Biomedical subjects
Publications and source records attributed to G Ferla.
We present the case of a 44-year old man, presenting with acute left flank pain and gross haematuria, affected by bilateral renal mass and massive para-aortic and mediastinic lymphadenopathy, highly suspicious for metastatic renal cancer.
BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). METHODS: The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. RESULTS: Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. CONCLUSIONS: Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.
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BACKGROUND & AIMS: The notion that specific receptors account for the ability of natural and synthetic cannabinoids to alter physiological functions, prompted this study aimed at assessing their functional presence in the human gut. METHODS: The effects have been studied of cannabinoids and selective antagonists of their receptors on chemically or electrically evoked contractions in preparations of human intestinal smooth muscle in vitro. RESULTS: Atropine prevented the contractions of longitudinal and circular muscle strips of ileum and colon induced by carbachol or electrical field stimulation; tetrodotoxin abolished only the latter which suggests they do involve activation of cholinergic neurons. The synthetic cannabinoid (+)WIN 55,212-2 had no effect on carbachol contractions, but in a concentration-dependent fashion prevented those elicited by electrical field stimulation - which were insensitive to the putative endogenous cannabinoid anandamide - more potently in longitudinal than in circular strips. The selective CB1 receptor antagonist SR141716, which had no effect in the absence of (+)WIN 55,212-2, competitively antagonised its inhibition of electrical field stimulation contractions, unlike the selective CB2 antagonist SR144528. CONCLUSIONS: Cannabinoid CB1 receptors are functionally present in the human ileum and colon; their pharmacological activation apparently results in inhibition of excitatory cholinergic pathways subserving smooth muscle contraction.
BACKGROUND: There are now a variety of methods to assess body fat distribution, anthropometric (waist circumference and waist/hip W/H ratio), computed tomography (CT), and ultrasound (US) measurements, with CT considered as the reference method. Bariatric surgery leads to a significant and usually durable weight loss in morbidly obese patients; when assessing its results, it is of interest to measure changes of total fat tissue and of body fat distribution. METHODS: In this study, we compared anthropometric, US, and CT measurements of body fat distribution under basal conditions and 1 year after laparoscopic adjustable gastric banding (LAGB); 120 morbidly obese patients were considered at baseline, and 40 patients were re-evaluated 1 year after LAGB. RESULTS: Thickness of visceral and subcutaneous fat measured through CT and US methods was superimposable both under basal conditions and 1 year after LAGB, and the highest correlation was found between CT and US data on visceral fat, followed by CT and US data on subcutaneous fat; a fair correlation was also found between CT and US data on visceral fat and waist circumference. CONCLUSION: We suggest that evaluation of body fat distribution is accomplished by US instead of CT measurement, because of its lower cost and low exposure risk. Waist circumference stands as a reasonable surrogate of both methods, while W/H ratio is poorly correlated with other measures of body fat distribution.
BACKGROUND: The aim of the present study was to evaluate the safety and the efficacy of hepatic resection in the treatment of hepatolithiasis with intrahepatic biliary strictures. METHODS EXPERIMENTAL DESIGN: retrospective study. SETTING: University hospital, Italy. PATIENTS: 6 consecutive patients with single lobe hepatolithiasis operated on during the 4-year period 1994-98 inclusive. INTERVENTIONS: major hepatic resections (3 left hepatectomies, 2 left lobectomies, 1 right hepatectomy). MAIN OUTCOME MEASURES: type and duration of the surgical procedure, intra/postoperative blood losses, intra/postoperative course and complications, pathology, and hepatolithiasis recurrence. RESULTS: Mean operative time was 3.34+/-0.02 hrs (range 3.0-4.3 hrs). Mean blood loss was 233+/-150 ml (range 100-500 ml). No patient required intra/postoperative blood transfusions. No intraoperative complication was recorded. Mean postoperative hospitalization was 17+/-7 days (range 6-28 days). Postoperative course was uneventful in 4 (66%) cases. No postoperative mortality was recorded. One pancreatitis and 1 biliary fistula occurred, for an overall postoperative morbidity of 33%. Pathology showed cholangiocarcinoma in 2 cases (33%). During the follow-up period (range 3-48 months, mean 19.1+/-16.4 months), 1 patient had recurrent cholangitis due to right lobe lithiasis and 1 patient died for cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis and unreversible biliary strictures or possible presence of cholangiocarcinoma. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.
BACKGROUND AND AIMS: The subtype and species related heterogeneity of beta adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. METHODS: Relaxation of muscle strips was measured in vitro. RESULTS: The following agonists had decreasing relaxing potency (effective concentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non-selective), terbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective). Isoprenaline and terbutaline were more potent on circular than taenia strips; CGP 12177 and SR 58611A weakly and partially relaxed taenia but had little effect on circular strips. The potency of isoprenaline on circular strips was greatly reduced by the beta(1) selective antagonist CGP 20712 (10(-7) mol/l), and less so by ICI 118551 (10(-7) mol/l, beta(2) selective). CGP 20712 and ICI 118551 together (both 3 x 10(-6) mol/l) had no effect on taenia relaxation by SR 58611A and rendered isoprenaline and terbutaline virtually inactive on circular strips, although not on taenia, which was relaxed at higher than control concentrations and maximally by isoprenaline. Propranolol, a beta(1), beta(2) non-selective antagonist, at high concentrations (10(-5) mol/l) prevented taenia relaxation by CGP 12177 and SR 58611A; its quantitative antagonism of isoprenaline (in common with that of CGP 12177 used as an antagonist) was competitive in circular strips but not on taenia. CONCLUSIONS: beta(1), beta(2), and beta(3) adrenoceptors are functionally detectable in the human colon; agonist stimulation of any one type relaxed taenia but only isoprenaline was fully effective at the beta(3) subtype.
INTRODUCTION: Since June 1996 we performed laparoscopic adjustable silicone gastric banding (LASGB), because of low invasivity, absence of malabsorption, reversibility, and postoperative regulation. MATERIALS AND METHODS: Criteria included body mass index (BMI) >40 or >35 with serious obesity-related conditions. 154 patients underwent LASGB. BMI ranged from 35 to 65.7 (mean 43.7+/-6.2). RESULTS: The laparoscopic procedure was successfully completed in 150 patients (97.4%). One patient was converted to the laparotomic procedure because of hepatomegaly; 4 patients had to be converted for gastric laceration during the laparoscopic approach. In one of these patients, the band was removed 7 days later for sepsis, followed by an uneventful postoperative course. The mean length of postoperative hospitalization was 2.3+/-0.9 days. Per cent of excess weight loss was 42.5+/-22.4 after 1 year. CONCLUSIONS: LASGB was feasible and effective.
1. The newly developed non-peptide neurotensin (NT)-receptor antagonists SR 48692 and SR 142948 were used to challenge NT responses of human colonic circular smooth muscle strips in vitro. The presence of NT1 and NT2 receptor transcripts in this tissue was tested by reverse transcriptase polymerase chain reaction (RT - PCR) analysis. 2. NT potently and dose-dependently contracted muscle strips, with significant regional differences in potency and efficacy between the transverse and distal colon: EC50, 3.6 and 7.5 nM; the maximal effect was 70 and 55% of 0.1 mM carbachol. Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 microm), levocabastine (10 microM) or tetrodotoxin (1 microM). 3. SR 142948 (10 nM - 1 microM) competitively antagonized NT responses in the transverse and distal colon with similar affinities: pA2 values 8.71 and 8.45, slopes 0.98 and 0.99. SR 48692 (10 nM - 10 microM) antagonized the NT response competitively in the distal colon (pA2 6.55, slope 0.79) and non-competitively in the transverse colon (pA2 8.0, slope 0.51). Neither compound had any agonist effect. 4. The fact that the specific antagonists prevented NT-evoked atropine- and tetrodotoxin-insensitive mechanical responses of colonic muscle strips is highly consistent with the presence in these tissues of non-neuronal NT receptors, whose heterogeneity in the transverse segment is supported by the non-competitive antagonism of SR 48692. The finding of NT1 receptor transcript in both transverse and distal colon suggests its identity with the lower affinity site disclosed functionally by SR 48692 in these segments.
1. Human in vitro preparations of transverse or distal colonic circular smooth muscle were potently and dose-dependently contracted by neurokinin A (EC50, 4.9 nM), the tachykinin NK2-receptor selective agonist [beta-Ala8]neurokinin A (4-10) ([beta-Ala8]NKA (4-10)) (EC50, 5.0 nM), neurokinin B (EC50, 5.3 nM) and substance P (EC50, 160 nM), but not by the tachykinin NK1-receptor selective agonist [Sar9Met(O2)11] substance P, or the NK3-receptor selective agonists, senktide and [MePhe7] neurokinin B. No regional differences between transverse and distal colon were observed in response to [beta-Ala8]NKA (4-10). 2. Atropine (1 microM) and tetrodotoxin (1 microM) did not significantly inhibit responses to [beta-Ala8]NKA (4-10), neurokinin A, substance P or neurokinin B. 3. The newly developed non-peptide antagonists for tachykinin NK2-receptors SR 48968, SR 144190 and its N-demethyl (SR 144743) and N,N-demethyl (SR 144782) metabolites, were used to challenge agonist responses, as appropriate. SR 144190 and the metabolites all potently and competitively antagonized the response to [beta-Ala8]NKA (4-10), with similar potency (Schild plot pA2 values 9.4, 9.4 and 9.3, slope = 1). SR 48968 antagonism was not competitive: the Schild plot slope was biphasic with a high (X intercept approximately 9.3) and a low (X intercept 8.4, slope 1.6) affinity site. Co-incubation of SR 48968 (10, 100 nM) and SR 144782 (10 nM) produced additive effects; in this experimental condition, SR 48968 apparent affinity (pKB) was 8.2. In addition, SR 144782 (0.1 microM) antagonized responses to neurokinin A, substance P and neurokinin B, with pKB consistent with its affinity for tachykinin NK2-receptors. The potent and selective NK1 and NK3-receptor antagonists, SR 140333 and SR 142801 (both 0.1 microM), failed to inhibit contractions induced by SP or NKB. 4. In conclusion, the in vitro mechanical responses of circular smooth muscle preparations from human colon are strongly consistent with the presence of non-neuronal tachykinin NK2-receptors, but not tachykinin NK1- or NK3-receptors. Our findings with SR 48968 suggest the existence of two tachykinin NK2-receptor subtypes, that it seems to distinguish, unlike SR 144190 and its metabolites. However, the precise nature of SR 48968 allotopic antagonism remains to be elucidated, since allosteric effects at the tachykinin NK2-receptor might well account for the complexity of the observed interaction.
We investigated the effect of the cannabinoid agonist (+)WIN-55212-2 on human ileum longitudinal smooth muscle preparations, either electrically stimulated or contracted by carbachol. Electrical field stimulation mostly activated cholinergic neurons, since atropine and tetrodotoxin (TTX), alone or coincubated, reduced twitch responses to a similar degree (85%). (+)WIN-55212-2 concentration-dependently inhibited twitch responses (IC50 73 nM), but had no additive effect with atropine or TTX. The cannabinoid CB1 receptor antagonist SR 141716 (pA2 8.2), but not the CB2 receptor antagonist, SR 144528, competitively antagonized twitch inhibition by (+)WIN-55212-2. Atropine but not (+)WIN-55212-2 or TTX prevented carbachol-induced tonic contraction. These results provide functional evidence of the existence of prejunctional cannabinoid CB1-receptors in the human ileum longitudinal smooth muscle. Agonist activation of these receptors prevents responses to electrical field stimulation, presumably by inhibiting acetylcholine release. SR 141716 is a potent and competitive antagonist of cannabinoid CB1 receptors naturally expressed in the human gut.
OBJECTIVE: To assess retrospectively the effectiveness and the safety of the conservative medical management of asymptomatic cocaine body-packers. DESIGN: Case series collected during twelve years (1980-1992). SETTING: Milan Airports Health Center. Department of Surgery and Intensive Care Unit of San Raffaele Hospital-University of Milan. PARTICIPANTS: 189 suspected cocaine body packers (143 male, 53 female), aged between 18-53 years, were brought to our observation by customs after disembarking at the Milan International Airports of Malpensa and Linate. 61 subjects (32%) turned to be carriers of packets containing cocaine (ovules). INTERVENTIONS: Medical conservative treatment, based on close clinical observation and light solid diet, free assumption of liquids and oily laxatives. Plain abdominal X-ray and ultrasound were performed for the diagnosis of cocaine packet ingestion and then repeated up to the complete evacuation of all ovules. Two laparotomies with surgical removal of ovules in symptomatic patients (bowel obstruction and acute cocaine intoxication due to the intraluminal rupture). MEASURES: Physical examination with neurological assessment every 8 hours and vital signs (including blood pressure, heart frequency and temperature) every 4 hours to detect complications (acute cocaine intoxication, bowel obstruction or perforation) secondary to cocaine packet ingestion. Structural features of the containers, cocaine amount per ovule, and rate and indications for surgical treatment have been reviewed. RESULTS: Evacuation period lasted from 3 to 6 days. Ingested containers varied from 52 to 117 with a mean of 88 +/- 13 ovules for each body packer. Total amount of recovered 95% pure cocaine hydrochloride was 41 kilograms. Signs of cocaine toxicity and bowel obstruction requiring emergency laparotomy occurred in two cases (3.3%). Both patients recovered uneventfully. CONCLUSIONS: Conservative management during spontaneous evacuation of the containers is the first choice approach to the body-packet ingestion. Close clinical observation allows an early detection of the patients with complications requiring emergency surgical treatment.
OBJECTIVE: To assess the role of interventional radiology in the conservative treatment of postoperative pancreatic fistula. CASE REPORT: A case of a high flow mixed entero-bilio-pancreatic fistula caused by dehiscence of pancreatic-jejunal anastomosis after duodenocephalopancreasectomy for endocrine neoplasm of the head of the pancreas, SETTING: General Surgery Division and Diagnostic Radiology. CONCLUSIONS: Conservative treatment represents at the time being, due to the current possibilities in assisting critical patients and in controlling pancreatic secretory activity, the first choice in pancreatic fistula treatment. The effectiveness of this treatment depends on the severity of inflammatory disease of the pancreas. Clinical (Ranson, Glasgow, APACHE II) and radiological (Balthazar, Vernacchia) parameter evaluation is a critical step in therapeutic choice. Surgery should be used in patients with severe pancreatitis. Conservative treatment represents the first choice in stable and critical patients with mild pancreatitis.
RATIONALE AND OBJECTIVES: We monitored the regeneration of the rat sciatic nerve after its transection and the concomitant alteration in the high-energy phosphates content in the target tibialis anterior muscle. METHODS: Rat sciatic nerve was resected and the gap connected with a prosthesis of polytetrafluoroethylene. Progress of reinnervation was monitored by 1H MR imaging, whereas muscular energy metabolism was evaluated by localized 31P MR spectroscopy. RESULTS: Reconstitution between the nerve stumps was resumed 8-12 weeks postoperatively. The ratio of phosphocreatine to inorganic phosphate reached a plateau at 46% of the initial level approximately 8 weeks after the operation and recovered thereafter. Immediately after the surgery, muscular pH became slightly alkaline and returned to normal with the progress of reinnervation. CONCLUSION: Recovery of the muscular energy metabolism began after the reconnection of the severed nerve stumps. The combination of MR imaging and MR spectroscopy followed noninvasively the progress of reinnervation and muscular energy metabolism of the prosthesis-guided nerve regeneration.
OBJECTIVE: To assess retrospectively the effectiveness, the safety and the impact on the quality of life of the Subcutaneous Infusion Ports (SIPs) for prolonged venous access in the treatment of neoplastic patients. DESIGN: Retrospective analysis of a case series collected-during 30 months (April 1991-September 1993). SETTING: General Surgery Division and Radiochemotherapy Service. PARTICIPANTS: 35 patients (23 male, 12 female), aged between 27-80 years, received 37 SIPs. 2 patients received 2 SIPs. 34 patients were affected by neoplasm; 1 patient had short gut syndrome secondary to massive small bowel resection. INTERVENTIONS: The SIP was implanted in all patients in the operating room with the Seldinger technique ("catheter over wire"). The suclavian vein, through an infraclavicular approach, was the only site of venous access. One SIP was implanted in the hepatic artery. All neoplastic patients received chemotherapy. The patient with short gut syndrome had parenteral nutrition. An external infusion device (CADD-1, CADD-plus, Pharmacia) was used in 13 patients for the continuous infusion of either 5-Fluoro-Uracil (1000 mg/m2/die for 5 days, every 28 days) or 5-Fluoro-Deoxy-Uridine (0.15-0.30 mg/kg/die for 14 days, every 28 days). SIP management required the port "flush" with normal saline solution with heparin (100 U/ml) at least every 40 days, using Huber needle. All patients were treated as outpatients. MAIN OUTCOME MEASURES: All intraoperative and long-term complications, recorded in the charts of the patients, were reviewed. The rate of intraoperative complications was assessed over 37 procedures. Long-term complications were assessed over 28 patients (7 patients were excluded for lack of follow up data). Incidence of complications was analyzed over patient days, considering the cumulative permanence time of the SIP in a single patient. RESULTS: We recorded 4 intraoperative complications (10.8%). None of them required to stop the procedure and to delay the implant of the SIP. During the follow-up period (range 1-18 months) we had 1 major complication (pleural effusion secondary to TPN extravasation), that is 3.5% of the patients (1/8255 patient days), and 3 minor complications (10.7% of the patients; 1/2751.6 patient days). Patient tolerance was good in all cases. CONCLUSIONS: SIP is a safe and effective device for prolonged venous access. We stress the need of a wider use of this type of device for the management of neoplastic patients.
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During the last decade, the increase of drug traffic and close customs' control have led smugglers to attempt various methods to pass through customs undetected. One method is the ingestion of large numbers of drug-filled packets (usually containing cocaine), together with anticholinergics inhibiting intestinal peristalsis, by a smuggler, called "body-packer" or "mule". The up-to-date approach to cocaine-packet ingestion is conservative medical management during the spontaneous evacuation of the "ovules". Emergency surgical treatment should be reserved for the complications of cocaine-packet ingestion ("body packer syndrome"), which are bowel obstruction due to clustering of the containers and intraluminal rupture of the "ovules" with massive drug transmucous absorption (acute cocaine intoxication). We describe a case of cocaine-packet ingestion in a 19 year old man who was asymptomatic at admission and thus conservatively treated. During the spontaneous evacuation of ovules, clinical and radiological signs of bowel obstruction appeared and the patient underwent emergency laparotomy with removal of 21 containers, two of them clustered in the distal ileum, causing the occlusion. This case gave reasons for a discussion on the specific features of bowel obstruction in cocaine packet ingestion. The bowel obstruction of cocaine-packet ingestion should be carefully considered and promptly treated because of the potentially lethal consequences (death rate of 56% of cases) of transmucous absorption of cocaine contained in "ovules". In fact, while opioid intoxication can be fought with specific antagonists towards opioid receptors (naloxone), the lack of a specific antidote makes cocaine poisoning particularly dangerous.(ABSTRACT TRUNCATED AT 250 WORDS)