[Laparoscopic surgery of perforated duodenal ulcer]. / Trattamento laparoscopico dell'ulcera duodenale perforata.

BACKGROUND AND AIM: Endoscopic diagnostic and therapeutic possibilities have been increased by videolaparoscopy. The method enables an immediate reliable diagnosis to be made, associated with possible surgical treatment. METHODS: The authors report their laparoscopic experience relating to the treatment of perforated duodenal ulcer from 1972 to 1995 in 8 patients divided into two groups. Jacob Palmer's laparoscopic operator was used in the first group together with Menghini's needle for the aspiration of peritoneal effusion; the operation was performed under local anesthesia with nitrogen monoxide insufflation using Taylor's technique number I. The second group underwent ulcorrhaphy with omentopexy, again using a laparoscopic route, together with abundant lavage and accurate aspiration of fibrin. RESULTS: The patients in the first group made a prompt recovery in terms of their general conditions following the remission of fever, pain, diminished leukocytes and an early renewal of canalisation; cicatrisation of the ulcer was confirmed by the endoscopic control on day 15. Patients in the second group showed early deambulation approximately 4 hours after surgery; canalisation occurred after about 6 hours and all patients were discharged on day 3. The eradication of Helicobacter pylori led to complete resolution, as was confirmed by subsequent follow-ups. CONCLUSIONS: Laparoscopy was found to be extremely useful both in the immediate diagnosis of acute abdomen following perforated ulcer and in its surgical treatment as a result of the introduction of operating laparoscopes and in particular videolaparoscopes, together with surgical instruments that allow careful abdominal cleansing and ulcorrhaphy. In the authors' opinion, the latter procedure is the most suitable for managing this pathology.

[Cholecystic-choledochal calculi. Endolaparoscopic treatment]. / Calcolosi colecisto-coledocica. Trattamento endolaparoscopico.

BACKGROUND AND AIM: Common bile duct calculosis is a pathology which has always been treated using traditional laparotomic surgery. The introduction of endoscopic papillosphincterotomy and mini-invasive and videolaparoscopic methods has drawn attention to the fact that these methods may be able to replace conventional surgery. METHODS: The authors examine the epidemiological and clinical aspects of common bile duct calculosis, reporting their experience in ten female patients treated during the period from 1992 to 1997, all of whom presented jaundice, pain and fever. Of these, eight underwent papillosphincterotomy using an endoscopic approach, followed by laparoscopic removal of common bile duct calculi within 24 hours. In two cases it was necessary to resort to conventional methods owing to difficulty in cannulating the papilla caused by a diverticulum in one patient and stenosis in the other, and the tenacious synechiae between the common bile duct and the gallbladder. RESULTS: The postoperative period was free of complications. CONCLUSIONS: The associated treatment, namely endoscopic papillosphincterotomy and endoscopic cholecystectomy proved a valid alternative to traditional laparotomic treatment, demonstrating a good level of reliability and safety for patients and reductions in terms of resources and hospitalisation time.

[Ogilvie's syndrome]. / La sindrome di Ogilvie.

"Ogilvie's syndrome" or the idiopathic dilatation of the colon is an infrequent pathology whose underlying physiopathology is not yet well known. On the basis of their experience and having reviewed the literature, the authors affirm that this syndrome is caused by the inhibition of gastrointestinal hormones which, under the control of the neurohypophysis, contribute to colon motility. This supposition is backed up by the fact that medical treatment with somatostatin or octreotide leads to the resolution of the disorder.

Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma.

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.

Negative/low expression of the Met/hepatocyte growth factor receptor identifies papillary thyroid carcinomas with high risk of distant metastases.

To investigate the clinical impact of Met/hepatocyte growth factor receptor (HGF-R) expression in thyroid cancer we studied 163 thyroid carcinomas (129 papillary, 21 follicular, and 13 anaplastic) from patients followed-up for 25-147 months postthyroidectomy. Forty-nine thyroid adenomas were also studied. Met/HGF-R expression was evaluated by semiquantitative immunohistochemistry, measuring both the proportion (scale of 0-5) and the intensity (scale, 0-5) of stained cells and calculating a total score (scale of 0-10). Met/HGF-R was absent in the normal thyroid tissue, absent or focally expressed in follicular and anaplastic tumors, and expressed at various levels in most papillary carcinomas, including microcarcinomas. Papillary carcinomas were thus categorized as having negative/low Met/HGF-R (n = 50; total score, < or = 5) or high Met/HGF-R expression (n = 70; total score, > 5). High Met/HGF-R was inversely associated with vascular invasion (P = 0.0308), but not with other prognostic factors. Negative/low Met/HGF-R expression was the most effective predictor by multivariate Cox analysis of distant metastases (hazard ratio = 9.71; P = 0.0036), higher than extrathyroid invasion (hazard ratio = 4.25; P = 0.0181), age (< or = 45 vs. > 45 yr; hazard ratio = 3.99; P = 0.0099), and vascular invasion (hazard ratio = 3.19; P = 0.0358). These findings suggest a role for Met/HGF-R in papillary thyroid cancer and its clinical use to select patients with a high risk of distant metastases.

In situ evidence of neoplastic cell phagocytosis by macrophages in papillary thyroid cancer.

We evaluated the occurrence, tissue distribution, and prognostic value of tumor-associated macrophages in 121 papillary thyroid carcinomas using immunohistochemical staining with anti-CD68 antibody in archival paraffin-embedded sections. Lymphocytic infiltration and dendritic cell presence were also evaluated. Three groups were identified according to the presence and characteristics of macrophages: 1) tumors without evidence of infiltrating macrophages: (n = 35); 2) tumors with infiltrating macrophages but no evidence of neoplastic cells phagocytosis (n = 68); and 3) tumors with infiltrating macrophages and in situ evidence of active neoplastic cell phagocytosis (n = 18). Neoplastic cell phagocytosis by macrophages was positively correlated with both lymphocytic infiltration and dendritic cells (P = 0.0000), whereas it was negatively correlated with vascular invasion (P = 0.0032). Distant metastases developed in none of the 18 tumors with neoplastic cell phagocytosis, but occurred in 15 of 103 of the remaining tumors (P = 0.0647) and were significantly and negatively associated with lymphocytic infiltration or dendritic cells. The present study indicates, therefore, that immune reaction, involving neoplastic cell phagocytosis by macrophages and lymphocytic infiltration, plays a role in the development of distant metastases in patients with papillary thyroid cancer.

Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins.

When administered by inhalation, bradykinin provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve activation of sensory nerve endings. However, little is known of the change in airway responsiveness to bradykinin after cyclo-oxygenase blockade. The aim of the present study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation, on bradykinin-induced bronchoconstriction in a group of 12 asthmatic subjects. The subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg x mL(-1)) or matched placebo (glycine, solution of 30 mg x mL(-1)) 15 min prior to bronchoprovocation tests with bradykinin and methacholine in a randomized, double-blind order with at least a 5 day interval. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1), and responsiveness to agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration both of L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, with gradual recovery within 20 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to bradykinin in 11 of the 12 subjects studied, the geometric mean (range) values for PC20 bradykinin increasing significantly (p<0.001) by 1.7 doubling dose from 0.55 (0.11-5.05) to 1.72 (0.26-6.05) mg x mL(-1) after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. It is concluded that administration of lysine acetylsalicylate by inhalation protects the asthmatic airways against bradykinin-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the bronchoconstriction to kinins in human asthma.

Time course of changes in adenosine 5'-monophosphate airway responsiveness with inhaled heparin in allergic asthma.

BACKGROUND: Recent studies have shown that inhaled heparin exerts a protective effect against various bronchoconstrictor stimuli in asthma, possible through an inhibition of mast cell activation. OBJECTIVE: Because adenosine 5'-monophosphate (AMP) elicits bronchoconstriction by augmenting mast cell mediator release, we have investigated the effect of inhaled heparin (15,000 units USP/ml, 4 ml) on the bronchoconstrictor response to this agonist and to methacholine in a randomized, double-blind, placebo-controlled study of 10 subjects with asthma. We also carried out a separate randomized, double-blind study in seven additional volunteers with asthma to examine in more detail the time-course of change in bronchial reactivity to inhaled AMP after treatment with nebulized heparin. RESULTS: Inhaled heparin significantly increased the provocative concentration of AMP causing a 20% decrease in forced expiratory volume in 1 second (PC20 FEV1-AMP) from the postplacebo treatment value of 22.3 mg/ml (range, 5.7 to 68.9 mg/ml) to 48.1 mg/ml (range, 5.1-196.8 mg/ml) (p < 0.01). When compared with placebo, inhaled heparin failed to alter the airway responsiveness to methacholine; the mean (range) PC20 methacholine values were 1.00 mg/ml (0.44 to 4.76 mg/ml) and 1.08 mg/ml (0.46 to 5.08 mg/ml), respectively. After placebo administration, the PC20 AMP values at 15, 60, and 180 minutes did not differ significantly from each other; their geometric mean (range) values were 26.1 mg/ml (5.9 to 85.8 mg/ml), 26.6 mg/ml (6.3 to 87.8 mg/ml), and 24.9 mg/ml (5.2 to 80.2 mg/ml), respectively. When compared with placebo, the PC20 values for AMP after administration of inhaled heparin were significantly increased up to 57.3 mg/ml (14.7 to 176.0 mg/ml) and to 52.7 mg/ml (13.9 to 90.8 mg/ml) at 15 minutes and 60 minutes, respectively. At 180 minutes, inhaled heparin failed to affect AMP airway responsiveness; the PC20 AMP was not significantly different from that of placebo, with a value of 30.6 mg/ml (4.8 to 93.3 mg/ml). CONCLUSION: Heparin administered by inhalation is effective in attenuating the airway response to AMP but not to methacholine. The time course of change in bronchial reactivity to AMP has a peak effect at 15 minutes and lasts up to 60 minutes. It is possible that the mechanism(s) underlying the protective effects of inhaled heparin in asthma may be related to an inhibitory modulation of mast cell activation.

Neutral endopeptidase inhibition with inhaled phosphoramidon: no effect on bronchial responsiveness to adenosine 5'-monophosphate (AMP) in asthma.

Part of the contractile response of adenosine in the asthmatic airways may be due to the activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides. At present, little is known about the potential role of lung peptidases in modulating adenosine-induced airway dysfunction in humans in vivo. We have, therefore, investigated the change in bronchial reactivity to adenosine 5'-monophosphate (AMP), after treatment with inhaled phosphoramidon, a potent neutral endopeptidase (NEP) inhibitor, in a double-blind, placebo-controlled, randomized study of 12 asthmatic subjects. Subjects attended on six separate occasions, during which concentration response studies with inhaled AMP and methacholine were carried out, initially in the absence of treatment and then after nebulized phosphoramidon sodium salt (10[-5] M) or matched placebo 5 min prior to a bronchoprovocation test with AMP or methacholine. Agonist responsiveness was expressed as the provocative concentration of AMP or methacholine producing a 20% fall in FEV1 from baseline (PC[20,AMP] or PC[20,meth], respectively). When compared to placebo, phosphoramidon failed to potentiate the airway response to AMP. The geometric mean (range) PC20 AMP value of 23.4 (4.4-190.6) mg x mL(-1) after placebo was not significantly different from that of 20.7 (45-100.9) mg x mL(-1) obtained after phosphoramidon. The lack of change in bronchial reactivity to adenosine 5'-monophosphate after phosphoramidon indicates that endogenous airway neutral endopeptidase may not be of physiological importance in modulating the contractile response of adenosine in the airways. Thus, the present data do not support the view that activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides is important in the airway response to adenosine

Inhaled lysine acetylsalicylate (L-ASA) attenuates the bronchoconstrictor response to adenosine 5'-monophosphate (AMP) in asthmatic subjects.

When administered by inhalation, adenosine 5'-monophosphate (AMP) provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve mast cell mediator release. However, little is known of the change in airway responsiveness to AMP after cyclo-oxygenase blockade. The aim of this study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on AMP-induced bronchoconstriction in a group of nine asthmatic subjects. The subjects studied attended the laboratory on six separate occasions to receive nebulized L-ASA (solution of 90 mg.ml-1) or matched placebo (glycine solution, 30 mg.ml-1) 15 min prior to bronchoprovocation tests with AMP, histamine and methacholine in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to AMP in all the subjects studied, the geometric mean (range) values for PC20 AMP increasing significantly from 36.3 (7.9-250.5) to 101.8 (27.2-1300) mg.ml-1 after placebo and L-ASA, respectively. Moreover, nebulized L-ASA induced a small but significant reduction in airway responsiveness to histamine, the geometric mean (range) PC20 values for histamine increasing from 2.77 (1.05-5.49) to 4.36 (1.69-11.24) mg.ml-1 after placebo and L-ASA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of an inhaled neutral endopeptidase inhibitor, phosphoramidon, on baseline airway calibre and bronchial responsiveness to bradykinin in asthma.

BACKGROUND: Bradykinin is a potent vasoactive peptide which has been proposed as an important inflammatory mediator in asthma since it provokes potent bronchoconstriction in asthmatic subjects. Little is known at present about the potential role of lung peptidases in modulating bradykinin-induced airway dysfunction in vivo in man. The change in bronchial reactivity to bradykinin was therefore investigated after treatment with inhaled phosphoramidon, a potent neutral endopeptidase (NEP) inhibitor, in a double blind, placebo controlled, randomised study of 10 asthmatic subjects. METHODS: Subjects attended on six separate occasions at the same time of day during which concentration-response studies with inhaled bradykinin and histamine were carried out, without treatment and after each test drug. Subjects received nebulised phosphoramidon sodium salt (10(-5) M, 3 ml) or matched placebo for 5-7 minutes using an Inspiron Mini-neb nebuliser 5 minutes before the bronchoprovocation test with bradykinin or histamine. Agonists were administered in increasing concentrations as an aerosol generated from a starting volume of 3 ml in a nebuliser driven by compressed air at 8 1/min. Changes in airway calibre were measured as forced expiratory volume in one second (FEV1) and responsiveness as the provocative concentration causing a 20% fall in FEV1 (PC20). RESULTS: Phosphoramidon administration caused a transient fall in FEV1 from baseline, FEV1 values decreasing 6.3% and 5.3% on the bradykinin and histamine study days, respectively. When compared with placebo, phosphoramidon elicited a small enhancement of the airways response to bradykinin, the geometric mean PC20 value (range) decreasing from 0.281 (0.015-5.575) to 0.136 (0.006-2.061) mg/ml. In contrast, NEP blockade failed to alter the airways response to a subsequent inhalation with histamine, the geometric mean (range) PC20 histamine value of 1.65 (0.17-10.52) mg/ml after placebo being no different from that of 1.58 (0.09-15.21) mg/ml obtained after phosphoramidon. CONCLUSIONS: The small increase in bronchial reactivity to bradykinin after phosphoramidon exposure suggests that endogenous airway NEP may play a modulatory role in the airways response to inflammatory peptides in human asthma.

Cross-tachyphylactic airway response to inhaled bradykinin, kallidin and [desArg9]-bradykinin in asthmatic subjects.

Kinins are oligopeptides that may act as mediators in the pathogenesis of bronchial asthma by interacting with specific cell surface receptors designated B1 and B2. When administered by inhalation to asthmatic subjects, bradykinin and kallidin, but not [desArg9]-bradykinin, provoke potent bronchoconstriction, thus suggesting a specific effect compatible with the stimulation of B2 receptors. To characterize further the receptor(s) mediating this bronchospastic response we have carried out cross-tachyphylactic studies with inhaled bradykinin, kallidin, and [desArg9]-bradykinin, administered in a randomized double-blind fashion in a group of 10 asthmatic subjects. Inhalation of bradykinin and kallidin, but not [desArg9]-bradykinin, elicited concentration-related falls in forced expiratory volume in one second (FEV1) in all the subjects studied. The geometric mean provocation concentrations of inhaled agonists reducing FEV1 by 20% of baseline (PC20) were 0.12 and 0.28 mg.ml-1 for bradykinin and kallidin, respectively. When inhaled at concentrations up to 10.62 mg.ml-1, [desArg9]-bradykinin failed to provoke any significant fall in FEV1 from baseline in any of the subjects studied. Following recovery from the second bradykinin challenge, provocation with kallidin revealed a reduced response to this agonist, the PC20 value increasing from 0.28 to 1.23 mg.ml-1. Similarly, once the airways had recovered from the second kallidin challenge, provocation with bradykinin also showed a reduced response, the PC20Bk increasing from 0.12 to 0.94 mg.ml-1. Surprisingly, despite failing to cause bronchoconstriction, repeated exposures with inhaled [desArg9]-bradykinin reduced the airway response to bradykinin, the PC20Bk increasing from 0.12 to 0.41 mg.ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

[Basal lipid energy utilization in obese women and men]. / Utilizzazione energetica basale di lipidi in donne e uomini obesi.

In 16 abdominal type obese males, in 16 gluteal-femoral type obese females and in 10 nonobese males and 9 nonobese females, as controls, the influence of body fat distribution on basal lipid oxidation was evaluated by indirect calorimetry. Basal lipid oxidation was significantly higher in the obese males (1.21 +/- 0.12 g/kg-FFM.die) than in the nonobese males (0.47 +/- 0.13 g/kg-FFM.die; p less than 0.001), but not significantly different between obese and nonobese females (0.98 +/- 0.16 and 0.89 +/- 0.13 g/kg-FFM.die; p ns). A significant correlation between basal lipid oxidation and percentage of body fat was found only in the male subjects (r = 0.51; p less than 0.01). These results suggest that basal lipid oxidation differs in the two sexes according to adipose tissue anatomic location.

Blood rheology changes during bezafibrate treatment.

To evaluate the effect of bezafibrate on the haemorheological pattern, 30 atherosclerotic non-diabetic patients were enlisted in a double-blind, comparative, parallel group trial with bezafibrate (600 mg daily) or placebo being randomly assigned. The 45-day treatment period was preceded by a three week pharmacological wash-out. Haemorheological parameters such as whole-blood, plasma and serum viscosity, haematocrit, fibrinogen, fibrinogen/albumin ratio and erythrocyte filterability were evaluated before and at the end of treatment. The results showed no change in haemorheological determinants in the placebo-treated group but a significant reduction in whole-blood viscosity, in haematocrit, in fibrinogen and fibrinogen/albumin ratio was observed in the bezafibrate treated patients. No variation was present in the plasma and serum viscosity and in the erythrocyte filterability.