Cholecystoduodenal fistula in a nonagenarian. Can laparotomy play a role in the era of laparoscopic? Case report.

Cholecystoduodenal fistula, a rare complication of biliary lithiasis, occurs in 0.5% to 3% of patients affected by cholelithiasis. Diagnosis is not easy and is usually incidental at surgery. The literature guidelines call for a laparoscopic approach to treating these patients; here, however, we report a case of a very elderly patient in which, among other reasons, open surgery was the treatment of choice to decrease morbidity and mortality.

Isolated hydatid cyst of the diaphragm without liver or lung involvement: a case report.

The most common targets of the echinococcus are the liver and the lung, but several organs can be affected by this disease. The isolated diaphragmatic location of the cyst, not associated with liver or lung, is very rare. The aim of this work is to report a case of hydatid cyst located in the abdominal side of the diaphragm and to review the literature. The diagnosis was fortuitous and at CT scan the cyst was apparently located on segment VII of the liver. During surgery, after dissection of the adherences with the liver, the cyst remained attached to the diaphragm. Thirty months after the resection, the patient is free of symptoms without any recurrence.

Emergency gastric ulcer complications in elderly. Factors affecting the morbidity and mortality in relation to therapeutic approaches.

AIM: In elderly the incidence of the emergency gastric ulcer complications, perforation and bleeding are increasing, with a difficult management of these patients for their concomitant diseases. The aim of this work is to analyze the therapeutical approach of emergency gastric ulcer complications in elderly patients, in order to establish the factors affecting the morbidity and mortality. METHODS: Patients older than 70 years, presenting gastric ulcer, observed in a tertiary University Hospital from 1995 to 2003, have been considered for the present study. Two groups of diseases have been examined: ulcer perforation and bleeding ulcer. Age, sex, risk factors, comorbidity, methods of diagnosis, ulcer characteristics, treatment, morbidity, mortality, hospitalization time and follow-up have been considered in each group. RESULTS: Thirteen elderly patients with perforated gastric ulcer have been observed: 9 (69.2%) females and 4 (30.8%) males with a mean age of 80.5 years (range 70-90). Four patients were hospitalized in suburban hospital with an average time between the diagnosis and the surgery of 36 h, while the remnants were hospitalized directly in our Department with a medium waiting time of about 2 h. The surgical procedures were: simple closure with omentum patch in 11 cases (84.6%), and antrectomy in 2 cases (15.4%), in which the antrum was multiply perforated. Two patients presented an ulcer larger than 2 cm treated with simple suture and omental patch without morbidity and mortality. Three patients (23%) died postoperatively, due to septic shock, ventricular fibrillation and intraoperative massive haemorrhage, 2 of these patients came from other hospitals. Twenty-eight elderly patients with bleeding gastric ulcer have been observed during the same period: 13 (46.4%) females and 15 (53.6%) males with a mean age of 79.6 years (range 71-91). Except 2 patients submitted to endoscopic treatment both with adrenaline injection, all the remnant patients were managed with medical therapy (H2-receptor antagonist or proton pump inhibitors and in 7 patients [24.1%] antihaemorrhage drugs), and clinical observation, with a endoscopic control 3-4 days after from the first endoscopy. One of the 2 patients endoscopically treated developed a ulcer perforation after 11 days, and the other one rebled, without possibility of any kind of treatment due to his instable condition of health. Three patients (10.7%) died during their hospital stay not for causes strictly due to the gastric haemorrhage. CONCLUSIONS: Our results suggest that the early diagnoses and early treatment are 2 basic factor on the prognosis of elderly patients with perforated gastric ulcer. The choice between simple closure, with or without vagotomy, or gastrectomy depends from preoperative and operative health conditions of the patient. In patients with ulcer larger than 2 cm, Graham's technique can be performed safely if the preoperative and intraoperative conditions are favourable. Elderly patients with gastric ulcer bleeding show an high risk of morbidity and mortality, related to the risk factors like non steroid anti-inflammatory drugs (NSAIDs) intake or smoke. Repeated endoscopy and antiulcer drugs can manage the high stage patients of Forrest's classification with a low rate of morbidity and mortality. According to literature surgical treatment should be reserved after the second failure of endoscopic treatment.

[Assessment of patient's comfort and functioning of a totally implantable venous system placed in the safenous vein]. / Valutazione del comfort del paziente e della funzionalità di un sistema totalmente impiantabile venoso posizionato in vena safena.

BACKGROUND: When venous system of superior vena cava is not useful or when chest wall is not utilizable to place a reservoir, saphenous vein can be utilized for totally implantable venous access device (TIVAD) placement. Aim of this work is to establish the best location of the reservoir for the function and the comfort of the patient. PATIENTS AND METHODS: All the patients submitted to TIVAD placement from January 1995 to October 2004 at the Department of Surgical Science, Organs Transplantations and Advanced Technologies of University of Catania have been considered to the present study. Age, sex, kind of disease, surgical procedure, early and late complications, function of the system and comfort to the patients in relation to the different site of reservoir placement have been studied. RESULTS: 447 TIVAD have been implanted in 258 males and 189 females aged from 31 to 79 years in the period considered for the study. Solid tumors represent the majority of the indications and all the TIVAD have been implanted by surgical cutdown to avoid all the early complications related to the percutaneous approach. Two patients received their TIVAD using saphenous vein by surgical cut-down, and no early complications have been recorded. The reservoirs have been placed respectively: in the chest wall in the first patient; and in the anterior wall of the abdomen, close to the anterosuperior iliac crest, firstly and later in the anterolateral face of the thigh in the second one. The first patient had non complications instead the second one referred discomfort with both reservoir locations. CONCLUSIONS: For the comfort of the patient related to the reservoir position in case of saphenous vein utilization chest wall should represent the best studies are required to validate the appropriate reservoir location.

[Use of the Floating Ball for hepatic resection in cirrhotic patients affected by hepatocellular carcinoma]. / Utilizzo del floating Ball nella chirurgia resettiva del carcinoma epatocellulare in pazienti cirrotici.

Done to the improvement of knowledges in hepatic surgery and postoperative care, hepatocellular carcinoma (HCC) have been treated more and more frequently by hepatic resection. Aim of this study is to report an initial series of patients affected by HCC treated by hepatic resection utilizing a new water-cooled, high-density, monopolar device, the Tissuelink Monopolar Floating Ball (Tissuelink Medical Inc., Dover, NH, U.S.A.), in order to avoid bleeding during hepatic surgery. Sex, age, kind of disease, viral and Child status, type of surgical procedure, in association to lenght of surgical procedure, blood loss, utilization of the vascular clamping of the liver, hospital stay, morbidity and mortality have been analized. Six liver resections have been performed utilizing this new device. No vascular clamping was established except one. No mortality was recorded. Morbidity was ascites in one case and pleural effusion in a second one. In conclusion the Floating Ball reduces the intraoperative bleeding during hepatic resection in patients with HCC.

Cytotoxicity in vitro and preliminary antitumor activity in vivo of a novel organotin compound.

The cytotoxic effect and antitumor activity induced by the novel organotin compound triethyltin(IV)lupinyisulfide hydrochloride, have been investigated. Different patterns of antiproliferative effects have been observed in a panel of human tumor cell lines in vitro. Toxicity studies in mice reported acute toxicity at the doses of 21 and 17.5 mg/kg which progressively disappeared at lower concentrations. On this basis, the doses of 3.5, 7 and 14 mg/kg were selected to assess the antitumor activity in vivo against the P388 leukemic cells xenografted in mice. This compound was able to induce a dose-dependent significant reduction of tumor volume, up to 46%, at the highest concentration (p = 0.0062) without important toxicity, as also confirmed by histological analysis of the main organ tissues. This preliminary study seems to hold interest for further investigations in different tumor models as well as for the evaluation of optimal drug route and schedule.

Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride.

Organotin compounds, particularly tri-organotin, have demonstrated cytotoxic properties against a number of tumor cell lines. On this basis, triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29), a quinolizidine derivative, was synthesized and developed as a potential antitumor agent. This tin-derived compound exhibited potent antiproliferative effects on three different human cancer cell lines: teratocarcinoma of the ovary (PA-1), colon carcinoma (HCT-8) and glioblastoma (A-172). Cytotoxic activity was assessed by MTT and cell count assays during time course experiments with cell recovery after compound withdrawal. Significant cell growth inhibition (up to 95% in HCT-8 after 72 h of exposure), which also persisted after drug-free medium change, was reported in all the cell lines by both assays. In addition, the cytocidal effects exerted by IST-FS 29 appeared more consistent with necrosis or delayed cell death, rather than apoptosis, as shown by morphologic observations under light microscope, DNA fragmentation analysis and flow cytometry. In the attempt to elucidate whether this compound might affect genes playing a role in G1/S phase transition, the expressions of p53, p21(WAF1), cyclin D1 and Rb, mainly involved in response to DNA-damaging stress, were analyzed by Western blot. Heterogeneous patterns of expression during exposure to IST-FS 29 were evidenced in the different cell lines suggesting that these cell-cycle-related genes are not likely the primary targets of this compound. Thus, the present data seem more indicative of a direct effect of IST-FS-29 on macromolecular synthesis and cellular homeostasis, as previously hypothesized for other organotin complexes.

Monoamine oxidase inhibitor properties of some benzazoles: structure-activity relationships.

Benzazoles containing two or three nitrogen atoms were screened for their inhibitory activity toward monoamine oxidases MAO-A and MAO-B. In order to clarify the mechanism of interaction of these compounds with the enzyme, their electronic structure was calculated at the ab initio level and the influence of lipophilicity on activity was investigated. The mode of binding of benzazoles to MAO-B appears different from that of previously investigated heterocycles.

Thiolupinine and some derivatives of pharmacological interest.

The (quinolizidin-1 alpha-yl)methanthiol (thiolupinine) was prepared and, utilizing the thiol group reactivity, several S-substituted derivatives were obtained among which was a group of 3-[(lupinylthio)methyl]indoles. Eight of the prepared compounds were subjected to a broad pharmacological screening that evidentiated for many of them good level of the following activities in vivo and in vitro: antiarrhythmic, local anesthetic, negative chronotropic on isolated atria, calcium antagonism on ileum and atria, inhibition of spontaneous contraction of isolated trachea, inhibition of guinea pig ileum contractions induced by angiotensin I and II, bradykinin and cholecystokinin, inhibition of platelet aggregation induced by PAF and ADP. Single compounds were remarkable for additional antagonistic activities: 4 against P1-purine receptor, 8 against substance P, 12 against methacholine and 13 strongly inhibited arachidonate induced platelet aggregation. Very peculiar was the ability of compound 6 to protect mice from PAF induced mortality.

2-(4-R-phenoxy/phenylthio)alkanoic esters of l-lupinine.

Considering the great pharmacological interest in phenoxy/phenylthioalkanoic esters of open-chain or cyclic aminoalcohols, a set of ten such esters of lupinine was prepared. Initially, their ability to displace [3H]QNB from rat brain preparation was investigated. With the exception of two, all the prepared esters exhibited good affinity to muscarinic receptors (on a non-selective basis), with pKi in the range 6.67-7.68.

Synthesis and preliminary pharmacological investigation of some 2-[4-(dialkylaminoalkoxy)phenyl]benzotriazoles and their N-oxides.

A set of 2-[4-(dialkylaminoalkoxy)phenyl]benzotriazoles and corresponding N-oxides was prepared. In a preliminary pharmacological investigation concerning some of these compounds, several in vitro and in vivo activities were shown. At concentrations in the range of 3-10 microM all tested compounds strongly inhibited (50-100%) the guinea pig ileum contractions induced either electrically or by means of several agonists; of particular interest was the antagonism to leukotriene D4. Compound 5b inhibited platelet aggregation induced by thromboxane A2, PAF and ADF (but not by arachidonic acid) and increased the bleeding time in mice. Compounds 5b and 6b protected mice from potassium cyanide hypoxia and exerted anti-hypercholesterolemic action; the first compound produced a ratio between HPL and total serum cholesterol concentrations below 0.92, thus indicating a potential anti-atherogenic activity.

Preparation and pharmacological activities of 10-homolupinanoyl-2-R-phenothiazines.

Pursuing our researches on quinolizidinyl derivatives of phenothiazine and on the ground of antidepressive, diuretic, antianginal and antiarrhythmic activities of several 10-(3-dialkylamino) propionylphenothiazines (as chloracizine, moricizine, etc.), six 10-homolupinanoyl-2-R-phenothiazines were prepared and subjected to a broad pharmacological screening with in vivo and in vitro assays. Most of these compounds exerted strong antiarrhythmic activity (compounds 1, 3 and 5 were comparable or superior to lidocaine and quinidine in three tests), calcium antagonism on guinea pig ileum and left atria, antagonism to smooth muscle contractile responses induced by several agents and inhibition of rabbit platelet aggregation induced by PAF and ADP. A few other activities were characteristic of single compounds, as antagonism to central and peripheral effects of oxotremorine 1, moderate antihypertensive activity 5, local anesthetic activity and antagonism to substance P 2, antiinflammatory activity with low or absent gastric irritation 2, 3, powerful saluretic action 6, inhibition of arachidonate induced platelet aggregation 1 and antagonism to PAF induced mortality 1, 4. The last activity is very unusual and deserves further investigation. The capacity of compound 1 to displace specific ligands from several receptors was also investigated. Significant binding for M1 (IC50 = 0.03 microM), M3 (IC50 = 10 microM), sigma receptors and Na+ channels (IC50 = 1 microM) were evidentiated.

Preparation and pharmacological activities of homolupinanoyl anilides.

On the pattern of well known dialkylaminoacyl anilides, a set of N-homolupinanoyl anilides was prepared and subjected to a broad pharmacological screening with in vivo and in vitro assays. As expected most compounds exhibited a strong antiarrhythmic activity, often comparable or superior to that of lidocaine and quinidine. Compound 1 exhibited an unusual profile as antiarrhythmic, being devoid of local anesthetic activity, calcium channel and beta adrenoceptor antagonism. Calcium channel blocking activity was seen in all aminobenzophenone derivatives, but not in the simpler anilides. Noteworthy are also the capacity of compound 7 to protect mice from a lethal dose of KCN, the moderate antihypertensive activity of 10 and, above all, the antagonism to guinea pig ileum contractile responses induced by several agents exhibited by compound 11, which deserves further investigation for a potential use in irritable bowel syndrome. Compound 11 showed also good relaxant activity on tracheal strips and inhibitory activity against arachidonate induced platelet aggregation. Finally, compound 11 displaced several radioligands from their respective binding sites. Most potent was displacement of [3H]pirenzepine (IC50 < or = 0.01 microM) from M1 binding sites of rat brain, while displacement of [3H] methylscopolamine from rat heart (M2) and submaxillary salivary glands (M3) preparations was much weaker (IC50 approximately equal to 2.4 and 1.3 microM, respectively).

7-(N-substituted)amino-2,3-polymethylene benzofurane derivatives with tracheal relaxant activity.

A set of twelve 7-(N-substituted)amino-2,3-polymethylenebenzofuranes (1-12) together with three related compounds (13-15) was prepared. Ten selected compounds were tested for tracheal relaxant activity in vitro and two of them (6,7) were also subjected to a broad pharmacological screening. Five compounds (2,7,9,12,14) at the concentration of 30 micrograms/ml exhibited high tracheal relaxant activity (73-94% tone reduction) that was superior than that of theophylline at the same concentration. The 7-(N-trifluoromethylsulfonyl)amino-2,3-tetramethylenebenzofuran e (9) was highly active till the concentration of 1 microgram/ml giving a stronger tracheal relaxation than amrinone at 3 micrograms/ml. On the other hand the general screening did not show any other major activity. The benzofurane derivatives 1-13 were obtained through obvious steps from the corresponding 7-nitrobenzofuranes, which were prepared by a Fischer indole-like cyclization of O-[(2-nitro)phenyl] ketone oximes. In one case two peculiar side products were isolated.

Preparation and pharmacological activities of spiro[3,4-dihydro-6/7-R-1,2,4-benzotriazine-3,4'-(1'-substituted)piperi dines].

A set of spiro[3,4-dihydro-1,2,4-benzotriazines-3,4'-piperidine] derivatives was prepared and subjected to a broad pharmacological screening. Many of these compounds are characterized by a 3-(4-fluorobenzoyl)propyl substituent on the piperidine nitrogen, thus resembling the p-fluorobutyrophenone antipsychotics. Modest dopamine antagonism was observed for the tested compounds, which however were mainly endowed with analgesic and antihypertensive activities. Antihypercholesterolemic activity was also seen in compound 5, which represents an interesting new lead, being completely structurally unrelated to the known agents in this field.

Synthesis and preliminary pharmacological evaluation of 3-[2-(1-aryl-piperazin-4-yl)ethyl]-3,4-dihydro-3-methyl-6-R-1,2, 4-benzotriazines.

A set of 3-[2-(1-aryl-piperazin-4-yl)ethyl]-3,4-dihydro-3-methyl-1,2, 4-benzotriazines, bearing different substituents on the aromatic nuclei, was prepared and found to be endowed with good antihypertensive activity. The simplest compound 1, subjected to a broad pharmacological screening, exhibited also analgesic and antiallergic activities and hints of hypocholesterolemic action. Moreover this compound inhibited (in vitro tests) the guinea pig ileum contractions induced by several agents, the rat vas deferens contractions induced by phenylphrine (alpha 1 antagonism), the platelet aggregation induced by arachidonate and the tracheal tone.

Quinolizidinyl derivatives of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid and 1-homolupinanoyl benzimidazolones as ligands for 5-HT3 and 5-HT4 receptors.

Five 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives of lupinine, epi-lupinine and lupinylamine, together with two 1-homolupinanoyl benzimidazolones were prepared and investigated for their ability to displace specific radioligands from 5-HT3 and 5-HT4 receptors. The synthesized compounds were only moderately active, with IC50 in the micromolar range. The compound with the highest affinity for 5-HT4 receptor was tested for the enhancement of intestinal transit rate but was inactive at the oral dose of 100 mg/kg.

Synthesis and biological investigations of 1-(tetrahydropyran-2'-yl)- and 1-(tetrahydrofuran-2'-yl)benzimidazoles and 1/2-(tetrahydropyran-2'-yl)- and 1/2-(tetrahydrofuran-2'-yl)benzotriazoles.

Sets of benzimidazole and benzotriazole derivatives bearing on position 1 or 2 a tetrahydrofuranyl or tetrahydropyranyl moieties were prepared through the addition of the suitable benzazoles on 2,3-dihydrofuran and 3,4-dihydro-2H-pyran. The reactions were carried on either without solvent or in carbon tetrachloride solution. In the last case some peculiar chlorinated side products were isolated and characterized. Twenty compounds were screened for in vitro antitumoral and anti-HIV-1 activities and found poorly active or completely inactive. On the other hand several compounds exhibited good tracheal relaxant activity in vitro; compound 8, 11, 16, 24 and 26 resulted more active than theophylline in this test, while compound 11 was comparable to amrinone till the concentration of 3 micrograms/ml. Finally, compound 5 resulted endowed with a strong diuretic and saluretic activity at the dose of 3 mg/Kg, thus representing a new lead for discovering new diuretic agents.

Synthesis and preliminary pharmacological evaluation of some cytisine derivatives.

Thirty-one N-derivatives of cytisine were prepared in order to modify its pharmacological profile and to obtain compounds of potential therapeutic interest either at a peripheral or central level, particularly as nicotinic ligands with improved ability to cross the blood-brain barrier. Actually, with the introduction of different kinds of substituent on the basic nitrogen of cytisine a variety of activities were observed, both in vivo (analgesic, dopamine antagonism, antihypertensive, inhibition of stress-induced ulcers, antiinflammatory, protection from PAF-induced mortality, hypoglycemic) and in vitro (positive cardio-inotropic, beta-adrenergic antagonism, alpha 1- and alpha 2-antagonism, inhibition of PAF-induced platelet aggregation). Six randomly selected compounds were tested for the ability to recognize a central nicotinic receptor and four of them exhibited Ki values in the range 30-163 nM.

Synthesis and pharmacological evaluation of some thiolupinine derivatives.

A small set of 9-(lupinylthio)xanthene, -thioxanthenes and alpha-(lupinylthio)diphenylmethanes was prepared and found to inhibit the angiotensin II-induced contractions of guinea pig ileum. Some of these compounds were also moderately active in vitro as tracheal relaxants and one compound was more active than aspirin against arachidonic acid-induced platelet aggregation.