for severe toxicity is similar to b-blocker overdose. Hypotension is treated with intravenous fluid therapy, intravenous calcium and possibly glucagon with vasopressor or inotropic support as required. Atropine is used to attempt reversal of bradycardia. High doses of intravenous insulin with intravenous dextrose as required (hyperinsulinaemic euglycaemia or HIET), has also been successfully reported. Experimental animal data suggests that HIET is of benefit and potentially superior to fluid therapy, calcium, glucagon and potentially vasopressor therapy. HIET effectively and sustainably reverses hypotension, bradycardia and improves myocardial contractility and metabolism. Current advice in calcium channel blocker overdose is to begin therapy early in toxicity, starting with a 1.0 IU/kg insulin bolus followed by an infusion of 0.5 IU/kg/hr of insulin and dextrose as required titrated to clinical response.

Calcium channel blocker toxicity.

Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.

Prolonged severe hypotension following combined amlodipine and valsartan ingestion.

INTRODUCTION: Compared to other calcium channel blockers (CCBs), overdose with dihydropyridine CCBs are considered relatively benign due to their vascular selectivity. Although not a sustained-release preparation, amlodipine's prolonged duration of effect is concerning following overdose. In addition, angiotensin II receptor blocker blunting of vasoconstrictive and sympathetic compensatory responses could exacerbate calcium channel blocker toxicity. We describe severe toxicity associated with an overdose of amlodipine and valsartan. CASE REPORT: A 75-year-old woman presented to the ED 45 minutes after a witnessed suicidal ingestion of a "handful" of amlodipine and valsartan tablets. Hypotension, which appeared two hours after ingestion, was refractory to crystalloids and colloids, calcium gluconate, epinephrine, norepinephrine, phenylephrine, and vasopressin infusions. High-dose insulin euglycemia (HIE) therapy, and treatment with glucagon and naloxone were successful in improving her hemodynamic status. In this combined overdose, right heart catheterization demonstrated both negative inotropic effects and decreased systemic vascular resistance. CONCLUSION: Co-ingestion of amlodipine with valsartan produced profound toxicity. Early institution of HIE therapy may be beneficial to reverse these effects.

Estudio PET-TC con 18F-fluoro-L-DOPA combinado con el análisis genético para la optimización de la clasificación y tratamiento de un niño con hiperinsulinismo congénito grave / 18F-fluoro-L-DOPA PET-CT imaging combined with genetic analysis for optimal classification and treatment in a child with severe congenital hyperinsulinism

Fundamento: La distinción entre el hiperinsulinismo congénito (CHI) focal y difuso es esencial de cara al tratamiento y pronóstico de la enfermedad. El objetivo es presentar el primer caso de CHI focal diagnosticado en España combinando los estudios genético y PET-TC. Métodos: Paciente de 13 meses con CHI y pruebas de imagen convencionales normales, tratado con diazóxido, control dietético y alimentación por gastrostomía. Se analizó la secuencia de los genes ABCC8 y KCNJ11, y realizó una PET-TC con 18F-fluoro-L-DOPA. Resultados: Se detectó una mutación patogénica (G111R) en el alelo paterno de ABCC8. La PET-TC demostró un foco hipercaptante en el cuerpo del páncreas compatible con un adenoma confirmado histopatológicamente. Tras la cirugía el paciente continúa asintomático sin tratamiento farmacológico ni medidas dietéticas. Conclusiones: La combinación del análisis genético y la PET-TC con 18F-fluoro-L-DOPA muestra un gran potencial para la identificación, localización y guía de la cirugía del CHI (AU)

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy. The differential diagnosis between focal and diffuse forms of CHI is of great importance when planning surgery. The aim of this article is to show the first case of focal CHI diagnosed in Spain using PET-CT imaging combined with genetic analysis. Methods: A 13 month child with CHI and normal conventional radiological investigations treated with diazoxide, diet control and feeding by gastrostomy is presented. Genetic analysis of ABCC8 and KCNJ11 genes and PET-TAC using 18F-fluoro-L-DOPA were performed. Results: A pathological mutation (G111R) in the paternal allele of ABCC8 was detected. PET-CT scanning using 18F-fluoro-L-DOPA showed a focus of high uptake in the body of the pancreas compatible with adenoma that was hystopathologically confirmed. After surgical resection the patient is asymptomatic without needing either pharmacological treatment or dietetic control. Conclusions: The combination of genetic analysis and 18F-fluoro-L-DOPA PET-TAC shows a great potential for the identification, location and guideline for surgery in CHI (AU)

GLP-1. Generalidades e interacción incretinas-nutrientes / GLP-1 Generalities and incretin-nutrient interaction

Las incretinas son sustancias que se producen en el intestino y se liberan en respuesta a la ingestión oral de nutrientes, sobre todo hidratos de carbono, siendo poderosas secretagogas que aumentan la liberación de insulina. Las 2 hormonas incretinas más importantes son el polipéptido inhibidor gástrico (GIP) y el péptido-1 similar al glucagón (GLP-1). Además de estimular la secreción de insulina, el GLP-1 suprime la liberación de glucagón, enlentece el vaciamiento gástrico, mejora la sensibilidad a la insulina y reduce el consumo de alimentos. Otros nutrientes pueden estimular también la secreción de insulina, como son el ácido oleico y la proteína de suero. Hoy día se está desarrollando un nuevo arsenal terapéutico centrado en el papel de las incretinas para un mejor abordaje de la diabetes mellitus tipo 2 (DM 2) (AU)

Incretins are hormones produced in the intestine that are released in response to oral intake of nutrients, above all carbohydrates. They are powerful secretors that increase insulin release. The two most important incretin hormones are GIP (glucose-dependent insulinotropic peptide; also known as gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1). GLP-1 not only stimulates insulin secretion but also reduces glucagon release, slows gastric emptying, improves insulin sensitivity and increases satiety. Other nutrients may also stimulate insulin secretion: oleic acid and serum protein. Currently a new therapeutic armamentarium focused on the role of incretins is being developed to improve the treatment of type 2 diabetes mellitus (DM 2) (AU)

Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers.

PURPOSE: The toxic effects and treatment of beta-adrenergic blocker and calcium-channel blocker (CCB) overdose are reviewed. SUMMARY: Overdoses with cardiovascular drugs are associated with significant morbidity and mortality. Beta-blockers and CCBs represent the most important classes of cardiovascular drugs. In overdose, beta-blockers and CCBs have similar presentation and treatment overlaps and are often refractory to standard resuscitation measures. The common feature of beta-blocker toxicity is excessive blockade of the beta-receptors resulting in bradycardia and hypotension. Poisoning by CCBs is characterized by cardiovascular toxicity with hypotension and conduction disturbances, including sinus bradycardia and varying degrees of atrioventricular block. Therapies include beta-agonists, glucagon, and phosphodiesterase inhibitors. However, in beta-blocker poisoning where symptomatic bradycardia and hypotension are present, high-dose glucagon is considered the first-line antidote. Traditionally, antidotes for CCB overdose have included calcium, glucagon, adrenergic drugs, and amrinone. For cases of CCB poisoning where cardiotoxicity is evident, first-line therapy is a combination of calcium and epinephrine; high-dose insulin with supplemental dextrose and potassium therapy (HDIDK) is reserved for refractory cases. Health-system pharmacists should be aware that when these drugs are used as antidotes, higher than normal dosing is needed. CONCLUSION: Poisoning by beta-blockers or CCBs usually produces hypotension and bradycardia, which may be refractory to standard resuscitation measures. For cases of beta-blocker poisoning where symptomatic bradycardia and hypotension are present, high-dose glucagon is considered the first-line antidote. For cases of CCB poisoning where cardiotoxicity is evident, a combination of calcium and epinephrine should be used initially, reserving HDIDK for refractory cases.

Efficacy of peppermint oil as an antispasmodic during endoscopic retrograde cholangiopancreatography.

BACKGROUND: During endoscopic retrograde cholangiopancreatography (ERCP), hyoscine-N-butylbromide (Buscopan) or glucagon is used to inhibit duodenal motility. However, they may cause adverse effects. Peppermint oil has an antispasmodic effect and is used as a less hazardous antispasmodic during colonoscopy and upper gastrointestinal endoscopy. The purpose of the present paper was therefore to investigate peppermint as an antispasmodic for ERCP. METHODS: Forty patients were enrolled prospectively. They were assigned to four groups according to the peppermint oil concentration and site of administration: group 1, 20 mL of 1.6% solution around duodenal papilla; group 2, 20 mL of 1.6% solution both to the antrum of the stomach and around the duodenal papilla; group 3, 20 mL of 3.2% solution around the duodenal papilla; and group 4, 3.2% solution both to the antrum and around the duodenal papilla. Glucagon or hyoscine-N-butylbromide was added when duodenal peristalsis was not adequately diminished. Sixteen patients undergoing ERCP with glucagon were employed as historical controls. RESULTS: The ERCP was attempted in all except one patient in group 2 who had bleeding from invaded tumor to the duodenum. Peppermint administration equally reduced duodenal motility in the groups. Duodenal movement was none or mild in 69.2% of patients. The ERCP was successfully performed with peppermint alone in 91.4% of patients (37/39). Glucagon or hyoscine-N-butylbromide was needed in one patient each in groups 1 and 4. Serious complications related to peppermint oil did not occur. Inhibitory effect of peppermint appears to be identical to that of glucagon. CONCLUSION: Duodenal relaxation was obtained with 20 mL of 1.6% peppermint oil solution in the duodenum, but additional administration may be required. Peppermint oil is useful as an antispasmodic agent for ERCP.