1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the ability to reassert this activity following the temporary blockade of human beta2-adrenoceptors with antagonist. 2. We have compared the activation and desensitization of human beta2-adrenoceptor stimulation of adenylyl cyclase induced by salmeterol, adrenaline and salbutamol in a human lung epithelial line, BEAS-2B, expressing beta2-adrenoceptor levels of 40-70 fmol mg(-1), and in human embryonic kidney (HEK) 293 cell lines expressing 2-10 pmol mg(-1). The efficacy observed for the stimulation of adenylyl cyclase by salmeterol was only approximately 10% of that observed for adrenaline in BEAS-2B cells expressing low levels of beta2-adrenoceptor, but similar to adrenaline in HEK 293 cells expressing very high levels of receptors. Salmeterol pretreatment of these cells induced a rapid and stable activation of adenylyl cyclase activity which resisted extensive washing and beta2-adrenoceptor antagonist blockade, consistent with binding to a receptor exosite and/or to partitioning into membrane lipid. 3. The desensitization and internalization of beta2-adrenoceptors induced by the partial agonists salmeterol and salbutamol were considerably reduced relative to the action of adrenaline. Consistent with these observations, the initial rate of phosphorylation of the receptor induced by salmeterol and salbutamol was much reduced in comparison to adrenaline. 4. Our data suggest that the reduction in the rapid phase of desensitization of beta2-adrenoceptors after treatment with salmeterol or salbutamol is caused by a decrease in the rate of beta2-adrenoceptor kinase (betaARK) phosphorylation and internalization. In contrast, the rate of cyclic AMP-dependent protein kinase (PKA)-mediated phosphorylation by these partial agonists appears to be similar to adrenaline.

The chromaffin cell has been used as a model to characterize releasable components present in secretory granules and to understand the cellular mechanisms involved in catecholamine release. Recent physiological and biochemical developments have revealed that molecular mechanisms implicated in granule trafficking are conserved in all eukaryotic species: a rise in intracellular calcium triggers regulated exocytosis, and highly conserved proteins are essential elements which interact with each other to form a molecular scaffolding, ensuring the docking of granules at the plasma membrane, and perhaps membrane fusion. However, the mechanisms regulating secretion are multiple and cell specific. They operate at different steps along the life of a granule, from the time of granule biosynthesis up to the last step of exocytosis. With regard to cell specificity, noradrenaline and adrenaline chromaffin cells display different receptor and signaling characteristics that may be important to exocytosis. Characterization of regulated exocytosis in chromaffin cells provides not only fundamental knowledge of neurosecretion but is of additional importance as these cells are used for therapeutic purposes.

To investigate the effect of gender on catecholamine responses to hypoglycaemia, single-step euglycaemic-hypoglycaemic clamps have been performed in 14 healthy men and 17 women. Adrenaline responses were 44% lower in females (p < 0.01) and noradrenaline 17% lower (p = 0.08). In response to low-dose intravenous insulin infusion (0.3 mU.kg-1.min-1), plasma glucose fall and counterregulation in seven men and seven women had a different course (p < 0.001), with different glucose kinetics. In men, endogenous glucose output recovered quickly to levels that exceeded basal; in women suppression of endogenous glucose output was more prolonged, without rates ever exceeding basal (p < 0.05). Peripheral glucose uptake was stimulated in men only. The hormones of acute glucose counterregulation (catecholamines and glucagon) did not differ between the sexes during this challenge, the catecholamine response in the women being supported by the continuous fall in plasma glucose. These results suggest that: 1) catecholamine responses to moderately controlled hypoglycaemia are diminished in women, and 2) peripheral insulin sensitivity in men is enhanced over that of women but hepatic sensitivity to insulin may be greater in women.

1 Responses of preparations of human and porcine isolated bronchus and pulmonary artery to carbachol (CCh), methacholine, histamine, 5-hydroxytryptamine (5-HT), (-)-noradrenaline (NA), (-)adrenaline (Adr) and (+/-)-isoprenaline (Iso) were compared with responses to the same agonists in isolated lung parenchyma strips. 2 All preparations from both human and porcine lung contracted in response to histamine and all, except preparations of porcine pulmonary artery, contracted in response to CCh. Human and porcine pulmonary artery and parenchyma strip contracted in response to NA while bronchial preparations invariably relaxed. Iso caused relaxation of human and porcine bronchus and parenchyma strip. Although 5-HT was completely inactive in tissues isolated from pig lung, this amine was a powerful spasmogen in human pulmonary artery, relaxed human bronchus and caused variable responses in human parenchyma. 3 Results indicate that the pharmacological characteristics of human and porcine parenchyma strips may be explained in terms of responses of vascular or airways smooth muscle.

We have used the alpha1D-adrenoceptor selective antagonist, BMY 7378, the alpha1D-selective agonists, adrenaline and phenylephrine, the alpha1A-selective antagonists, (+)-niguldipine, SB 216469 and WB4101, and the non-subtype-selective alpha1-adrenoceptor antagonist, nemonapride, to investigate the presence of alpha1D-adrenoceptors in rat tissues at the protein level. Radioligand binding studies using [3H]prazosin as the radioligand were performed in three tissues containing alpha1D-adrenoceptor mRNA, spleen, cerebral cortex and kidney, and in comparison in one tissue not containing alpha1D-adrenoceptor mRNA, liver. Cerebral cortex and kidney were also studied upon alpha1B-adrenoceptor inactivation by chloroethylclonidine treatment (10 microM, 30 min, 37 degrees C). Experiments with cloned rat alpha1-adrenoceptor subtypes transiently expressed in COS cells confirmed the known selectivity of the investigated drugs for alpha1-adrenoceptor subtypes or the lack thereof of nemonapride. Accordingly nemonapride had steep and monophasic competition curves in all native and chloroethylclonidine-treated tissues. BMY 7378 also had steep and monophasic competition curves and low affinity in all native tissues. In contrast, adrenaline and phenylephrine (in the presence of 100 microM GTP) had monophasic competition curves of low affinity in liver and spleen but biphasic competition curves in cerebral cortex and kidney. Following chloroethylclonidine treatment competition curves for adrenaline, phenylephrine, (+)-niguldipine, SB 216469 and WB 4101 remained biphasic in cerebral cortex and kidney while those for nemonapride remained monophasic. We conclude that alpha1D-adrenoceptors are not readily detectable at the protein level in a variety of rat tissues where their mRNA is expressed. The biphasic competition curves of some agonists and antagonists in chloroethylclonidine-treated rat tissues do not represent alpha1D-adrenoceptors and are not readily explained by the present alpha1A/alpha1B/alpha1D-adrenoceptor classification.

Adipocytes contain high levels of S100B and in vitro assays indicate a modulated secretion of this protein by hormones that regulate lipolysis, such as glucagon, adrenaline, and insulin. A connection between lipolysis and S100B release has been proposed but definitive evidence is lacking. Although the biological significance of extracellular S100B from adipose tissue is still unclear, it is likely that this tissue might be an important source of serum S100B in situations related, or not, to brain damage. Current knowledge does not preclude the use of this protein in serum as a marker of brain injury or astroglial activation, but caution is recommended when discussing the significance of changes in serum levels where S100B may function as an adipokine, a neurotrophic cytokine, or an alarmin.

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studied in vitro on isolated rat blood vessels. The 10(-9)M NPY enhanced (about two-fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two-fold) in the femoral artery. Higher concentrations of NPY (greater than 10(-8)M) caused an adrenoceptor-resistant contraction per se. The TNS-evoked [3H]NA efflux was significantly reduced by NPY in a concentration-dependent manner (threshold 10(-9)M). The calcium antagonist, nifedipine, abolished the contractile effects of NPY and the NPY-induced enhancement of NA contractions but did not influence the prejunctional inhibition of [3H]NA release. Receptor-binding studies showed that the ratio of alpha 1-to alpha 2-adrenoceptors in the femoral artery was 30:1. The NPY did not cause any detectable change in the number of alpha 1-or alpha 2-adrenoceptor binding sites or in the affinity of alpha 2-binding sites, as revealed by prazosin- and clonidine-binding, respectively. The NPY also inhibited the TNS-evoked [3H]NA release (by 42-86%) in the superior mesenteric and basilar arteries and in femoral and portal veins. The NPY still depressed TNS-evoked [3H]NA secretion from the portal vein in the presence of phentolamine. The NPY caused a clear-cut contraction in the basilar artery, increased the contractile force of spontaneous contractions in the portal vein, while only weak responses were observed in the superior mesenteric artery and femoral vein. The NA-induced contraction was markedly enhanced by NPY in the superior mesenteric artery, only slightly enhanced in the portal vein and uninfluenced in the femoral vein. In conclusion, in all blood vessels tested, NPY depresses the TNS-evoked [3H]NA secretion via a nifedipine-resistant action. Furthermore, NPY exerts a variable, Ca2+-dependent vasoconstrictor effect and enhancement of NA and TNS contractions.

Many hormones interact with receptors which stimulate the enzyme adenylate cyclase. Less well characterized ar those receptors which mediate an inhibition of adenylate cyclase activity. However, guanine nucleotides are clearly important in the regulation of both stimulatory and inhibitory receptors. Monovalent cations, notably Na+, regulate many inhibitory receptor systems but apparently not stimulatory receptors. We investigate here the effects of Na+ and guanine nucleotides on the adenylate cyclase-coupled inhibitory alpha 2-adrenergic receptor of the rabbit platelet. Computer modelling of adrenaline competition curves with 3H-dihydroergocryptine (3H-DHE) indicates that adrenaline induces two distinct affinity states of the alpha 2 receptor--one of higher (alpha 2H) and the other of lower (alpha 2L) affinity. Guanyl-5'-yl-imidodiphosphate (Gpp(NH)p) seems to reduce adrenaline affinity to converting the high-affinity state into the low-affinity form of the receptor. In contrast, Na+ reduces adrenaline affinity at both the high- and low-affinity states of the alpha 2 receptor while preserving receptor heterogeneity. Thus, guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the alpha 2-adrenergic receptor.

The relationship between thermoreception, hormonal secretion and muscular activity was studied. 6 men swam 60 min in 21, 27 and 33 degrees C water at a speed requiring 68% of VO2 max (determined in 27 degrees C water). Rectal temperature increased in 33 degrees C (1.3 +/- 0.2 degrees C, mean and S.E.) and 27 degrees C (0.7+/- 0.1 degrees C) expts. but decreased in 21 degrees C expts. (0.8 +/- 0.3 degrees C). Changes in esophageal and muscle temperatures parallelled changes in rectal temperature. Plasma noradrenaline was higher in 33 degrees C than in 27 degrees C expts. and growth hormone, cortisol and glucagon concentrations increased in 27 degrees C and 33 degrees C expts. only. Insulin concentrations were uniformly depressed during swimming at the different water temperatures. In 21 degrees C expts. noradrenaline and adrenaline concentrations were higher than in 27 degrees C expts. VO2, carbohydrate combustion and peak lactate were slightly lower in 33 degrees C expts. Plasma glucose decreased slightly and FFA and glycerol concentrations increased identically in all expts. Heart rate increased continuously during swimming in 27 degrees C and 33 degrees C expts., but not in 21 degrees C expts. In conclusion the rise in body temperatures normally observed during exercise enhances the exercise induced increases in the plasma concentrations of noradrenaline, cortisol, growth hormone and glucagon. Decreased body temperatures may elicit catecholamine secretion as a direct consequence of thermoreception. Shivering may account for previously observed decreases in insulin secretion during cold stress but not for increases in cortisol and growth hormone.

The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2-4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3-8 months) 4-60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2-4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20-30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.

L-adrenaline belongs to a group of the compounds known as catecholamines, which play an important role in the regulation of physiological process in living organisms. The antioxidant activity and antioxidant mechanism of L-adrenaline was clarified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD(+)), and superoxide anion radicals (O(2)(-)) scavenging activity, hydrogen peroxide (H(2)O(2)), total antioxidant activity, ferric ions (Fe(3+)) and cupric ions (Cu(2+)) reducing ability, ferrous ions (Fe(2+)) chelating activity. L-adrenaline inhibited 74.2% lipid peroxidation of a linoleic acid emulsion at 30 microg/mL concentration. On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol and trolox displayed 83.3, 82.1, 68.1 and 81.3% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. BHA, BHT, alpha-tocopherol and trolox were used as reference antioxidants and radical scavenger compounds. Moreover, this study will bring an innovation for further studies related to antioxidant properties of L-adrenaline. According to present study, L-adrenaline had effective in vitro antioxidant and radical scavenging activity.

26 patients with suspected phaeochromocytoma underwent selective venous sampling: a tumour was identified and removed in 18.4 of these patients did not have sustained hypertension, and the only persistent abnormality was an elevated plasma-adrenaline level. The increased plasma-catecholamine concentrations in the tumour patients were not suppressed by pentolinium 2.5 mg i.v., whereas the levels in the 8 non-tumour patients were lowered to the normal range. Calculations based on the arteriovenous differences of adrenaline and noradrenaline suggest that adrenal medullary secretion contributed less than 2% of circulating noradrenaline in the non-tumour patients. Plasma-adrenaline, however, is derived almost entirely from the adrenal gland, and its estimation appears superior to that of noradrenaline in the detection of a small adrenal phaeochromocytoma.

1. To evaluate the role of adrenaline in regulating carbohydrate metabolism during moderate exercise, 10 moderately trained men completed two 20 min exercise bouts at 58 +/- 2 % peak pulmonary oxygen uptake (V(O2,peak)). On one occasion saline was infused (CON), and on the other adrenaline was infused intravenously for 5 min prior to and throughout exercise (ADR). Glucose kinetics were measured by a primed, continuous infusion of 6,6-[(2)H]glucose and muscle samples were obtained prior to and at 1 and 20 min of exercise. 2. The infusion of adrenaline elevated (P < 0.01) plasma adrenaline concentrations at rest (pre-infusion, 0.28 +/- 0.09; post-infusion, 1.70 +/- 0.45 nmol l(-1); means +/- S.E.M.) and this effect was maintained throughout exercise. Total carbohydrate oxidation increased by 18 % and this effect was due to greater skeletal muscle glycogenolysis (P < 0.05) and pyruvate dehydrogenase (PDH) activation (P < 0.05, treatment effect). Glucose rate of appearance was not different between trials, but the infusion of adrenaline decreased (P < 0.05, treatment effect) skeletal muscle glucose uptake in ADR. 3. During exercise muscle glucose 6-phosphate (G-6-P) (P = 0.055, treatment effect) and lactate (P < 0.05) were elevated in ADR compared with CON and no changes were observed for pyruvate, creatine, phosphocreatine, ATP and the calculated free concentrations of ADP and AMP. 4. The data demonstrate that elevated plasma adrenaline levels during moderate exercise in untrained men increase skeletal muscle glycogen breakdown and PDH activation, which results in greater carbohydrate oxidation. The greater muscle glycogenolysis appears to be due to increased glycogen phosphorylase transformation whilst the increased PDH activity cannot be readily explained. Finally, the decreased glucose uptake observed during exercise in ADR is likely to be due to the increased intracellular G-6-P and a subsequent decrease in glucose phosphorylation.

OBJECTIVE

The aim was to investigate the influence of long term dietary fish oil consumption on cardiac function in a non-human primate, to elucidate further the basis of the apparently reduced cardiovascular disease mortality associated with its consumption in man.

METHODS

Adult male marmoset monkeys (Callithrix jacchus) were fed diets supplemented with polyunsaturated fatty acids (PUFA) of marine (tuna fish oil) or plant (sunflower seed oil) origin, saturated animal fat (sheep perirenal fat), or a low fat reference diet for 24 months. Cardiac function was assessed using radionuclide angiography under pentobarbitone anaesthesia with a counts based adaptation for ventricular volume estimations. Measures were made at rest and during infusion of adrenaline.

RESULTS

The mean left ventricular ejection fraction was greater in the tuna fish oil group [55.0(SEM 1.1)% n = 7] and the sunflower seed oil group [58.1(2.4)% n = 8] than in the reference group [48.5(1.4)% n = 9] and the sheep fat group [47.6(1.8)% n = 8]. This was associated with a more than 25% greater end diastolic volume and 40-70% increases in stroke volume in tuna fish or sunflower seed oil fed animals. There was no evidence of cardiac hypertrophy. In contrast, adrenaline increased stroke volume and ejection fraction by increasing emptying, thus reducing residual end systolic. Tuna fish oil fed animals had a low resting heart rate. When this was raised to comparable levels by adrenaline, lower pressure-rate indices and greater cardiac minute work suggested higher myocardial energy efficiency in PUFA fed animals compared with the reference and sheep fat groups.

CONCLUSIONS

Dietary fish oil and sunflower seed oil increased the left ventricular ejection fraction in the marmoset monkey by enhancing ventricular filling, thus providing an energy sparing promotion of diastolic relaxation.

Vitiligo surgery is an effective method of treatment for selected, resistant vitiligo patches in patients with vitiligo. PHYSICIAN'S QUALIFICATIONS: The physician performing vitiligo surgery should have completed postgraduate training in dermatology which included training in vitiligo surgery. If the center for postgraduation does not provide education and training in cutaneous surgery, the training may be obtained at the surgical table (hands-on) under the supervision of an appropriately trained and experienced dermatosurgeon at a center that routinely performs the procedure. Training may also be obtained in dedicated workshops. In addition to the surgical techniques, training should include local anesthesia and emergency resuscitation and care.

METHODS

Vitiligo surgery can be performed safely in an outpatient day care dermatosurgical facility. The day care theater should be equipped with facilities for monitoring and handling emergencies. A plan for handling emergencies should be in place, with which all nursing staff should be familiar. Vitiligo grafting for extensive areas may need general anesthesia and full operation theater facility in a hospital setting and the presence of an anesthetist is recommended in such cases. INDICATIONS FOR VITILIGO SURGERY: Surgery is indicated for stable vitiligo that does not respond to medical treatment. While there is no consensus on definitive parameters for stability, the Task Force suggests the absence of progression of disease for the past one year as a definition of stability. Test grafting may be performed in doubtful cases to detect stability.

METHODS

A detailed consent form elaborating the procedure and possible complications should be signed by the patient. The patient should be informed of the nature of the disease and that the determination of stability is only a vague guide. The consent form should specifically state the limitations of the procedure, about the possible future progression of disease and whether more procedures will be needed for proper results. The patient should be provided with adequate opportunity to seek information through brochures and one-to-one discussions. The need for concomitant medical therapy should be emphasized and the patient should understand that proper results take time (a few months to a year). Preoperative laboratory studies include hemogram including platelet counts, bleeding and clotting time (or prothrombin and activated partial thromboplastin time), and blood chemistry profile. Screening for antibodies for hepatitis B surface antigen and HIV is recommended depending on individual requirements.

METHODS

Lignocaine (2%) with or without adrenaline is generally used for anesthesia; infiltration and nerve block anesthesia are adequate in most cases. General anesthesia may be needed in patients with extensive lesions.

METHODS

Proper postoperative immobilization and care are very important to obtain satisfactory results.

Anaphylaxis is the most severe reaction of an IgE-mediated hypersensitivity. Data about affected patients may help to improve our knowledge of anaphylaxis and its medical care. We analysed data from the anaphylaxis registry of German speaking countries with regard to the provoking allergens and treatment modalities of anaphylaxis in children and adolescents. Inclusion criteria were severe systemic allergic reactions with concomitant pulmonary and/or cardiovascular symptoms. The data are collected by a password-controlled online-questionnaire. For this analysis, data of 197 reported anaphylactic reactions from children and adolescents registered between 2006 and 2009 were included. The data show that within the registered cases the most frequently affected organ systems for children and adolescents were the skin (89%) and the respiratory tract (87%) followed by symptoms of the cardiovascular system (47%) and the gastrointestinal tract (43%). The most frequent elicitors were food allergens accounting for 58% of cases, followed by insect venom (24%) and drugs (8%). The most frequent food allergens were peanuts followed by tree nuts and animal related food products. In 18% aggravating factors such as physical exercise were noted by the clinicians. 26% of the analysed patients had experienced more than one reaction. The data regarding the emergency treatment show that antihistamines (87%) and corticosteroids (85%) were often used but that adrenaline was rarely used (22% of the registered cases). Taken together these data show that the analysis of anaphylaxis by registration of affected individuals can provide data about provoking allergens and treatment measures but also suggest the impact of aggravating factors on anaphylactic reactions. The under-represented usage of adrenaline indicates the need of educational measures for patients and their physicians.

The neurotransmitters dopamine (1), L-DOPA (2), adrenaline (3), and noradrenaline (4) mediate the generation and growth of Au nanoparticles (Au-NPs). The plasmon absorbance of the Au-NPs allows the quantitative colorimetric detection of the neurotransmitters. Neurotransmitters 1, 2, and 4 are sensed with a detection limit of 2.5 x 10(-6) M, whereas the detection limit for analyzing 3 corresponds to 2 x 10(-5) M. The neurotransmitter-mediated growth of the Au-NPs is also used to probe the activity of tyrosinase. The later biocatalyst oxidizes tyrosine to L-DOPA that mediates the growth of the Au-NPs. The analysis of tyrosinase activity is important for detecting melanoma cells and Parkinson disease.

Acute bronchiolitis is the leading cause of lower respiratory tract infection and hospitalization in children less than 1 year of age worldwide. It is usually a mild disease, but some children may develop severe symptoms, requiring hospital admission and ventilatory support in the ICU. Infants with pre-existing risk factors (prematurity, bronchopulmonary dysplasia, congenital heart diseases and immunodeficiency) may be predisposed to a severe form of the disease. Clinical diagnosis of bronchiolitis is manly based on medical history and physical examination (rhinorrhea, cough, crackles, wheezing and signs of respiratory distress). Etiological diagnosis, with antigen or genome detection to identify viruses involved, may have a role in reducing hospital transmission of the infection. Criteria for hospitalization include low oxygen saturation (<90-92%), moderate-to-severe respiratory distress, dehydration and presence of apnea. Children with pre-existing risk factors should be carefully assessed.To date, there is no specific treatment for viral bronchiolitis, and the mainstay of therapy is supportive care. This consists of nasal suctioning and nebulized 3% hypertonic saline, assisted feeding and hydration, humidified O2 delivery. The possible role of any pharmacological approach is still debated, and till now there is no evidence to support the use of bronchodilators, corticosteroids, chest physiotherapy, antibiotics or antivirals. Nebulized adrenaline may be sometimes useful in the emergency room. Nebulized adrenaline can be useful in the hospital setting for treatment as needed. Lacking a specific etiological treatment, prophylaxis and prevention, especially in children at high risk of severe infection, have a fundamental role. Environmental preventive measures minimize viral transmission in hospital, in the outpatient setting and at home. Pharmacological prophylaxis with palivizumab for RSV bronchiolitis is indicated in specific categories of children at risk during the epidemic period. Viral bronchiolitis, especially in the case of severe form, may correlate with an increased incidence of recurrent wheezing in pre-schooled children and with asthma at school age.The aim of this document is to provide a multidisciplinary update on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications, identify gaps in knowledge and drive future research.

OBJECTIVE

The diagnostic and therapeutic approaches to patients with acute upper gastrointestinal bleeding have been improved during the last decades. The aim of this study was to compare the aetiology and clinical outcome of acute upper gastrointestinal bleeding (AUGIB) between two distinct periods during the last 15 years.

METHODS

The causes of AUGIB and clinical outcome of 668 patients hospitalised with the problem in 1986-1987 were compared to 636 patients with AUGIB in 2000-2001. Patients were admitted to our hospital or they bled while they were inpatients for other reasons. No patient was excluded because of age or concurrent diseases. Endoscopic haemostasis with adrenaline injection for bleeding peptic ulcers was performed in the second period while no endoscopic method of haemostasis was performed in the first period.

RESULTS

We observed an increase in the age of patients (56.5 +/- 16.9 vs 62.9 +/- 17.5 years, P < 0.0001) and the percentage of patients who received non-steroidal anti-inflammatory drugs (NSAIDs) before bleeding (from 44% to 63.5%, P < 0.0001). An increase in the diagnosis rate of gastric ulcer (12% vs 19.2%, P = 0.005) and varices (13.2% vs 3.3%, P < 0.001) with a simultaneous decrease in that of erosive gastroduodenitis (18.4% vs 7.2%, P < 0.0001) and duodenal ulcer (48.7% vs 33.3%, P < 0.0001) as a cause of bleeding was also observed. In peptic ulcer bleeding, emergency surgical haemostasis was reduced from 14% to 5.3%, P < 0.001. Overall mortality was also reduced from 5.2% to 3.1% and in peptic ulcer bleeding patients from 3.3% to 2.4%, respectively, but the differences are not statistically significant.

CONCLUSIONS

The aetiology of AUGIB has changed during the last 15 years probably due to the better therapeutic approach to chronic duodenal ulcers and increasing use of NSAIDs in the elderly. Emergency surgical haemostasis has been reduced but the reduction of mortality was not significant.