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Biomedical subjects

A Fabbri

Publications and source records attributed to A Fabbri.

At least 109 records · Page 6Linked to original sources
PubMed1997

Escherichia coli cytotoxic necrotizing factor 1 (CNF1), a toxin that activates the Rho GTPase.

Cytotoxic necrotizing factor 1 (CNF1), a 110-kDa protein toxin from pathogenic Escherichia coli induces actin reorganization into stress fibers and retraction fibers in human epithelial cultured cells allowing them to spread. CNF1 is acting in the cytosol since microinjection of the toxin into HEp-2 cells mimics the effects of the externally applied CNF1. Incubation in vitro of CNF1 with recombinant small GTPases induces a modification of Rho (but not of Rac, Cdc42, Ras, or Rab6) as demonstrated by a discrete increase in the apparent molecular weight of the molecule. Preincubation of cells with CNF1 impairs the cytotoxic effects of Clostridium difficile toxin B, which inactivates Rho but not those of Clostridium sordellii LT toxin, which inhibits Ras and Rac. As shown for Rho-GTP, CNF1 activates, in a time- and dose-dependent manner, a cytoskeleton-associated phosphatidylinositol 4-phosphate 5-kinase. However, neither the phosphatidylinositol 4,5-bisphosphate (PIP2) nor the phosphatidylinositol 3,4-bisphosphate (PI 3,4-P2) or 3,4,5-trisphosphate (PIP3) cellular content were found increased in CNF1 treated HEp-2 cells. Cellular effects of CNF1 were not blocked by LY294002, a stable inhibitor of the phosphoinositide 3-kinase. Incubation of HEp-2 cells with CNF1 induces relocalization of myosin 2 in stress fibers but not in retraction fibers. Altogether, our data indicate that CNF1 is a toxin that selectively activates the Rho GTP-binding protein, thus inducing contractility and cell spreading.

Actins↗
PubMed1997

Glutathione kinetics in normal man and in patients with liver cirrhosis.

BACKGROUND/AIMS: The dynamics of glutathione in plasma has always been studied by bolus injections. Data are available suggesting that the low plasma levels of cirrhosis are due to decreased production in glutathione-producing tissues, mainly the liver. We aimed to measure the kinetics of glutathione during controlled steady-state conditions, and to determine the reasons for its reduced plasma levels in advanced cirrhosis. METHODS: The plasma clearance of glutathione was measured in six control subjects and in ten patients with cirrhosis during a 2-step infusion study, producing steady-state levels approximately 5 and 10 times basal values. The plasma disappearance curve after infusion stop was used to determine the apparent volume of distribution and half-life of glutathione, and the estimated basal appearance rate. RESULTS: The clearance of glutathione did not reject 1st-order kinetics, i.e., it was concentration-independent, and was nearly doubled in cirrhosis. The half-life of exogenous glutathione was not different, whereas the volume of distribution was larger in cirrhosis, in the same range as extracellular water. The endogenous basal appearance rate of glutathione was reduced by 50%, and correlated with liver function, measured by routine and dynamic tests. CONCLUSIONS: The data confirm that the primary defect responsible for reduced glutathione in liver disease is a reduced production, possibly related to hepatocyte dysfunction and a block along the pathway of methionine metabolism.

Adult↗
PubMed1997

Involvement of chromosome 6 in endometrial cancer.

Cytogenetic investigation was performed on direct preparations of 15 endometrial cancers showing different histotypes. Clonal abnormalities were found in 11 out of 13 analysable cases. The modal chromosome number was near diploid in all cases. The abnormal karyotypes contained relatively simple numerical or structural aberrations in the majority of tumours. In contrast, two neoplasms with serous papillary and mixed mullerian morphological features shared multiple complex changes as well as cytogenetic evidence of intratumoral heterogeneity. The most frequent chromosome abnormality in our series of endometrial neoplasms was 6q deletion, which was detected in serous papillary, endometrioid and mixed mullerian tumours. The loss of the 6q region, which is also frequently involved in ovarian carcinoma, suggests a relationship between endometrial and ovarian cancers based on a common histogenesis.

Adenocarcinoma↗
PubMed1997

Teicoplanin concentrations in serum, pericardium, pericardial fluid and thoracic wall fat in patients undergoing cardio-pulmonary bypass surgery.

The concentrations of teicoplanin in serum, pericardium, pericardial fluid and thoracic wall fat were measured in patients undergoing cardio-pulmonary bypass (CPB) after the administration of a single i.v. 12 mg/kg dose. Five minutes after the start of CPB, teicoplanin serum concentrations decreased by, on average, 35% (95% confidence interval (CI): 28-42%) and remained significantly lower than the expected values over the subsequent 60 min period. After aortic unclamping drug concentrations rebounded but remained significantly lower than the expected values in the next 60 min. Immediately before CPB, penetration of teicoplanin in pericardium and thoracic wall fat was 0.44 (95% CI: 0.23-0.65) and 0.05 (95% CI: 0.03-0.7), respectively, and increased at the end of CPB to 0.90 (95% CI: 0.55-1.25) and 0.17 (95% CI: 0.05-0.29), respectively. MICs for most staphylococcal strains were attained during CPB procedure in pericardium but not in thoracic wall fat. However, since staphylococcal infections involve the interstitial space it is likely that penetration into fat cells is not important for antimicrobial prophylaxis. In this respect, it is worth noting that drug concentration in pericardial fluid, which should reflect the interstitial concentration, was higher than the MIC for most staphylococcal strains. Although no infective complications were observed in our limited series of patients, larger clinical trials are needed to assess whether the dose regimen employed is effective in preventing post-CPB surgery infections.

Adipose Tissue↗
PubMed1997

Primary serous papillary adenocarcinoma of the vagina: a case report.

The first reported case of vaginal serous papillary adenocarcinoma (VSPA) in a 61-year-old woman is presented. The woman had a mass in the upper posterior vaginal wall that was 2.5 cm in maximal dimension and was treated with a radical hysterectomy with bilateral salpingo-oophorectomy, lymphadenectomy, and subtotal vaginectomy, followed by radiation therapy. The ovaries, fallopian tubes, cervix, endometrium, and peritoneum did not show primary or secondary neoplastic involvement. The patient died because of recurrent disease in the form of widespread peritoneal metastases 30 months postoperatively. Microscopically, the tumor was similar to serous papillary adenocarcinoma of the ovary (OSPA). Immunohistochemical studies showed positive staining for CA 125, CA19.9, DUPAN-2, and TAG-72, and negative staining for CEA. Cytogenetic analysis showed chromosome 6 abnormalities similar to those found in OSPA. These results suggest that VSPA is a clinically aggressive primary tumor sharing morphological and cytogenetic analogy with OSPA.

Adenocarcinoma, Papillary↗
PubMed1997

Cutaneous vasodilation to acetylcholine in patients with essential hypertension.

Endothelium-dependent vasodilation is reduced in the forearm of patients with essential hypertension. To evaluate whether endothelium-dependent vasodilation is also reduced in the skin microcirculation of patients with essential hypertension, we evaluated the effect of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, on cutaneous and total forearm blood flow in normotensive subjects (n = 8) and matched patients with essential hypertension (n = 9). We infused acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml forearm tissue/min) and sodium nitroprusside (1, 2, and 4 microg/100 ml forearm tissue/min) into the brachial artery, and we measured cutaneous blood flow (laser Doppler flowmeter) and muscle blood flow (strain-gauge venous plethysmography) modifications. Both the cutaneous and muscle blood flow increases induced by acetylcholine were reduced in patients with essential hypertension as compared with normotensive controls, whereas the skin and muscle vasodilation induced by sodium nitroprusside was similar in the two groups of patients. These data confirm the impairment of endothelium-dependent vasodilation in the muscle vascular bed of patients with essential hypertension and demonstrate the presence of endothelial dysfunction in skin microcirculation.

Acetylcholine↗
PubMed1997

Uncertainty in liver function assessment on the basis of single-point galactose concentration.

The uncertainty in liver function assessment based on single-sample galactose levels after galactose injection, in comparison to the standard procedure using the galactose elimination capacity (GEC), was assessed in 905 tests performed in a wide range of liver functions. The 45-min galactose levels significantly correlated with GEC, the correlation being better in subjects with a good liver function. In cirrhosis, the prediction using the 60-min galactose value was better than when the 45-min value was used. In the whole series, the 95% confidence interval of GEC predicted by 45-min galactose was as large as +/- 1.55mg x kg(-1) x min(-1) as absolute value, corresponding to a range from -41 to +47% of measured GEC. In cirrhosis, the 95% confidence interval was +/- 1.42 mg x kg(-1) x min(-1) and between -40 and +46% of measured GEC. The 60-min values were more predictive, but in Child class C patients the average error was 0.42 mg x kg(-1) x min(-1) (95% confidence interval -0.64 to +1.49, corresponding to -39 to +76% of measured GEC). The uncertainty was maintained within +/- 10% of measured values only in 50% of the tests. We conclude that the single-point galactose test introduces a considerable error, mainly in patients with more advanced liver disease, which may bias the decision-making process.

Analysis of Variance↗
PubMed1997

Amphotericin B treatment of fungemia due to unusual pathogens in neutropenic patients: report of two cases.

Invasive fungal infections occur frequently in neutropenic patients although only in recent years has the role of emerging fungi been clearly established. We describe two cases of fungemia caused by Trichosporon beigelii and Rhodotorula glutinis respectively in two neutropenic patients with hematological malignancies who were treated with amphotericin B. The first patient, with refractory multiple myeloma, died following massive pneumonia despite therapy with amphotericin B and granulocyte-colony stimulating factor (G-CSF); the second patient, with relapsed acute lymphatic leukemia and persistent fever without any other clinical evidence, finally recovered. Amphotericin B continues to be considered the "gold standard" in the treatment of invasive mycoses although other approaches need to be tested for refractory infections.

Adolescent↗
PubMed1997

[Replacement of the aortic valve with a pulmonary autograft: experience at the University of Verona].

BACKGROUND: Early and long term results after surgical replacement of the aortic valve depend to a large degree on the type of valve substitute used. Pulmonary autograft offers many theoretical advantages, particularly in young patients. METHODS: Between July 1994 and August 1996, 15 patients (12 male) with a mean age of 28 +/- 6 years (range 14 to 36 years) were selected for aortic valve replacement with a pulmonary autograft. The aortic valve disease was isolated insufficiency in 7 cases (47%), stenosis in 3 (20%) and mixed lesion in 5 (33%). One patient in the last group had bacterial endocarditis (Streptococcus mitis). Seven patients (47%) had a bicuspid aortic valve. In 3 cases (20%) the autograft was inserted as a scalloped subcoronary implant. Twelve patients (80%) had total aortic root replacement with re-implantation of the coronary ostia. The right ventricular outflow tract was reconstructed with a cryopreserved homograft (13 pulmonary; 2 aortic). The aortic cross-clamp time was 156 +/- 18 minutes with a total bypass time of 221 +/- 26 minutes. RESULTS: All patients survived the operation. Three postoperative bleeding (20%) necessitated re-exploration. Mean post-operative hospital stay was 10 +/- 2 days. All patients were discharged on aspirin for the period of three months. One patient (7%) with moderate neo-aortic valve insufficiency died suddenly 11 months post-operatively. All survivors are asymptomatic, in NYHA FC 1 at a mean follow-up time of 15.7 months. Freedom from reoperation, valve related complication and endocarditis is 100%. Two-dimensional (2-D) echocardiography six months postoperatively showed a mean left ventricular outflow gradient of 13 +/- 4 mmHg with no evidence of aortic regurgitation in 11 cases (78.5%) and trivial in 3 (21.5%). CONCLUSIONS: Although the Ross operation is technically more challenging and requires a longer operating time than standard procedures, this does not seem to affect early mortality and morbidity. Clinical and haemodynamic results appear to be gratifying. Continued patients evaluation particularly with regard to evidence of valve degeneration and arrhythmias in the long term is warranted.

Adolescent↗
PubMed1997

Current techniques to reduce blood loss after the Ross procedure.

BACKGROUND AND AIMS OF THE STUDY: Although pulmonary autograft (PA) offers many theoretical advantages, the operation is more complex and the need for extensive reconstruction carries an increased risk for postoperative bleeding. The study aim was to evaluate the impact of different pharmacological and surgical strategies on total blood loss and blood product requirements after PA use. METHODS: Between July 1994 and March 1997, 26 patients (22 males) with a mean age of 26 +/- 8 years (range: 11 to 36 years) underwent aortic valve replacement with PA (22 root; four subcoronary implant). A relatively high incidence of re-exploration for bleeding (n = 3) and significant total blood loss during our early experience (Group I, n = 8), prompted the subsequent introduction of different strategies (Group II, n = 18). These included perioperative use of aprotinin, reinforcement of suture lines of the neo-aortic root with autologous pericardium and accurate hemostasis of the raw surface on the back of the right ventricular outflow tract (RVOT) during a brief period of circulatory arrest, also with application of fibrin glue, RESULTS: There were no hospital deaths. No patients in group II required re-exploration or transfusion, and mean total postoperative blood loss was reduced (group I, 720 +/- 465 ml/m2 body surface area (BSA), versus group II, 323 +/- 84 ml/m2 BSA). By-pass and aortic cross-clamp times were not significantly longer in group II patients. At a mean follow up of 15 months, all 25 survivors are asymptomatic, in NYHA functional class I, and with normal social interactions. CONCLUSIONS: Early survival after aortic valve replacement with the PA appears comparable with the use of more conventional valve substitutes. Blood loss containment by routine application of medical and surgical strategies appears feasible. In view of the common concern about blood transfusion, particularly in young patients, these findings may help to widen the range of indications for the Ross procedure.

Adolescent↗
PubMed1997

[Postcoital contraception. Dates based on a 5-year use in a private consultation service].

BACKGROUND: The aim of this 5-year retrospective study is to define the efficacy of oestro-progestinic interception. METHODS: An oestro-progestinic mixture (0.05 mg ethinyl estradiol and 0.250 mg dlnorgestrel) was prescribed to 6003 women attending the gynaecological outpatients clinic of AIED (Associazione Italiana per l'Educazione Demografica) in Genoa, Italy, without evidence of any previous contra-indications. The prescription was of two pills at once and two pills 12 hours after. Before examination, the doctor asked for personal and medical history (age, date of onset of menses, unprotected intercourse date and anticonceptional failure); patients were also asked to report the data of the following menses to the clinic. The largest age range was between 20 and 24 years, probably because of their inadequate knowledge of contraceptives. The reasons for post-coital contraception were: sexual intercourse without contraceptive, failure of coitus interruptus and of the condom. RESULTS: Post-coital interception efficacy (monthly oestro-progestinic contraception was 99.5%) according to retrospective statistical analysis, was according to Pearl index 92.9% vs 50% without any contraceptive. CONCLUSIONS: Finally, the efficacy of this method, together with its easy management and low frequency of severe contra-indications, allows us to indicate the "morning after pill" as one of the most useful outpatient strategies to avoid unwanted pregnancies.

Adult↗
PubMed1996

Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis.

Zinc deficiency is common in cirrhosis and has been involved in the altered nitrogen metabolism. In this study, we measured the effects of zinc supplementation on the dynamics of amino acid-derived urea synthesis in cirrhosis with mild or latent encephalopathy. The hepatic conversion of amino acids into urea was studied in eight patients with advanced cirrhosis under controlled conditions of substrate availability (continuous alanine infusion), before and after 3-month oral zinc sulfate supplementation (600 mg/d). Eight more patients, matched for hepatocellular failure and encephalopathy, served as controls. Plasma zinc levels were reduced in all patients and returned to normal after oral zinc. The alanine-stimulated urea nitrogen synthesis rate in relation to alpha-amino-N concentration--the functional hepatic nitrogen clearance--increased by 25% after zinc supplementation, i.e., more urea was produced at any alpha-amino-N concentration. Basal and alanine-induced glucagon decreased by 50%, and the ammonia response to alanine decreased by 30%. Psychometric tests improved, as did routine and dynamic liver function tests and the Child-Pugh score. Also, the plasma concentration of lipid peroxides was reduced by zinc. No significant changes were observed in the control group. Our data indicate that long-term oral zinc speeds up the kinetics of urea formation from amino acids and ammonia. Changes in the hormonal drive and/or the antioxidant activity of zinc might be involved in the general improvement in liver function, whereas the beneficial effects on encephalopathy might stem from decreased ammonia.

Administration, Oral↗
PubMed1996

The course of galactose elimination capacity in patients with alcoholic cirrhosis: possible use as a surrogate marker for death.

There is increasing interest for the use of surrogate end points in the evaluation of treatments in patients with liver disease, but adequate validation is seldom available. This study aimed to describe the different course of galactose elimination capacity in patients with alcoholic cirrhosis who continued to drink or abstained from alcohol consumption during follow-up, and to validate changes in galactose elimination as a surrogate end point for death from liver-related causes. Forty-five patients with alcoholic cirrhosis (22 who continued drinking throughout the study period, and 23 who stopped drinking and were abstinent throughout the study period) were retrospectively selected among patients who had galactose elimination capacity measured at 6-month intervals. During follow-up 10 drinkers and 3 abstainers died of liver-related causes (P = .025). Abstainers showed a transient improvement in galactose elimination capacity, followed by a decrease. Continuous drinkers showed a reduction from the beginning. According to Cox's regression analyses, persistent alcohol abuse and galactose elimination capacity were separately related to the risk of death, but, when a time-dependent model was fitted containing galactose elimination capacity and persistent alcohol abuse, only the former remained significant. This implies that variations in the risk of death occurring as a consequence of abstinence from alcohol consumption may be predicted from changes in galactose elimination capacity, and that the mechanisms through which abstinence influences survival are strictly linked to the mechanisms responsible for the changes in the test. Because of the strict association of decrease in galactose elimination capacity and short survival, as proved in several series, this observation represents adherence to the criteria requested for adequacy of a surrogate end point. In conclusion, in alcoholic cirrhosis the decrease in galactose elimination capacity is an adequate surrogate end point for death from liver-related causes, which is worth testing in other conditions and in response to other treatments.

Alcoholism↗
PubMed1996

Anxiety-induced failure in erectile response to intracorporeal prostaglandin-E1 in non-organic male impotence: a new diagnostic approach.

Intracavernous injection (ICI) of prostaglandin-E1 (PGE1) is used widely as the first diagnostic test in the study of erectile dysfunction. However, a lack of full erection after a maximal dose is frequent. As well as vascular incompetence, this may be due to stress-induced changes, related to the ICI procedure. The aim of this study was to investigate the influence of emotional disturbances on erectile response to ICI in impotent patients. Initially, 24 young men with non-organic impotence (age 34.6 +/- 1.5 years; mean +/- SEM) were selected and randomized single-blind to pharmacoerection with PGE1 alone (20 micrograms/mL) or a mixture (cocktail) containing 20 micrograms PGE1 plus an alpha-adrenergic receptor blocker, phentolamine (Phe, 0.5 mg/mL). Additional studies were also performed double-blind on 10 men with non-organic impotence (age 37.6 +/- 1.2 years) utilizing higher PGE1 dosages for ICI (25 micrograms/mL alone or in combination with Phe, 0.5 mg/mL). After a 7-day interval, all subjects were crossed-over to receive the alternative treatment. The presence of emotional disturbances was assessed in all patients by the administration of rapid tests (Stai-X1 and Stai-X1r for state-anxiety before and after ICI, respectively; Stai-X2 for trait-anxiety; Zung-test for depression) at the first and at the remaining (Stai-X1 and Stai-X1r) ICI sessions. ICI with 20 and 25 micrograms/mL PGE1 led to a comparable percentage of patients who reported a valid-for-intromission (VFI) erection (63 and 60%, respectively). In contrast, use of the cocktails significantly increased the percentage of subjects with a VFI (87 and 90% of the total number of patients tested, respectively; p < 0.05). Moreover, a strong inverse correlation between state-anxiety scores (Stai-X1) and the erectile response to ICI with 20 and 25 micrograms PGE1 was found (r = -0.69, p < 0.001); such a correlation was not present in patients who underwent ICI with the cocktails. Two cases of prolonged erection occurred (one after 20 micrograms PGE1 and the other after 20 micrograms PGE1 plus Phe) which were reversed promptly by the intracavernous injection of metharaminol. It is concluded that the lack of a full erectile response after ICI with PGE1 can be related to the presence of a high 'state-anxiety' in the patients. In such patients, a VFI erectile response can be induced by the administration of a cocktail test-dose.

Adrenergic alpha-Antagonists↗
PubMed1996

Bacteroides fragilis enterotoxin induces cytoskeletal changes and surface blebbing in HT-29 cells.

Certain strains of the anaerobic bacterium Bacteroides fragilis are known to produce an enterotoxin of about 20 kDa which is able to induce a fluid response in ligated intestinal loops and a cytotoxic response in HT-29 cells. It presents protease activity, belonging to a family of metalloproteases termed metzincins. In order to investigate the mode of action of the enterotoxin in cultured cells, we performed a study with HT-29 cells, using both fluoresence and electron microscopy. Treated cells underwent morphological changes, mainly consisting of the retraction of the cell body and the formation of numerous blebs on the cell surface. The microfilament system was reorganized, the F-actin being condensed as a ring at the cell periphery, whereas other cell organelles appeared to be unaffected. All these changes, clearly visible after 3 h of exposure to the toxin, were reversed within 24 h of treatment. By inhibiting the protease activity of the toxin with specific metal chelators, the cytoskeletal effects were also prevented. Thus, B. fragilis enterotoxin appears to act on cells by reversibly modifying the actin cytoskeleton, an effect probably dependent on its proteolytic activity.

Bacterial Toxins↗