Continuous and near real-time measurements of gaseous elemental mercury (GEM) from an Unmanned Aerial Vehicle: A new approach to investigate the 3D distribution of GEM in the lower atmosphere.

We present the first real attempt to directly and continuously measure GEM through a Lumex RA-915 M, designed for real-time detection of mercury vapor, mounted on an UAV (Unmanned Aerial Vehicle, namely a heavy-lift octocopter), inside and outside the former Hg-mining area of Abbadia San Salvatore (Mt. Amiata, Italy), known as a GEM source. We tested the effectiveness of the UAV-Lumex combination at different heights in selected sites pertaining to both mining facilities and surrounding urban zones, shedding light on the GEM spatial distribution and concentration variability. The Lumex great sensitivity and the octocopter optimal versatility and maneuverability, both horizontally and vertically, allowed to depict the GEM distribution in the atmosphere up to 60 m above the ground. The acquisition system was further optimized by: i) synchronizing Lumex and UAV GPS data by means of a stand-alone GPS that was previously synchronized with Lumex; ii) using a vertical sampling tube (1.20 m high) connected to the Lumex inlet to overcome the rotors strong airflows and turbulence that would have affected GEM measurements; iii) supplying the octocopter with batteries for power supply to avoid the release of exhaust gases; iv) taking the advantage of the UAV ability to land in small spaces and stop at selected altitudes. The resulting dot-map graphical representations, providing a realistic 3D picture of GEM vertical profiling during the flights in near real-time, were useful to verify whether the guideline concentrations indicated by competent authorities were exceeded. The results showed that the GEM concentrations in the urban area, located a few hundred meters from the mining structures, and close to already reclaimed areas remained at relatively low values. Contrarily, GEM contents showed significant variations and the highest concentrations above the facilities containing the old furnaces, where increasing GEM concentrations were recorded at decreasing heights or downwind.

Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years.

Objective The aim of this study was to determine the prevalence, predictors and progression of organ damage in a monocentric cohort of systemic lupus erythematosus patients with a long follow-up. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index one year after diagnosis and every five years. Disease activity was measured by the systemic lupus erythematosus disease activity index (SLEDAI)-2K at the beginning of the follow-up. Univariate and multivariable analyses were used to detect items associated with damage. A total of 511 systemic lupus erythematosus patients (92% females, 95% Caucasian), prospectively followed from 1972 to 2014, were included. Results After a mean disease duration of 16 years (SD: 9.5) and a mean follow-up of 12.9 years (SD: 8.8), 354 patients (69.3%) had accrued some damage: 49.7% developed mild/moderate damage, while 19.5% showed severe damage. Damage was evident in 40% of 511 patients one year after diagnosis, and its prevalence linearly increased over time. Longer disease duration, higher SLEDAI, severe Raynaud's, chronic alopecia and cerebral ischaemia were significantly associated with organ damage. No associations between damage and autoantibodies, including anti-dsDNA, anti-Sm or antiphospholipid antibodies, were observed. Anyway, antiphospholipid syndrome and anticardiolipin antibodies predicted the development of neuropsychiatric damage. The ocular, musculoskeletal and neuropsychiatric systems were the most frequently damaged organs, with a linear increase during follow-up. Conclusion A high rate of moderate and severe damage has been detected early in a wide cohort of young lupus patients, with a linear trend of increase over time. Disease activity and long duration of disease predict damage, while antiphospholipid antibodies play a role in determining neuropsychiatric damage.

The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus.

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- ß2Glycoprotein I IgG/IgM >99th percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher's exact test for categorical variables and Student's t or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS.

Pregnancy in patients with autoimmune disease: A reality in 2016.

Autoimmune rheumatic diseases are chronic systemic conditions often affecting young women during their reproductive years, so that pregnancy is a major issue in their management. For a long time pregnancy has been discouraged in these women, mainly for two reasons: gestation could aggravate maternal disease and, vice versa, the disease could negatively influence the gestational outcome. The great improvement in the approach to pregnancy done in the past few decades has allowed a progressively increasing number of affected women to fulfill their family plan. Women should be informed about potential risks related to their disease, but they should also be reassured that a good pregnancy outcome is possible if conception occurs in a stable remission state, teratogenic medications have been properly withdrawn and "safe" drugs have been mantained to prevent disease flare. A brief excursus regarding the main issues regarding SLE/APS, Systemic Sclerosis and Systemic Vasculitis is provided, in the attempt to delineate the main risk factors for adverse pregnancy outcome, the onset of maternal complications and the role played by a close multi-specialistic monitoring.

The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus.

OBJECTIVES: The objective of this study was to assess the contribution of clinically significant antiphospholipid antibodies (aPL) to organ damage in systemic lupus erythematosus (SLE). METHODS: Patients with disease duration of less than 10 years and at least 5 years of follow-up were identified from two SLE registries. A clinically significant antiphospholipid antibody (aPL) profile was defined as: positive lupus anticoagulant, anticardiolipin IgG/M ≥ 40 G phospholipid units (GPL)/M phospholipid units (MPL), and/or anti-ß2-glycoprotein-I IgG/M ≥ 99th percentile on two or more occasions, at least 12 weeks apart. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Univariate and multivariate analysis compared SLE patients with and without SDI increase during a 15-year follow-up. RESULTS: Among 262 SLE patients, 33% had a clinically significant aPL profile, which was associated with an increased risk of organ damage accrual during a 5-year follow-up in univariate analysis, and during a 15-year follow-up in the multivariate analysis adjusting for age, gender, race, disease duration at registry entry, and time. In the multivariate analysis, older age at diagnosis and male gender were also associated with SDI increase at each time point. CONCLUSION: A clinically significant aPL profile is associated with an increased risk of organ damage accrual during a 15-year follow-up in SLE patients.

Social referencing and cat-human communication.

Cats' (Felis catus) communicative behaviour towards humans was explored using a social referencing paradigm in the presence of a potentially frightening object. One group of cats observed their owner delivering a positive emotional message, whereas another group received a negative emotional message. The aim was to evaluate whether cats use the emotional information provided by their owners about a novel/unfamiliar object to guide their own behaviour towards it. We assessed the presence of social referencing, in terms of referential looking towards the owner (defined as looking to the owner immediately before or after looking at the object), the behavioural regulation based on the owner's emotional (positive vs negative) message (vocal and facial), and the observational conditioning following the owner's actions towards the object. Most cats (79 %) exhibited referential looking between the owner and the object, and also to some extent changed their behaviour in line with the emotional message given by the owner. Results are discussed in relation to social referencing in other species (dogs in particular) and cats' social organization and domestication history.

Dogs' comprehension of referential emotional expressions: familiar people and familiar emotions are easier.

Dogs have been shown to discriminate between human facial expressions, and they seem to use human emotional communication to regulate their behaviour towards an external object/situation. However, it is still not clear (1) whether they just respond to the emotional message received with a corresponding increase/decrease in their level of activation or whether they perceive that the emotional message refers to a specific object, (2) which emotional message they use to modify their behaviour (i.e. whether they are following the positive message or avoiding the negative one) and (3) whether their familiarity with the informant has an effect on the dogs' behaviour. To address these issues, five groups of dogs were tested in two experiments. The first group observed the owner delivering two different emotional messages (happiness and fear) towards two identical objects hidden behind barriers, and the second group observed the owner delivering the same emotional messages but with no-objects present in the room. The third and the fourth groups observed the owner delivering a happy versus a neutral, and a negative versus a neutral emotional message towards the hidden objects. Finally, the fifth group observed a stranger acting like the owner of the first group. When the owner was acting as the informant, dogs seemed to be capable of distinguishing between a fearful and happy emotional expression and preferentially chose to investigate a box eliciting an expression of happiness rather than of fear or neutrality. Dogs, however, seemed to have greater difficulty in distinguishing between the fearful and neutral emotional messages delivered by the owner and between the happy and fearful expressions delivered by the stranger. Results suggest that dogs have learned to associate their owners' positive emotional messages to positive outcomes, and hence use their communicative messages to guide their actions. However, negative emotional messages and those delivered by strangers are not as clear to dogs.

Effects of intramural administration of Botulinum Toxin A on gastric emptying and eating capacity in obese patients.

BACKGROUND: Intraparietal gastric administration of Botulinum Toxin A has been studied in open trials to induce satiety and increase weight loss of obese patients with contradictory results. In previous studies only the antrum was the target for Botulinum Toxin A, whereas the fundus, which exerts important activity on gastric accommodation, was excluded. In this study we report the effects of injection into both gastric regions on solid gastric capacity and emptying of the stomach. MATERIALS AND METHODS: In this study we extended our previous investigations to include 30 obese patients who received Botulinum Toxin A (120 U into the antrum and 80 U into the fundus) or saline by intraparietal endoscopic injection. The two groups were homogeneous for age, gender, body weight and body mass index. Body weight and body mass index, solid gastric emptying (T(1/2) and T(lag) at the octanoic acid breath test) and maximal gastric capacity for solids (kcal) were determined before injection and 2 months later. The results were expressed as mean values (S.E.M.). t-Test or Wilcoxon test was used for statistical analysis, p<0.05 being considered significant. RESULTS: Both treatments induced a significant reduction of body weight and body mass index but Botulinum Toxin A exerted a significantly greater effect (body weight -11.8+/-0.9 kg vs. -5.5+/-1.1 kg, p<0.0002; body mass index -4.1+/-0.2 vs. -2.2+/-0.4, p<0.001). The maximal gastric capacity for solids was also reduced by both Botulinum Toxin A and placebo, the former being significantly more effective (679+/-114 kcal vs. 237+/-94 kcal, p<0.008). Botulinum Toxin A also significantly increased T(1/2) from 83.4+/-3.9 to 101.6+/-9.9 min, p<0.03) but T(lag) was unchanged. Placebo had no effect on either of these parameters. CONCLUSIONS: Our results demonstrated that Botulinum Toxin A makes weight loss easier in obese patients. It acts by increasing the solid gastric emptying time and reducing the solid eating capacity of the stomach.

COXIBs and non-selective NSAIDs in the gastroenterological setting: what should patients and physicians do?

Although adverse effects of nonsteroidal anti-inflammatory drugs occur in only a small proportion of users, the widespread use of these drugs has resulted in a substantial overall number of affected persons who experience serious gastrointestinal complications. Dyspeptic symptoms are estimated to occur in 10-60% of nonsteroidal anti-inflammatory drug users and lead to discontinuation of treatment in 5-15% of rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs. It is now well established that the point prevalence of peptic ulcer disease in patients receiving conventional nonsteroidal anti-inflammatory drug therapy ranges between 10 and 30%, representing a 10- to 30-fold increase over that found in the general population. One out of 175 users of conventional nonsteroidal anti-inflammatory drugs in the USA will be hospitalized each year for nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. The mortality of hospitalized patients remains about 5-10%, with an expected annual death rate of 0.08%. The selective COX-2 inhibitors consistently show comparable efficacy to that of conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis, but have a reduced propensity to cause gastrointestinal toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to those of combined therapy with conventional nonsteroidal anti-inflammatory drugs and gastroprotective agents. These findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain control.

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study.

OBJECTIVE: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. DESIGN: Double blind controlled study. SUBJECTS: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.1+/-4.89 kg, mean body mass index (BMI) 43.6+/-1.09 kg/m(2)) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. MEASUREMENTS: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). RESULTS: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (11+/-1.09 vs 5.7+/-1.1 kg, P<0.001) and BMI reduction (4+/-0.36 vs 2+/-0.58 kg/m(2), P<0.001) and a higher satiety score on a visual analogic scale (7.63+/-0.38 vs 4.72+/-0.44, P<0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6+/-48 vs 139+/-31, P<0.001) and a greater prolongation in gastric emptying time (+18.93+/-8 vs -2.2+/-6.9 min, P<0.05). No significant side effects or neurophysiologic changes were found. CONCLUSIONS: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

Preparation, premedication, and surveillance.

In the year since the last review, continuing pressure on endoscopy suites to improve efficiency and reduce costs without compromising patient care has led to growing interest in alternatives to pharmacological sedation and in the use of short-acting sedatives. Relaxation music, acupuncture, and the use of small-caliber endoscopes for unsedated peroral gastroscopy have therefore been suggested as ways of increasing tolerance and reducing discomfort. With regard to ultrathin and superthin endoscopes, the results are interesting, but further data from controlled trials and in studies including larger numbers of patients are still needed. The form of sedation for gastrointestinal endoscopy that has attracted greatest interest over the last year is the use by nonanesthetists of intravenous propofol, administered either alone at standard doses to achieve deep sedation, or at lower doses combined with benzodiazepines and opioids to achieve moderate sedation/analgesia. In comparison with benzodiazepines/opioids, the results were in favor of propofol: the mean time to sedation was shorter and the depth of sedation was greater. In addition, patients receiving propofol reached full recovery earlier and were discharged sooner. However, in the survey of patient satisfaction at discharge, it was found that the sedation methods did not have a significant impact on overall patient satisfaction. Some important issues concerning the narrow therapeutic range of propofol and the need for adequate training of endoscopists to deal with any problems related to deep sedation are still open - despite the growing amount of data suggesting that the drug is safe even when administered by registered nurses, an approach that is possibly more cost-effective than delivery by gastroenterologists or anesthetists. The morbidity and mortality associated with cardiopulmonary complications continue to be a significant concern during gastrointestinal endoscopy. Professional societies and national expert peer groups have issued practice guidelines for sedation and analgesia that call for continuous monitoring of the patient's hemodynamic and ventilatory status and consciousness. Direct observation is facilitated by electronic devices (pulse oximetry, capnography), directly indicating the patient's ventilatory status and the depth of sedation. Recently, it has been proposed that the bispectral index (BIS), an electroencephalography-based technique, can be used to monitor the depth of sedation during gastrointestinal endoscopy. However, the results of a recent study cast some doubt on the usefulness of the BIS, in its current version, for titrating boluses of propofol to an adequate level of sedation. Further data therefore appear to be needed to assess whether or not BIS values can help avoid unnecessary propofol dosage and can replace continuous assessment of the ventilatory effort.

Role or carbon dioxide-releasing suppositories in the treatment of chronic functional constipation: a double-blind, randomised, placebo-controlled trial.

OBJECTIVE: Treatment of chronic functional constipation is difficult. Both oral and topical laxatives may fail to adequately relieve symptoms, and there is risk of adverse effects such as functional or structural changes in the intestine, together with electrolyte disturbances. The aim of this study was to evaluate the efficacy and safety of a suppository that combines sodium bicarbonate and potassium bitartrate in a polyethylene glycol base to generate approximately 175mL of carbon dioxide (CO(2)). This release distends the rectal ampulla, thereby stimulating peristalsis and a subsequent bowel movement. PATIENTS AND METHODS: This was a prospective, crossover, double-blind, randomised, placebo-controlled, sequential study of outpatients with chronic functional constipation. Each patient received two suppositories of identical appearance, containing active drug or placebo. The sequence of active drug-placebo (sequence 1) or placebo-active drug (sequence 2) was randomised in groups of eight. The second suppository was taken 7 days after the first. The following parameters were evaluated and scored: evacuation time, type of evacuation, feeling of emptying of the rectal ampulla, stool characteristics, anal complaints, abdominal pain and overall patient assessment. RESULTS: A total of 29 patients entered the study. According to a restricted sequential plan, a statistical significance (p < 0.05) in favour of the active drug was reached after 26 patients. A positive response within 30 minutes of introduction of the suppository occurred in 51.7% and 6.9% of patients treated with the active drug and placebo, respectively (p = 0.0003). Normal evacuation occurred in 65.5% and 24.1% of patients treated with the active drug and placebo, respectively (p = 0.004). Normal stool consistency was found in 44.8% and 7.2% of patients treated with the active drug and placebo, respectively (p = 0.04). Patient assessment of treatment as satisfactory occurred in 51.7% and 20.7% of subjects treated with the active drug and placebo, respectively (p = 0.029). Only a trend in favour of the active drug was observed with regard to feeling of incomplete evacuation, and active drug was comparable to placebo with regard to anal and abdominal tolerability CONCLUSION: The CO(2)-releasing suppository may represent an alternative to rectal laxatives for the relief of chronic functional constipation. The data obtained in this study indicate that CO(2)-releasing suppositories may be usefully and safely employed in the treatment of patients at risk for electrolyte disorders such as the elderly or patients with renal or cardiovascular disorders.

Gastrointestinal side-effects of traditional non-steroidal anti-inflammatory drugs and new formulations.

Although adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) occur in only a small proportion of users, the widespread use of these drugs has resulted in a substantial overall number of affected persons who experience serious gastrointestinal complications. Dyspeptic symptoms are estimated to occur in 10-60% of NSAID users and lead to discontinuation of treatment in 5-15% of rheumatoid arthritis patients taking NSAIDs. It is now well established that the point prevalence of peptic ulcer disease in patients receiving conventional NSAID therapy ranges between 10 and 30%, representing a 10-30-fold increase over that found in the general population. One of 175 users of conventional NSAIDs in the USA will be hospitalized each year for NSAID-induced gastrointestinal damage. The mortality of hospitalized patients remains about 5-10%, with an expected annual death rate of 0.08%. The selective COX-II inhibitors (rofecoxib, celecoxib, parecoxib, etoricoxib, valdecoxib, lumiracoxib) show consistently comparable efficacy to that of conventional non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis and osteoarthritis, but have a significantly reduced propensity to cause gastrointestinal toxicity. In many cases, the gastric effects of therapeutically active doses of COX-II inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. These findings warrant the consideration of COX-II inhibitors as first-line therapy in patients requiring long-term pain control.

Preparation, premedication and surveillance.

The main end points for sedation during endoscopy are patients' satisfaction, short duration of the procedure, and safety. During the last year, attention has focused on attempting to identify the "ideal" candidate for moderate sedation/analgesia and on the importance of providing the patient with appropriate information before the procedure. The increasing pressure to perform more procedures, reduce costs, and achieve shorter patient turnaround times has affected recent approaches to sedation during endoscopy, focusing attention on alternatives to pharmacological sedation such as providing relaxing music, using small-caliber endoscopes for unsedated peroral gastroscopy, and using magnetic endoscopic imaging to increase tolerance and reduce discomfort during colonoscopy. The results, however, have not been convincing. The role of benzodiazepines was discussed in some studies, highlighting the well-known effect of midazolam on postprocedural amnesia, its pharmacological profile and tolerability after intranasal spraying in healthy volunteers, and the efficacy and safety of this route of administration as an alternative to intravenous administration in diagnostic upper gastrointestinal endoscopy. The form of sedation for gastrointestinal endoscopy that has attracted great interest over the last year is the use of intravenous propofol, either alone or with concomitant benzodiazepines or opioids. As expected in view of the drug's known pharmacological properties, the quality of sedation was better and recovery time was shorter in patients treated with propofol. However, important questions involving the narrow therapeutic range and the mode of administration of propofol (by endoscopists or nurses, or by anesthesiologists) remain open. One important aspect of sedation procedures is prevention of cardiopulmonary complications. The use of electronic monitoring techniques, with a pulse oximeter, has been recommended as a standard procedure during digestive endoscopy; however, pulse oximetry no longer reflects the normal ventilatory functions and does not detect episodes of severe CO2 retention. CO2 monitoring by transcutaneous measurement - or better, by capnography - appears to be useful, as an alternative to pulse oximetry, as a measure of hypoventilation, and for detecting potentially important abnormalities in respiratory activity in patients undergoing sedation for gastrointestinal endoscopy. With regard to preparation for endoscopic procedures, several "ideal" formulas for bowel preparation have been presented. These include the use of sodium phosphate compounds as an alternative to polyethylene glycol electrolyte lavage solutions (PEG-ELS); however, the results so far have been conflicting. The best and most cost-effective bowel cleansing procedure for colonoscopy and sigmoidoscopy has yet to be established.

Upper GI bleeding in healthy full-term infants: a case-control study.

OBJECTIVE: The aim of this case-control study was to evaluate the frequency and the type of mucosal lesions in newborn babies with upper GI bleeding (UGIB), the diagnostic role and safety of upper GI endoscopy, and the recognition of risk factors associated with the hemorrhagic event. METHODS: A population of 5180 infants born from June, 1988 to May, 1997 was examined. A case was defined as any patient who had UGIB within 4 days of delivery. The diagnosis was made by endoscopic examination in an endoscopy room. The following parameters were determined: amniotic fluid features, funicular blood pH, Apgar index at 5 min, neonatal weight, body length, gestational age, and the presence of other pathologies. Biochemical profiles were also evaluated. Clinical and demographic data of the mothers of the newborn babies were analyzed. Sera of cases and the respective parents were tested for gastrin and pepsinogen. As a control group, 53 full-term healthy infants matched for sex and age were randomly selected from the population of infants born in our pediatric department. RESULTS: Sixty-four of 5180 newborn babies (1.23%) suffered from UGIB within 26.5 +/- 20 h of life. In 53 of 64 cases (mean age = 24.2 +/- 25.5 h) it was possible to carry out an endoscopic examination. In one case, endoscopy was limited to the esophagus because of the presence of multiple mucosal ulcers and substenosis of the viscus. Esophageal damage was observed in 24/53 patients. The esophageal lesions were isolated in nine cases, and occurred jointly with gastric or duodenal damage in 14 cases and one, respectively. Gastric and duodenal lesions were seen in 43/52 and 1/52 patients, respectively. There were 17 cases of gastric ulcers and one case of duodenal ulcer. Blood clots were observed in 14 gastric ulcer patients; in one case there was evidence of active bleeding at the margins of a gastric ulcer. There was no significant difference with regard to the demographic and clinical characteristics of the cases and controls. Median values of serum gastrin of the cases and controls were similar. Median serum pepsinogen was significantly higher in the case group. CONCLUSIONS: UGIB in the newborn babies is often associated with clinically relevant mucosal lesions of the upper GI tract. The evolution, after treatment with antisecretory drugs, is generally rapid and favorable, with clinical recovery usually obtained within 24-48 h. The higher serum pepsinogen levels may only represent a significant risk factor of mucosal lesions and complications.

Review article: Helicobacter pylori and NSAID gastropathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are known to share a number of pathogenic mechanisms, but there is no evidence to show a significant synergic action between the two risk factors. Studies assessing this subject have differed in almost every aspect of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use. They also differed in their end-points, the definition of dyspepsia and the regimes used for eradication of H. pylori. However, some conclusions may be drawn from the results of clinical trials. In H. pylori-positive patients without mucosal lesions, NSAIDs may aggravate dyspeptic symptoms but, with the exception of elderly patients, they do not present a definite major risk of gastric and duodenal lesions and, above all, of ulcer-correlated complications. So what recommendations can be made with regard to H. pylori eradication in patients requiring treatment with NSAIDs? The microorganism and the anti-inflammatory drugs are undoubtedly independent causes of gastric and duodenal damage. Patients taking NSAIDs who are found to have gastric or duodenal ulcers should therefore be tested for the bacterium and specifically treated, since H. pylori and NSAID-induced ulcers may be macroscopically indistinguishable. Whether asymptomatic patients taking NSAIDs should be tested and treated for H. pylori infection is still a matter of debate.

The effects on gastroduodenal mucosa of a new nonsteroidal anti-inflammatory drug, amtolmetin-guacyl, versus piroxicam in healthy volunteers: a short-term, double-blind, endoscopically controlled study.

AIM: Amtolmetin-guacyl (AMG) (2-[2[1-methyl-5-(4-methylbenzoyl) pyrrol-2-yl] acetamido] acetic acid 2-methoxyphenyl ester) is a recent drug that, in preliminary studies, has shown effective anti-inflammatory properties with improved gastrointestinal safety. Our study was designed to investigate the effects of AMG and piroxicam on gastroduodenal mucosa in healthy volunteers. MATERIALS AND METHODS: Forty-two healthy volunteers aged 18--45 years were randomized in a double-blind manner to AMG 1200 mg for 2 days and 600 mg for 12 days, or piroxicam 40 mg for 2 days and 20 mg for 12 days. Endoscopic evaluation and laboratory tests were performed at baseline and at the end of the treatment. The mucosa was evaluated by endoscopy using a predefined scale: the score could range from 0 to 4. Only volunteers with endoscopy grade 0-1 entered the trial. RESULTS: The median post-treatment endoscopy gastric injury scores were 1 (range 0--4) in the AMG-treated volunteers and 3 (range 0--4) in the piroxicam-treated volunteers (P = 0.04). There were two cases with an endoscopic gastric score of 4 in the AMG group, and seven in the piroxicam group (P = 0.1). The corresponding values in the duodenum were 1/21 volunteers in the AMG group and 1/21 in the piroxicam group. Eight out of 11 subjects with an endoscopic score of 4 were Helicobacter pylori negative, and 3/11 were infected by the micro-organism. Different adverse reactions were reported by 15/21 volunteers (71%) in the AMG group and by 12/21 (57%) in the piroxicam group. None of these events resulted in interruption of the study. CONCLUSIONS: AMG is a new anti-inflammatory drug with limited gastric toxicity. If these findings are confirmed on a wider scale in long-term trials, then the drug might become a valid alternative to current treatments, especially for patients such as those with rheumatoid arthritis who need steroids and second-line drugs simultaneously.

Preparation, premedication, and surveillance.

The endoscopic literature published during the past year has once again confirmed that there is significant variation from country to country regarding whether or not patients wish to receive conscious sedation during endoscopy (and particularly colonoscopy) - and there may even be variation from one endoscopic unit to another within the same country. Particular attention has been given to attempts to identify "ideal" candidates for conscious sedation, and to the importance of providing patients with information before the procedure. It has been shown that patients who receive detailed information about a medical procedure beforehand are able to benefit from this. The role of benzodiazepines, particularly midazolam, was investigated in studies emphasizing that the dosage should be kept to the minimum that is compatible with patient comfort and successful performance of the procedure. There have been few publications comparing propofol with midazolam. As expected, in view of the known pharmacological properties of the two drugs, the quality of sedation was better and the recovery time was shorter in patients who were treated with propofol. However, important questions are still open regarding the narrow therapeutic range of propofol and the methods by which it is administered (by endoscopists or by anesthesiologists). An important aspect of sedation procedures is the prevention of hypoxia and cardiopulmonary complications. Recent endoscopic reports have added little further information concerning the well-known risk of oxygen desaturation during conscious sedation. Performing endoscopy in unsedated patients reduces, but does not eliminate, the risk of hypoxia. Among the various risk factors, it has been found that chronic respiratory failure and coronary heart disease are factors predictive of severe desaturation and relevant electrocardiographic changes. The use of electronic monitoring techniques with pulse oximetry is recommended as a standard procedure during digestive endoscopy; however, it has been observed that when supplemental oxygen is administered, pulse oximetry no longer reflects normal ventilatory function and does not detect episodes of severe CO2 retention. Transcutaneous measurement of PCO2 therefore seems more reliable as a means of assessing hypoventilation. Several papers have proposed "ideal formulas" for bowel preparation for endoscopic procedures. Various regimens have been proposed as alternatives to polyethylene glycol electrolyte lavage solution (PEG-ELS) and sodium phosphate compounds, with different results. On the whole, there is still little information regarding the best and most cost-effective method of bowel cleansing for colonoscopy and flexible sigmoidoscopy.

Nonsteroidal anti-inflammatory drug gastropathy and Helicobacter pylori: the search for an improbable consensus.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are known to share a number of pathogenic mechanisms, but there is no evidence to show a significant synergistic action between these two risk factors. Studies to assess possible interactions in the pathogenesis of dyspepsia and upper gastrointestinal mucosal lesions have differed in their endpoints, the definition of dyspepsia, and the regimens used for eradication of H. pylori. However, some conclusions may be drawn from the results of clinical trials. As far as dyspepsia is concerned, an association between NSAID dyspepsia and infection with H. pylori, seems likely, but it is difficult to make sense of the discrepant data that are currently available. On the contrary, neither short- nor long-term NSAID administration presents a definite major risk of gastric and duodenal injury or, above all, of ulcer-related complications (bleeding or perforation) in H. pylori-positive patients. Based on these considerations, what recommendations can be made with regard to H. pylori eradication in patients requiring treatment with NSAIDs? H. pylori and anti-inflammatory drugs are probably independent causes of gastric and duodenal damage. Patients taking NSAIDs who are found to have gastric or duodenal ulcers should, therefore, be tested for the bacterium and specifically treated, because H. pylori and NSAID-induced ulcers may be macroscopically indistinguishable. Whether asymptomatic patients taking NSAIDs should be tested and treated for H. pylori infection is still a matter of debate.

Prophylaxis and treatment of non-steroidal anti-inflammatory drug-induced upper gastrointestinal side-effects.

The use of specific agents to heal mucosal lesions or to prevent non-steroidal anti-inflammatory drug toxicity, has focused upon two approaches: replacement of prostaglandin deficiency and inhibition of acid secretion. Acid suppression with traditional ulcer healing doses of H2-blockers is effective in healing gastric and duodenal ulcers upon discontinuation of the offending drug. In the event the non-steroidal anti-inflammatory drug must be continued, the use of H2-blockers is associated with a decrease in the healing rate. In long-term prevention studies, H2-blockers significantly reduce duodenal ulcer rates, but are ineffective in reducing gastric ulceration. More potent acid inhibition with a double-dose of H2-blockers (famotidine 80 mg daily, ranitidine 600 mg daily) may reduce the risk of gastric and duodenal ulcers. Marked acid suppression with proton pump inhibitors (omeprazole 20-40 mg, lansoprazole 30 mg daily) also appears to be very effective in healing gastric and duodenal ulcers in patients continuing the offending drug as well. An analysis of pooled data from comparative studies on omeprazole vs ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of the proton pump inhibitor, ranging from 10 to 40%. In long-term prevention studies, omeprazole (20 mg daily) and pantoprazole (40 mg daily) have also been shown to reduce the risk of gastric and duodenal ulcers and non-steroidal anti-inflammatory drug-related dyspepsia. Current data from recent comparative studies of omeprazole (20 mg daily) vs ranitidine (150 mg daily) and misoprostol (200 microg daily) showed that, after 6 months' follow-up, the proton pump inhibitor was significantly superior to control drugs in reducing the risk both of gastric and duodenal ulcer. Misoprostol (at doses ranging from 400 microg to 800 microg/day) is an effective form of therapy for preventing non-steroidal anti-inflammatory drug-induced gastroduodenal lesions. However high-dose misoprostol only, seems adequate for the prevention of ulcer complications, mainly in high-risk non-steroidal anti-inflammatory drug users. Thus, available data are undoubtedly in favour of the proton pump inhibitors as well tolerated and effective drugs in the prophylaxis and treatment of non-steroidal anti-inflammatory drug-related mucosal lesions in the gastrointestinal tract.