Biomedical subjects

M Simone

Publications and source records attributed to M Simone.

At least 19 recordsLinked to original sources

PubMed2006

Pharmacokinetics and metabolism in mice of IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III), a new oral c-seco-taxane derivative with antiangiogenic property effective on paclitaxel-resistant tumors.

IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III) is a new taxane, derived from 7,8-C-seco-10-deacetylbaccatin, selected for its ability to inhibit angiogenesis, mainly by acting on endothelial cell motility, and for its selective activity on class III beta-tubulin. In vivo, IDN 5390 shows activity against paclitaxel-sensitive and -resistant tumors when administered on a prolonged, continuous dosage schedule. We studied the pharmacokinetics and bioavailabilty of the drug in mice after single and repeated oral treatment. IDN 5390 was rapidly absorbed after oral administration, with good bioavailability (43%). After intravenous injection, it was extensively distributed in tissue, mainly the liver, kidney, and heart, with low but persistent levels in brain. The kinetics appear dose-dependent with a clearance of 2.6, 1.4, and 0.9 l/kg at, respectively, 60, 90, and 120 mg/kg, and a half-life 24, 36, and 54 min. After prolonged daily oral doses given for 2 weeks, we found that there was a decrease in drug availability; i.e., the area under the concentration-time curve value after p.o. daily administration on day 14 was 2-fold lower than that on day 1. Metabolism plays a major role in elimination of the drug, and at least 12 metabolites were identified in feces and urine. The percentage excreted as metabolites after an oral dose (42%) was higher than that after the i.v. dose (33%), suggesting a first-pass effect. Four metabolites were found in plasma at detectable levels; one of them, with restored taxane scaffold, is a species 3 times more potent than IDN 5390, possibly contributing to the observed anti-tumor activity.

Angiogenesis Inhibitors↗

PubMed2004

Resveratrol interference with the cell cycle protects human neuroblastoma SH-SY5Y cell from paclitaxel-induced apoptosis.

In previous studies we demonstrated that resveratrol acts in an antiapoptotic manner on the paclitaxel-treated human neuroblastoma (HN) SH-SY5Y cell line inhibiting the apoptotic pathways induced by the antineoplastic drug. In the present study we evaluated the antiapoptotic effect of resveratrol, studying its activity on cell cycle progression. We determined the mitotic index of cultures exposed to resveratrol and paclitaxel alone or in combination, the cell cycle distribution by flow cytometric analysis (FACS), and the modulation of some relevant cell cycle regulatory proteins. Resveratrol is able to induce S-phase cell arrest and this interference with the cell cycle is associated with an increase of cyclin E and cyclin A, a downregulation of cyclin D1, and no alteration in cyclin B1 and cdk 1 activation. The resveratrol-induced S-phase block prevents SH-SY5Y from entering into mitosis, the phase of the cell cycle in which paclitaxel exerts its activity, explaining the antiapoptotic effect of resveratrol.

Antineoplastic Agents, Phytogenic↗

PubMed2004

[Morbidity after stapled haemorrhoidectomy: long-term results about 140 patients and review of the literature].

AIM: The aim of this study was to determine the results and the complications of the treatment of hemorrhoids with circular stapler with a follow-up of 18 months, and to review the complications in the literature. METHODS: From April 1998 to August 1999, 140 patients (83 males and 57 females) with an average age of 43.8 years (range: 19-83 years) underwent haemorrhoidectomy using a circular stapler in three university hospital centers. The degree of hemorrhoids has been classified: three cases of degree II, 97 cases of degree III, and 40 cases of degree IV. All the patients were prospectively evaluated at two weeks, two and 18 months after surgery. RESULTS: The average length of the operation was 18 minutes (range: 8-60 minutes). Mean hospital stay was 36 hours (range: 8-72 hours). There was no intraoperative complication. There was no mortality. The postoperative complication rate was 7.8% (N = 11): there were five cases of bleeding that two complicated by a submucosal hematoma (one was infected and needed a rectotomy on day 21), two cases of urinary retention, and two cases of external hemorrhoid thrombosis. The bleeding occurred in the 12 hours after surgery except for one patient with antivitamin K whith presented a secondary bleeding on day 16. At 18 months, five patients presented a moderate asymptomatic stricture dilated on digital examination. Two patients complained of persistent skin tags. Neither functional trouble nor incontinence to gas, liquids, or solids was presented. With a mean follow-up of 40 months, 90% (N = 112) of the patients were fully satisfied. CONCLUSIONS: Treatment of hemorrhoids with circular stapler appears to be effective with 96% of patients fully satisfied at 18 months. The morbidity rate was low, and no higher than the diathermy excision hemorrhoidectomy. The results are directly dependent on the practice that required a learning, and not on the technique itself.

Adult↗

PubMed2004

New drugs from the sea.

This paper illustrates some biochemical and pharmacological properties of two natural marine products such as trabectedin (ET-743, Yondelis) and aplidine. Trabectedin has shown clinical antitumor activity in refractory soft tissue sarcoma and ovarian cancer. The lack of cross resistance of trabectedin with other chemotherapeutic drugs is presumably related to its peculiar mode of action, that seems to be related to a promoter-dependent transcription modulation. Aplidine is a potent pro-apoptotic inducer in human leukemia and has antiangiogenic properties. These examples support the view that more research should be carried out to investigate new natural marine products since there are compounds among them with antitumor properties. Some of them appear to act by mechanisms different from those of conventional chemotherapeutic drugs and thus may be effective against tumors for which no active drugs are available.

Animals↗

PubMed2004

[The Bochdalek hernia in the adult: case report and review of the literature].

The Bochdalek hernia, the most common diaphragmatic hernia, except the hiatus hernia, is located on the posterolateral side of this muscle. This pathology is generally diagnosed in children; in fact only 105 such cases occurring in adults have been described in the literature. In these cases, surgical intervention is made necessary by the severity of potential complications. The Author's attention was drawn to a woman of 60 years of age, affected by pituitary nanism, who suffered from a left hand Bochdalek hernia. The symptomatology, characterised by abdominal pains and constipation had been presented for about one year. The computerised tomography confirmed the hernia of abdominal viscera in the thorax cavity. The intervention was conduced via the abdomen: the hernia were reduced, the hernial hole were closed with a double strata and the muscular plane reinforced with a synthetic prosthesis (dual mesh). The postoperative process was regular and the patient dismissed on 11th postoperative day.

Female↗

PubMed2003

Metabolic profile in patients with benign prostate hyperplasia or prostate cancer and normal glucose tolerance.

Familial predisposition together with several environmental factors may be involved in the pathogenesis of common prostate disease such as benign hypertrophy or prostate neoplasm. A higher incidence of both these conditions has been described in some insulin-resistant states such as obesity, but not much information is available on the effect of metabolic profile on gland morphology. The aim of this study was to evaluate the relation between glucose and lipid pattern and prostate diameters in two groups of non-diabetic individuals with benign prostate hypertrophy or cancer. 109 patients were recruited; plasma glucose, lipids and hormonal profile as well as an ultrasonographic evaluation of the gland volume and diameters were determined. Patients with prostate cancer had significantly higher levels of insulin and were more insulin resistant; in contrast, in subjects with prostate hypertrophy, fasting plasma glucose and--to a lesser extent--serum triglycerides emerged as the main determinants of gland volume. These observations may indicate that an improvement of insulin sensitivity and strategies to maintain a strict glucose and lipid control even in non-diabetic subjects are useful objectives in the prevention of prostate diseases.

Aged↗

PubMed2003

[Inflammatory tumors of the cecum in emergencies: surgical considerations and case report].

A cecal mass of uncertain etiology encountered during surgery for presumed appendicitis is a dilemma for the surgeon. The differential diagnosis of an unsuspected ileocecal mass must include neoplasm, diverticular disease, inflammatory bowel disease and severe appendicitis involving the ileocecal region. Right hemicolectomy is the gold standard for the treatment of the unsuspected ileocecal mass. The Authors report a case of inflammatory tumour of caecum secondary to appendicitis in a young adult.

Acute Disease↗

PubMed2002

[Principles of surgical technique of the anterior access to the thoraco-lumbar spine].

General surgeons are more and more frequently requested to prepare an operative exposure of the spine, in order to perform anterior maneuvers of removal and stabilization of the vertebral bodies. Since 1989 to date, in collaboration with the neurosurgical équipe of Prof. G. Cantore, Neurological Sciences Department, La Sapienza University of Rome, the Authors have collected 116 cases of vertebral diseases: among them, 48 involved the thoraco-lumbar junction of the spine (D12-L2). In this paper, Authors' aim is to state precisely the surgical technique of the anterior access to the thoraco-lumbar junction: attention has been focused on this tract of the column stating its anatomical complexity and the high invasivity of the procedures requested for its exposure. Therefore, such notes of technique have been elaborated to make safer the neurosurgical demolitive and reconstructive procedures and, most of all, to reduce the surgical trauma whenever it is possible.

Adolescent↗

PubMed2001

Treatment of hemorrhoids with circular stapler, a new alternative to conventional methods: a prospective study of 140 patients.

BACKGROUND: Surgical hemorrhoidectomy has a reputation for being a painful procedure. The aim of this study was to determine the efficacy and safety of a new procedure for surgical treatment of hemorrhoid disease. STUDY DESIGN: From April 1998 to August 1998, 140 patients (83 men and 57 women) with an average age of 43.8 years (range 19 to 83 years) underwent hemorrhoidectomy using a circular stapler. Operative times, pen- and postoperative complications, mean hospital stay, assessment of the postoperative pain, period of incapacity for work, and functional results were collected. All patients were evaluated at 2 weeks, 2 months, and 18 months after operation. RESULTS: The average length of the operation was 18 minutes (range 8 to 60 minutes). There were no perioperative complications. The postoperative complication rate was 6.4% (n = 9). Mean hospital stay was 36 hours (range 8 to 72 hours). Paracetamol was the only analgesic used. Eighty-three patients (59.3%) required analgesic for less than 2 days, 45 patients (32.1%) between 2 and 7 days, and 12 patients (8.6%) more than 7 days. No patients had anal wound care. One hundred four patients had professions. The period of incapacity for work was less than 3 days for 22 patients (21.1%), between 3 and 7 days for 13 patients (12.5%), between 7 and 14 days for 62 patients (59.6%), and more than 14 days for 7 patients (6.8%). At 18 months, 95.7% of patients were fully satisfied with the results, 3.6% were somewhat satisfied (n = 4), and 0.7% were unsatisfied. CONCLUSIONS: Treatment of hemorrhoids with a circular stapler appears to be safe, effective, and rapid, causing few postoperative complications and minimal postoperative pain. At 18 months, 95.7% of the patients were fully satisfied with the results.

Adult↗

PubMed2001

The carboxy-terminus of VirE2 from Agrobacterium tumefaciens is required for its transport to host cells by the virB-encoded type IV transport system.

Agrobacterium tumefaciens transfers DNA from the resident 'tumour-inducing' (Ti) plasmid into plant cells, where it can be stably integrated into the plant genome, ultimately resulting in crown gall tumour formation. The mobilized DNA molecule is a single-stranded intermediate with VirD2 covalently bound to its 5' end. Successful transport of the transferred DNA (T-DNA) and integration of the DNA into the genome requires that additional proteins be transported to the plant as well, including the single-stranded (ss)DNA-binding protein, VirE2. The transport of these two different substrates occurs as a result of the activities of a type IV secretion system encoded by the virB operon. Although the substrates have been identified, the mechanism of their transport remains unknown. In the experiments described here, a region in one of these substrates, VirE2, necessary for transport is identified. The addition of a C-terminal FLAG epitope tag to VirE2, or the deletion of its C-terminal 18 amino acids, renders it non-functional in A. tumefaciens. However, transgenic plants expressing either of these virE2 genes respond to virE2 mutants of A. tumefaciens by forming wild-type tumours. These results indicate that this region of VirE2 is necessary for the protein to be transported into the plant cells, but is not necessary for its function within the plant. Additionally, these studies demonstrate that mutant forms of VirE2 lacking this region do not disrupt the activities of the VirB transporter and support the hypothesis that VirE2 and the VirD2 T-strand are transported independently, even when they co-exist in the same cell.

Agrobacterium tumefaciens↗

PubMed2000

[NMR cholangiography in the diagnostic algorithm of candidates to video laparocholecystectomy].

BACKGROUND: High resolution magnetic resonance cholangiopancreatography (MRCP) is a non invasive imaging modality for depicting the pancreatobiliary tree. It can demonstrate dilation, stenosis and intraductal filling defects of both the biliary and the pancreatic duct. The imaging quality of high resolution MRCP is excellent. MRCP appears to be more effective and less invasive than endoscopic retrograde cholangiopancreatography (ERCP) to evaluate many pancreatic and biliary diseases as choledocholithiasis, malignant obstruction, incomplete or failed ERCP, postsurgical alterations of the biliary tract (as biliary-enteric anastomoses), sclerosing cholangitis, chronic pancreatitis, and congenital anomalies of the biliary and pancreatic duct. METHODS: MRCP was performed in 21 non selected patients with suspected choledocholithiasis and demonstrated the presence of stones in the biliary tract in 5 of them. In these 5 patients sequential endoscopic-laparoscopic treatment was performed and confirmed in all cases the presence of stones in the biliary tree. Laparoscopic cholecystectomy (VLC) and transcystic cholangiography was attempted in the restant 16 patients. RESULTS: Laparoscopic transcystic cholangiography confirmed in all cases the response of MRCP. CONCLUSIONS: MRCP has the potential to replace ERCP in the management of patients candidate to VLC with suspected choledocholithiasis.

Algorithms↗

PubMed1999

T-cell activity in HLA-associated autoimmune diseases.

BACKGROUND: The existence of T-helper-1 (Th1) and T-helper-2 (Th2) subsets has been implicated in the regulation of several immune responses, and alterations in the Th1/Th2 balance have been involved in autoimmunity. The present study investigates the relative influence of Th1 and Th2 patterns in autoimmune responses in patients with HLA-associated autoimmune diseases. METHODS: This study concerns 849 patients of both sexes, suffering from several autoimmune diseases. Tissue typing for HLA antigens of Class I (A, B, C) and Class II (DR, DQ) was carried out in all patients by conventional serologic methods, comparing results with frequencies detected in a normal population. Many immunological tests were also done. In particular, lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg + B cells) were detected with monoclonal antibodies by a fluorescent cytometer. The changes in frequencies of T cell subsets were used to calculate the possible incidence of two effector phenotypes (TE-1; TE-2). RESULTS: The results of the immunogenetic analysis confirmed the significant HLA-associations in several diseases. The essential T-cell changes were also exposed, thus defining the incidence of T-cell phenotypes (TE-1 = 56.3%; TE-2 = 34.8%). This finding suggested a major impact of cell-mediated immunity, as compared with that of antibody-mediated immunity. CONCLUSIONS: The anomalies of Th1/Th2 balance can impact autoimmune disease, and in many cases a Th2 response can prevent Th1-mediated autoimmunity, which is the most evident phenomenon in several HLA-associated diseases.

Autoimmune Diseases↗

PubMed1999

Cytotoxic effector function in HLA-associated autoimmune diseases.

BACKGROUND: The mechanisms by which cytotoxic-T-lymphocytes (CTLs) and natural killer (NK) cells recognize and kill target cells are the subject of intense research. Previous observations in patients with HLA-associated autoimmune diseases show a major impact of cell-mediated immunity as compared to antibody-mediated immunity. This study analyzes the possible co-operation of NK cells in the autoimmune process, comparing their increase to that of cytotoxic-T-lymphocytes. METHODS: This research examines the incidence of CD8+ T cells and NK cells increases in 1065 patients with various autoimmune diseases. Tissue typing for HLA antigens was carried out in all patients by conventional serologic methods. Lymphocyte subsets (CD4+, CD8+, CD3-HLA-DR+, NK cells, sIg+ B cells) were detected with monoclonal antibodies by a fluorescent cytometer. Results were statistically compared to normal control values by the Student's "t"-test. RESULTS: The analysis of results shows the incidence of CTLs and NK cell increases in patients with different autoimmune syndromes. In some diseases (uveitis, multiple sclerosis, and other neurological autoimmune disorders) raised frequencies of NK cell increase are most evident. These results suggest some possible relationships between CTLs and NK cells in the pathogenesis of the autoimmune process. CONCLUSIONS: The present results show that CTLs and NK cells are implicated in immune dysregulation, which characterizes the complex pathogenesis of autoimmune diseases.

Autoimmune Diseases↗

PubMed1999

Immunogenetics of inflammatory bowel disease.

BACKGROUND: This study investigates the association of HLA antigens to inflammatory bowel disease (IBD), which is reminiscent of the simultaneous or subsequent presence of ulcerative colitis (UC) and Crohn's disease (CD) found in these patients, showing also the concomitant association of other autoimmune conditions. The aim of this study is to confirm the autoimmune origin of IBD and the immunogenetic basis of the disease. METHODS: The study concerns 18 consecutive patients of both sexes, aged 20 to 62 years, sharing the clinical criteria of IBD indicated by previous authors. Tissue typing for HLA antigens of Class I (A; B; C); and Class II (DR; DQ) was carried out by conventional serologic methods, comparing alleles frequencies with those of normal controls random selected by the chi-square test. The main immune functions and other laboratory tests were also done in all patients, to define the concomitant autoimmune condition. RESULTS: Immunogenetic analysis shows the significant increase in two HLA antigens: HLA-DR2 (50.0% vs 25.5% of controls); HLA-DR7 (44.4% vs 21.1% of controls). In particular, the association of HLA-DR7 to IBD is reminiscent of that found in a personal series of 54 patients with primary celiac disease (55.5% vs 21.1% of controls). The findings on immune functions show the high frequency of anomalies of cell-mediated immunity (62.5%) and humoral immunity (88.8%), associated with decrease in complement and increase in immune-complexes. These alterations were always correlated with the presence of HLA-DR2 and/or HLA-DR7. CONCLUSIONS: This study on immunogenetics of ibd does not separate UC and CD on genetic grounds, thus suggesting that common HLA Class II genes may predispose to an altered regulation of immunologic mechanisms in these disorders.

Journal Article↗

PubMed1996

Treatment of haemorrhage following rupture of aortic leiomyosarcoma. Survival for 4.2 years.

This paper describes a case of hemorrhage from an aortic leiomyosarcoma in which the patient exceptionally survived for 4.2 years after surgery. The operation consisted of resection of the aortic tract involved by the tumour and graft of a prosthesis. The diagnosis of aortic leiomyosarcoma had been based on the histological analysis and confirmed by histochemical and immunohistochemical findings.

Aged↗

PubMed1992

[Preliminary experience with the Storz Modulith SL 20 lithotriptor in reno-ureteral lithiasis].

The authors report their initial results in ESWL of urinary calculi with the Storz Modulith SL 20 lithotriptor, a multipurpose device for both urinary and biliary stone treatment. During 176 sessions, a total of 144 cases (81 renal and 63 ureteral) were treated and then, followed up. The over-all rate free of stones was 86.8% (90.1% for kidney and for ureteral stones). The treatment rate was 1.23 per patient. Auxiliary procedures before ESWL were performed in 7.9% of the sessions: insertion of "double-J" stent or nephrostomy tube; all ureteral stones received "in situ" treatment. Mean number of shock waves per session was 1836.1 (range 300-3020). The maximum voltage on the average reached was 17.1 kv. Sedo-analgesia by Diazepam and Ketoprofen was given in 75% of the cases. No serious complications were observed. The experience with this machine is discussed in regard to performance; the advantages of its fluoroscopy and ultrasound guided system of focusing are stressed.

Adolescent↗

PubMed1991

Sleep and benign partial epilepsies of childhood: EEG and evoked potentials study.

The electroclinical picture and nosological limits of benign partial epilepsy of childhood with rolandic spikes (BERS) have been better defined by nocturnal sleep records. In all stages of sleep, there is a significant increase in frequency and amplitude of rolandic spikes (RS) without change of their morphology. Another interesting observation is the appearance of independent spike foci in sleep, or brief subclinical spike wave discharges which are limited to the state of drowsiness. More recently, other types of partial epilepsy of childhood with benign evolution have been identified: (a) partial epilepsy with induced spike representing somatosensory evoked potentials; (b) benign psychomotor epilepsy; (c) partial epilepsy with occipital spike waves. In all these forms, the sleep records are essentially similar to those in BERS and have been very helpful in the nosological identification of these forms of epilepsy. For this reason, the sleep records of these special forms are truly informative for the clinician from the diagnostic and prognostic viewpoint. On the other hand, some investigators, have pointed out that, in the initial stage of these benign forms of partial epilepsy, there may be more or less significant intellectual impairment and behavioral disorder, sometimes accompanied by frequent brief absences. From the EEG viewpoint, this condition is characterized by brief discharges of slow spike wave complexes amounting to a pattern of "electrical status epilepticus". This special electroclinical condition mimics the Lennox-Gastaut syndrome but is generally self-limited. Thus, a correct differential diagnosis is very important from the diagnostic viewpoint. There is good evidence that sleep records permit an earlier identification of these conditions and strongly contribute to a correct differential diagnosis. In the benign partial epilepsy the SEPs, during awake and sleep, morphology and latency are normal, while the N60 amplitude is increased. A group of children with benign partial epilepsy shows EEG spikes evoked by tapping, and giant N60 component. This giant component persists during sleep and is not specific for any type of benign partial epilepsy. In conclusion, the results of sleep recordings are conducive to a correct diagnosis and better definition of the nosological delineation of partial epilepsies in childhood; they also provide a better comprehension of their evolution, and thus of their prognosis. The Evoked Potentials seem be a useful tool in the study of benign partial epilepsy.

Adolescent↗

PubMed1990

[Diagnostic screening of varicocele: role of echography and Doppler examination in our experience with 216 cases of primary varicocele].

We compared two non-invasive methods to evaluate primary varicoceles: ultrasonography and Doppler examination. We submitted to ultrasonography and Doppler 216 patients, 147 of them were treated by sclerotherapy and 69 by surgery. All ultrasonographic studies were performed by means of a real-time equipment (7.5 Mhz transducer), while Doppler examination was performed with continuous wave equipment. Ultrasonographic findings are reliable for testicular morphology. Doppler examination is useful to evaluate reversed flow. In 4.1% of cases ultrasonography did not agree with the Doppler examination.

Humans↗