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Biomedical subjects

S Gobbi

Publications and source records attributed to S Gobbi.

At least 19 recordsLinked to original sources
PubMed2003

Scoring system to predict asymptomatic choledocholithiasis before laparoscopic cholecystectomy. A matched case-control study.

BACKGROUND: The purpose of this prospective study was to evaluate if a recently proposed score system based on six preoperative parameters [history of colic pain and/or jaundice, dyspepsia, cholecystitis, ultrasound (US), evidence of common bile duct stones (CBDS), number and size of gallbladder stones at US, level of serum glutamic oxalacetic transaminase and/or alkaline phosphatase is effective in the selection of patients undergoing laparoscopic cholecystectomy (LC) with asymptomatic CBDS and could allow a significant reduction of the total number of preoperative examinations. METHODS: In the case group, 408 patients were categorized into low-, medium-, and high-risk classes and underwent, respectively, no further preoperative assessment of the bile duct, intravenous cholangiography (IVC), and endoscopic retrograde cholangiography (ERC). Intraoperative cholangiography (IOC) was performed whenever the surgeon was in doubt as to biliary anatomy or bile duct clearance. These patients were compared with 408 retrospectively matched patients (control group) undergoing routine preoperative IVC and/or ERC. RESULTS: In the case group, significantly lower numbers of IVC (120 vs 392) and IOC (3 vs 16) were performed ( p < 0.005), whereas no difference in the total number of ERCs was noted. One patient in the control group had retained CBDS detected during follow-up evaluation, whereas none occurred in the case group. CONCLUSION: The proposed scoring system allows selective use of IVC, ERC, and/or IOC in patients undergoing elective LC.

Adult↗
PubMed2003

Randomized clinical trial of laparoscopic cholecystectomy performed with mini-instruments.

BACKGROUND: The outcomes after traditional laparoscopic cholecystectomy (LC; one 10-mm port, one 12-mm port and two 5-mm ports) and minilaparoscopic cholecystectomy (MLC; three 3-mm ports and one 12-mm port) for gallstone disease were compared. METHODS: The study was a randomized, single-blind trial comparing LC with MLC. Only elective patients were eligible for inclusion. LC was a routine procedure at the institution in which the study was performed, whereas MLC was introduced after a short training period. The randomization period was from January to December 2001. RESULTS: Of 175 patients who had elective minimal access cholecystectomy during the randomization period, 135 entered the trial: 68 underwent LC and 67 underwent MLC. The groups were matched for age, sex and preoperative characteristics. Median (range) operating times for LC and MLC were similar (45 (20-120) and 50 (20-170) min respectively). Intraoperative and postoperative complication rates, the time for the patient to resume walking, eating and passing stools, and median hospital stay were the same in the two groups. The level of postoperative pain was lower in the MLC group at 1 h (P = 0.011), 3 h (P = 0.012), 6 h (P = 0.003), 12 h (P = 0.052) and 24 h (P = 0.034). Patients who had MLC received fewer injections of analgesic (P = 0.036) and more patients in this group expressed satisfaction with the cosmetic result (P = 0.001). CONCLUSION: MLC took a similar time to perform and caused less postoperative pain than the standard laparoscopic procedure. Reducing the port size further enhanced the advantages of laparoscopic over open cholecystectomy.

Cholecystectomy, Laparoscopic↗
PubMed2003

Neuropathy as the only symptom of common carotid artery spontaneous rupture. Case report.

We describe a case of a false aneurysm of the common carotid artery, caused by spontaneous carotid rupture, with atypical clinical presentation. The patient came to the our Hospital complaining of left shoulder pain and functional impairment of her left arm, during the past 20 days. The diagnostic work-up, color Doppler ultrasound, MR and angiography, evidenced a cervical false aneurysm; the electromyography showed denervation of the deltoid muscle, caused by cervical nerve roots compression. The therapeutic stages were initially an endovascular stent placement; then a surgical stage with evacuation for the hematoma and reconstruction of the carotid artery with saphenous graft.

Aneurysm, False↗
PubMed2001

Acetylcholinesterase inhibitors: SAR and kinetic studies on omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl derivatives.

In this work, we further investigated a class of carbamic cholinesterase inhibitors introduced in a previous paper (Rampa et al. J. Med. Chem. 1998, 41, 3976). Some new omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl analogues were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The structure of the lead compound (xanthostigmine) was systematically varied with the aim to optimize the different parts of the molecule. Moreover, such a structure-activity relationships (SAR) study was integrated with a kinetic analysis of the mechanism of AChE inhibition for two representative compounds. The structural modifications lead to a compound (12b) showing an IC(50) value for the AChE inhibition of 0.32 +/- 0.09 nM and to a group of BuChE inhibitors also active at the nanomolar level, the most potent of which (15d) was characterized by an IC(50) value of 3.3 +/- 0.4 nM. The kinetic analysis allowed for clarification of the role played by different molecular moieties with regard to the rate of AChE carbamoylation and the duration of inhibition. On the basis of the results presented here, it was concluded that the cholinesterase inhibitors of this class possess promising characteristics in view of a potential development as drugs for the treatment of Alzheimer's disease.

Acetylcholinesterase↗
PubMed2001

A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase.

Aromatase (P450arom) is a target of pharmacological interest for the treatment of breast cancer. In this paper, we report the design, synthesis, and in vitro biological evaluation of a series of new (di)benzopyranone-based inhibitors of this enzyme. The design of the new compounds was guided by a CoMFA model previously developed for a series of nonsteroidal aromatase inhibitors. Both the chromone and the xanthone nuclei were taken as molecular skeletons, and the functions supposed to be critical for binding to the aromatase active site - a heterocyclic ring (imidazole or 1,3,4-triazole) linked to the aromatic moiety by a methylene unit and an H-bond accepting function (CN, NO(2), Br) located on the aromatic ring at a suitable distance from the heterocyclic nitrogen carrying the lone pair--were attached to them. The chromone, xanthone, and flavone derivatives were prepared by conventional synthetic methods from the appropriate methyl analogues. Aromatase inhibitory activities were determined by the method of Thompson and Siiteri, using human placental microsomes and [1 beta,2 beta-(3)H]testosterone as the labeled substrate. All the compounds were also tested on 17 alpha-hydroxylase/C17,20-lyase (P450 17), an enzyme of therapeutic interest for the treatment of prostatic diseases. The goal to find new potent inhibitors of aromatase was reached with the xanthone derivatives 22d,e (IC(50) values 43 and 40 nM, respectively), which exceeded the potency of the known reference drug fadrozole and also showed high selectivity with respect to P450 17. Moreover, compounds 22g-i based on the same xanthonic nucleus showed fairly high potency as P450 17 inhibitors (IC(50) values 220, 130, and 42 nM, respectively). Thus, they might be new leads for the development of drug candidates for androgen-dependent diseases.

Aromatase Inhibitors↗
PubMed2000

Laparoscopically assisted treatment of acute abdomen in systemic lupus erythematosus.

The incidence of abdominal pain in patients with systemic lupus erythematosus (SLE) is very high. Most patients do not require surgical treatment (serositis). Some cases such as appendicitis, perforated ulcer, cholecystitis or, rarely, intestinal infarction are surgical. Differential diagnosis is difficult, partly because noninvasive examinations do not provide enough evidence to rule out a diagnosis. On the other hand, in patients with SLE who have acute abdomen, it is dangerous to delay surgery by attempting conservative therapy. In fact, a better survival rate has been associated with early laparotomy. We report a case of acute abdomen in a patient affected by SLE, in which the diagnostic problem was solved by means of laparoscopy and the treatment was laparoscopically assisted. A 45-year-old woman with a 25-year history of SLE was admitted with abdominal pain and fever. Her physical examination revealed a painful right iliac fossa with rebound tenderness. Her WBC count was normal. Abdominal x-ray, ultrasonography, paracentesis, and peritoneal lavage did not provide a diagnosis. A diagnostic laparoscopy was performed, showing segmentary small bowel necrosis. The incision of the umbilical port site was enlarged to allow a small laparatomy, and a small bowel resection was performed. The histopathologic finding was "leucocytoclasic vasculitis, with infarction of the intestinal wall." The patient recovered uneventfully. In conclusion, this case report shows that emergency diagnostic laparoscopy is feasible and useful for acute abdomen in SLE. Currently, this diagnostic possibility could be considered the technique of choice in these cases, partly because, when necessary, it also can allow for mini-invasive treatment therapy.

Abdomen, Acute↗
PubMed2000

SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues.

In this study, we attempted to derive a comprehensive SAR picture for the class of acetylcholinesterase (AChE) inhibitors related to tacrine, a drug currently in use for the treatment of the Alzheimer's disease. To this aim, we synthesized and tested a series of 9-amino-1,2,3,4-tetrahydroacridine derivatives substituted in the positions 6 and 7 of the acridine nucleus and bearing selected groups on the 9-amino function. By means of the Hansch approach, QSAR equations were obtained, quantitatively accounting for both the detrimental steric effect of substituents in position 7 and the favorable electron-attracting effect exerted by substituents in positions 6 and 7 of the 9-amino-1,2,3,4-tetrahydroacridine derivatives. The three-dimensional (3D) properties of the inhibitors were taken into consideration by performing a CoMFA analysis on the series of AChE inhibitors made by 12 9-amino-1,2,3, 4-tetrahydroacridines and 13 11H-indeno[1,2-b]quinolin-10-ylamines previously developed in our laboratory. The alignment of the molecules to be submitted to the CoMFA procedure was carried out by taking advantage of docking models calculated for the interactions of both the unsubstituted 9-amino-1,2,3,4-tetrahydroacridine and 11H-indeno[1,2-b]quinolin-10-ylamine with the target enzyme. A highly significant CoMFA model was obtained using the steric field alone, and the features of such a 3D QSAR model were compared with the classical QSAR equations previously calculated. The two models appeared consistent, the main aspects they had in common being (a) the individuation of the strongly negative contribution of the substituents in position 7 of tacrine and (b) a tentative assignment of the hydrophobic character to the favorable effect exerted by the substituents in position 6. Finally, a new previously unreported tacrine derivative designed on the basis of both the classical and the 3D QSAR equations was synthesized and kinetically evaluated, to test the predictive ability of the QSAR models. The 6-bromo-9-amino-1,2,3,4-tetrahydroacridine was predicted to have a pIC(50) value of 7.31 by the classical QSAR model and 7.40 by the CoMFA model, while its experimental IC(50) value was equal to 0.066 (+/-0.009) microM, corresponding to a pIC(50) of 7.18, showing a reasonable agreement between predicted and observed AChE inhibition data.

Chemical Phenomena↗
PubMed2000

Laparoscopic diagnosis of gallbladder agenesis.

In this article, we report two cases of gallbladder agenesis that were incorrectly diagnosed as cholelithiasis on preoperative sonography. In the first case, the diagnosis was made by laparoscopic surgery and confirmed by postoperative CT scan. The second case was confirmed by laparoscopic abdominal examination and by laparoscopic sonography. Both patients had undergone preoperative IV cholangiography. Preoperative cholangiography and laparoscopic exploration completed by laparoscopic sonography should be considered adequate modalities for the diagnosis of gallbladder agenesis, without the need for laparotomy and thorough postoperative workup.

Adult↗
PubMed2000

Does laparoscopic cholecystectomy worsen the prognosis of unsuspected gallbladder cancer?

BACKGROUND: Several reports claim that there is a risk that laparoscopic cholecystectomy (LC) might worsen the prognosis of unsuspected gallbladder cancer. HYPOTHESIS: Several factors rather than LC could influence prognosis. METHODS: A retrospective clinicopathologic study was performed on 20 patients, 9 patients (3 men and 6 women, aged from 36 to 75 years [mean age, 62.3 years]) undergoing LC and 11 patients (2 men and 9 women, aged from 53 to 91 years [mean age, 65.3 years]) undergoing open cholecystectomy (OC), with postoperatively diagnosed gallbladder cancer. The correlation was evaluated between cumulative survival rates and the following 7 prognostic factors: age, sex, histopathological grade, pathologic stage, occurrence of bile spillage, type of cholecystectomy (LC or OC), and additional surgical treatments. RESULTS: Seven patients (87%) after LC and 9 patients (82%) after OC had cancer recurrence: the difference is of no statistical significance (P =.9). There were no recurrences of cancer in the abdominal wall after either LC or OC. Survival rate was statistically correlated to tumor stage (P =.007) and to the occurrence of bile spillage (P =.002). Survival rate did not change according to whether the operation was carried out using LC or OC (P =.60). CONCLUSION: These results would seem to lend support to the opinion that LC does not worsen the prognosis for unsuspected gallbladder cancer.

Aged↗
PubMed2000

Five-year prospective audit of routine intravenous cholangiography and selective endoscopic retrograde cholangiography with or without intraoperative cholangiography in patients undergoing laparoscopic cholecystectomy.

Consensus has never been reached regarding the need or the imaging technique for evaluating the common bile duct (CBD) in patients considered for cholecystectomy. With the advent of laparoscopic cholecystectomy there has been a resurgence of interest in the role of preoperative intravenous cholangiography (IVC) as an alternative for evaluating the CBD. The purpose of this audit was to assess whether a diagnostic workup based on IVC, which permits selective use of intraoperative cholangiography (IOC) and endoscopic treatment of CBD stones before surgery, could be useful in patients undergoing laparoscopic cholecystectomy (LC). In patients without jaundice, gallstone pancreatitis, a prior diagnosis of CBD stones, a prior history of contrast allergy, or a risk of contrast-associated acute renal failure, IVC was performed routinely. Patients suspected to have CBD stones based on IVC results or with inconclusive IVC and patients with a strong clinical suspicion of CBD stones were referred for endoscopic retrograde cholangiography (ERC). IOC was carried out in patients who had a history of contrast allergy or risk of contrast-associated acute renal failure and whenever the surgeon was in doubt as to the biliary anatomy or CBD clearance. IVC was carried out in 1155 patients, ERC in 225, and IOC in 54. IVC was conclusive in 1132 patients, with a diagnostic accuracy of 99%. Our workup permitted the sequential endoscopic-laparoscopic treatment of cholecystocholedocholithiasis in 162 cases. During the follow-up period residual CBD stones were detected in four patients. Our diagnostic workup showed that routine IVC exposes the population to a large radiation burden, and the cost is high for the small number of patients who benefit. Moreover, it does not seem helpful in reducing the incidence of CBD injuries during LC.

Adolescent↗
PubMed2000

Synthesis and biological activity of some rigid analogues of flavone-8-acetic acid.

Some rigid analogues of flavone-8-acetic acid are described. Direct in vitro toxicity of the synthesised compounds was evaluated towards four tumoral cell lines and the ability of these compounds to stimulate mouse peritoneal macrophages in culture to become tumoricidal (indirect toxicity) was also studied. All compounds were able to induce direct cytotoxicity only at very high concentrations but showed a remarkable indirect activity. In particular compound 4d was able to significantly increase macrophage lytic properties and has been selected for further investigations.

Animals↗
PubMed2000

Acetylcholinesterase inhibitors for potential use in Alzheimer's disease: molecular modeling, synthesis and kinetic evaluation of 11H-indeno-[1,2-b]-quinolin-10-ylamine derivatives.

Continuing our work on tetracyclic tacrine analogues, we synthesized a series of acetylcholinesterase (AChE) inhibitors of 11H-indeno-[1,2-b]-quinolin-10-ylaminic structure. Selected substituents were placed in synthetically accessible positions of the tetracyclic nucleus, in order to explore the structure-activity relationships (SAR) and the mode of action of this class of anticholinesterases. A molecular modeling investigation of the binding interaction of the lead compound (1a) with the AChE active site was performed, from which it resulted that, despite the rather wide and rigid structure of 1a, there may still be the possibility to introduce some small substituent in some positions of the tetracycle. However, from the examination of the experimental IC50 values, it derived that the indenoquinoline nucleus probably represents the maximum allowable molecular size for rigid compounds binding to AChE. In fact, only a fluorine atom in position 2 maintains the AChE inhibitory potency of the parent compound, and, actually, increases the AChE-selectivity with respect to the butyrylcholinesterase inhibition. By studying the kinetics of AChE inhibition for two representative compounds of the series, it resulted that the lead compound (1a) shows an inhibition of mixed type, binding to both the active and the peripheral sites, while the more sterically hindered analogue 2n seems to interact only at the external binding site of the enzyme. This finding seems particularly important in the context of Alzheimer's disease research in the light of recent observations showing that peripheral AChE inhibitors might decrease the aggregating effects of the enzyme on the beta-amyloid peptide (betaA).

Acetylcholinesterase↗
PubMed2000

Is tumour angiogenesis a prognostic factor in patients with colorectal cancer and no involved nodes?

OBJECTIVE: To examine a possible association between tumour angiogenesis and conventional prognostic variables and to assess the prognostic value of the variables examined in patients with colorectal cancer, with no involved nodes. DESIGN: Retrospective study. SETTING: University hospital, Italy. SUBJECTS: 119 patients who had had colorectal cancers resected for cure with no involved nodes between 1985-1990. INTERVENTIONS: The three microscopic fields with the most microvessels were identified by immunohistochemical techniques. 10 high-power fields in each area were used for the microvessel count and the mean values indicated the microvessel density. MAIN OUTCOME MEASURES: Correlation of microvessel density with conventional prognostic factors, recurrence rates, and survival. RESULTS: There was a significant correlation between microvessel density and sex, women having a higher density than men (p < 0.05), but no significant correlations between density and recurrence rates or survival. Multivariate analysis did not indicate that microvessel density had a prognostic role. CONCLUSION: Microvessel density in colorectal cancer without involved nodes does not correlate with conventional prognostic factors and provides no prognostic information.

Aged↗
PubMed2000

Asymptomatic bile duct stones: selection criteria for intravenous cholangiography and/or endoscopic retrograde cholangiography prior to laparoscopic cholecystectomy.

OBJECTIVE: Routine use of endoscopic retrograde cholangiography (ERC) and/or intravenous cholangiography (IVC) or magnetic resonance cholangiopancreatography (MRCP) before laparoscopic cholecystectomy (LC) is not cost-effective. The objective of this study was to determine precise and easily applicable criteria to select patients who should undergo IVC, MRCP and/or ERC before LC. DESIGN AND METHODS: Prospectively collected data from 74 consecutive patients who were diagnosed with asymptomatic common bile duct stones (CBDS) before undergoing LC, were compared with data from 74 matched controls without CBDS. Using the chi2 test, those variables were identified which were significantly related to the presence of CBDS. These were inserted into a logistic multiple regression model and, by means of conditional regression analysis, each variable was assigned a score from -2 to +4 proportional to the odds ratio. By adding up the scores obtained, a classification was made as to high, medium and low CBDS risk. RESULTS: As a result, 51 patients were found to be low-risk cases, 53 medium-risk and 44 high-risk. Assuming no further assessment of the bile duct needed to be carried out in low-risk patients, an IVC or MRCP in those at medium risk and an ERC in those at high risk, a calculation was made of the positive predictive value and the sensitivity of the system proposed. The positive predictive value and the sensitivity of the procedure were calculated as being greater than 90%. CONCLUSIONS: This predictive system for the risk of CBDS allows the selective use of ERC, IVC and MRCP to ensure a high yield and improve cost-effectiveness. A controlled prospective study will verify these results.

Adolescent↗
PubMed1999

Routine intravenous cholangiography, selective ERCP, and endoscopic treatment of bile duct stones before laparoscopic cholecystectomy.

BACKGROUND: No procedure has yet been identified as the standard for the detection and management of choledocholithiasis in patients undergoing laparoscopic cholecystectomy. METHODS: A prospective study involved 1305 patients undergoing elective laparoscopic cholecystectomy. Intravenous cholangiography was performed on all patients except those with jaundice or cholangitis, acute pancreatitis, or allergy to contrast material. Patients underwent endoscopic retrograde cholangiography (ERC) and endoscopic sphincterotomy when there was a strong suspicion of choledocholithiasis, positive or inconclusive findings on intravenous cholangiography or allergy to contrast material with signs of possible choledocholithiasis. Intraoperative cholangiography was performed when patients did not undergo ERC or intravenous cholangiography and whenever the surgeon was in doubt about biliary anatomy or biliary clearance. RESULTS: Two hundred thirty-one patients (17.7%) were referred for preoperative ERC; 14 of them were referred for open surgery because of failure of ERC or sphincterotomy. Only 54 patients underwent intraoperative cholangiography. Bile duct stones, detected in 186 cases (14.2%) (68 of which were asymptomatic), were removed before surgery in 162 cases (87.1%) and during surgery in 20 (10.7%). Self-limited pancreatitis occurred in 3.6% of the patients after sphincterotomy. Laparoscopic cholecystectomy was performed in 98.7% of the cases. The conversion rate was 8% if sphincterotomy had been performed previously, and 3% after standard laparoscopic cholecystectomy (p < 0.001). The morbidity rate was 5% and the mortality rate 0.08%. During the follow-up period 4 patients had retained stones that were treated endoscopically. CONCLUSIONS: Preoperative ERC followed by laparoscopy is the best approach to treatment of patients with cholecystolithiasis and suspected choledocholithiasis.

Adolescent↗
PubMed1999

Incidental gallbladder cancer at laparoscopy: a review of two cases.

Early peritoneal seeding and trocar site metastasis from gallbladder cancer have been reported after laparoscopic cholecystectomy. Nevertheless, the role of laparoscopy in gallbladder cancer remains controversial. Two cases of early recurrence of carcinoma of the gallbladder after laparoscopic cholecystectomy are described. In the first case, the use of a gasless technique did not prevent an early, diffuse peritoneal dissemination of the disease. In the second case, despite the use of a retrieval bag to extract the gallbladder, multiple metastases around the gallbladder bed and local peritoneal seeding developed. These cases demonstrate that factors other than bile spillage, CO2 inflation, and the use of a retrieval bag are responsible for early dissemination of gallbladder cancer.

Adenocarcinoma↗
PubMed1998

Synthesis of flavone-2'-carboxylic acid analogues as potential antitumor agents.

Some flavone-2'-carboxylic acid analogues are described. Direct in vitro toxicity of the synthesized compounds was evaluated towards four tumoral cell lines, and the ability of these compounds to stimulate mouse peritoneal macrophages in culture to become tumoricidal (indirect toxicity) was also studied. Direct cytotoxic activity was very low for all derivatives. However, almost all compounds showed a remarkable increase of indirect cytotoxicity. In particular, compound 3i, which has an F atom in the 7 position of the flavone ring, was able to increase significantly the macrophage's lytic properties, and has been selected for further investigations.

Adjuvants, Immunologic↗