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Biomedical subjects

F Franchi

Publications and source records attributed to F Franchi.

At least 19 recordsLinked to original sources

Failure of imaging techniques in revealing breast cancer progression.

This study focuses on a case of a 67-year-old woman with occult breast cancer involving the axillary lymph nodes. The instrumental examinations employed, positron emission tomography included, were not useful in diagnosing the disease. When the patient was surgically treated micro-invasive breast cancer was diagnosed. This peculiar malignant pathology is a matter of discussion especially because it is hardly diagnosable. Because of such diagnostic difficulties it may happen that micro-invasive carcinoma progression can easily mislead routine diagnostic screenings performed on women over 50.

Aged↗

Port site metastasis after laparoscopy for uterine cervical carcinoma.

BACKGROUND: Aim of this study was to review cases reported of port-site recurrence (PSR) after laparoscopy for uterine cervical carcinoma. METHODS: A Medline computer database search from January 1980 to September 2002. RESULTS: We reported 13 cases published of PSR after laparoscopy for cervical carcinoma. The majority of them were squamous carcinoma (9/13 at least, 69%) and initial staging of disease was Ib (7/13 (54%)). Median of interval between laparoscopy and diagnostic of PSR was 7 months (min 1.5 month, max 48 months). Of 10 cases of laparoscopy with lymphadenectomy, in three cases (30%) nodes were not involved. PSR developed at the port through which tissues was extracted in four cases (30.1%) or another port in five cases (38.5%). At the time of PSR, five patients (38.5%) were free of disease. CONCLUSIONS: PSR were reported after laparoscopy for lymphadenenectomy with or without hysterectomy and with or without node involvement. In some cases, umbilical metastases should not be systematically diagnosed as PSR and a diagnosis of Sister Mary Joseph's nodule may be discussed.

Adenocarcinoma↗

Val34Leu factor XIII polymorphism in Italian patients with inflammatory bowel disease.

BACKGROUND: Coagulation Factor XIII is implicated in fibrin stabilization and wound healing. Plasma levels of Factor XIII are reduced in inflammatory bowel disease patients; recently, a valine 34 to leucine polymorphism of the Factor XIII-A subunit gene with a defined protective effect against thrombosis and as yet undetermined effect on wound healing has been described. AIM: To evaluate Val34Leu Factor XIII polymorphism distribution and to find possible correlations with clinical features in Italian inflammatory bowel disease patients. STUDY POPULATION: A total of 152 inflammatory bowel disease patients, 90 with ulcerative colitis and 62 with Crohn's disease and 130 healthy volunteers were studied. METHODS: Val34Leu polymorphism was detected by RFLP with BsaH I. Statistical analysis was performed by means of Fisher exact test. RESULTS: In inflammatory bowel disease, 57.2% of patients showed the wild type status, 37.5% were heterozygous and 5.3% were homozygous for the 34Leu allele; the frequency of the mutated allele was 24.0%. In controls, 66.1% of subjects showed the wild type status, 28.5% were heterozygous and 5.4% were homozygous for the 34Leu allele; the frequency of the mutated allele was 19.7%. There was no difference in genotype distribution and prevalence of the mutated allele between inflammatory bowel disease patients and controls. CONCLUSIONS: The present data do not show any differences in Val34Leu Factor XIII polymorphism distribution between inflammatory bowel disease patients and controls. The prothrombotic state described in inflammatory bowel disease patients does not depend on an altered distribution of Val34Leu Factor XIII polymorphism.

Adult↗

The surgeon's decision as a prognostic factor in a pool of patients with colorectal cancer coming from different institutions.

Different pathological and predictive factors are used to stratify patients submitted to radical surgery for colorectal carcinoma. In addition to stage and histotype, the surgeon's technique and decisions also appeared to affect the prognosis. The aim of the present study was to evaluate if the extent of lymphadenectomy was associated with a different long-term outcome in a pool of 117 patients. In particular, in patients classified as Dukes' B, some evidences seem to suggest that the staging procedure depends on a correct surgical lymphadenectomy with a higher risk of understaging colorectal carcinomas when the number of removed nodes is limited. Moreover, the promptness in forwarding patients to the chemotherapist seems to influence the disease-free survival.

Colorectal Neoplasms↗

Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.

Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.

Adult↗

Systemic acute-phase response after laparoscopic and open cholecystectomy.

BACKGROUND: Cytokines are the main mediators of inflammation and the response to trauma. The purpose of this study was to compare variations in cytokine levels following laparoscopic cholecystectomy (LC) and mini-laparotomy cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. METHODS: A total of 40 patients were studied. Eighteen of them underwent LC; the remaining 22 were operated on using the open technique. Systemic concentrations of interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor (TNF), and C-reactive protein (CRP) were measured before and after the operation. In addition, we compared pre- and postoperative white blood cell (WBC) counts, postoperative body temperature, and length of postoperative hospitalization. RESULTS: There was no difference between the two groups in IL-1 and TNF response. The rise in plasma IL-6 levels (18.86 +/- 9.61 vs 5.00 +/- 0.0 pg/ml, p < 0.0001) and CRP (8.40 +/- 5.81 vs 1.43 +/- 1.30 mg/dl, p < 0.001) were more marked after open cholecystectomy than after the laparoscopic procedure. There was no correlation between serum CRP concentrations and the other postoperative parameters. CONCLUSION: The magnitude of the acute-phase response was less pronounced following laparoscopic cholecystectomy, consistent with a reduction in tissue trauma.

Acute-Phase Reaction↗

Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells.

Endothelin-1 (ET-1) is a vasoconstrictor peptide known to be a potent mitogen for glomerular mesangial cells (GMC). In the current study, it is demonstrated that ET-1 treatment of GMC results in serine phosphorylation of the 66-kDa isoform of the adapter protein Shc (p66(Shc)). ET-1-induced serine phosphorylation of p66(Shc) requires activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling module and is efficiently inhibited by both a MAPK/ERK kinase (MEK)-selective inhibitor and adenovirus-mediated transfer of a dominant interfering MEK1 mutant. Furthermore, adenovirus-mediated transfer of a constitutively active MEK1 mutant was found to markedly increase p66(Shc) serine phosphorylation. Adenoviruses encoding constitutively active mutants of MAPK kinases 3 and 6 (upstream kinases of p38(MAPK)) and 7 (upstream kinase of c-Jun NH(2)-terminal kinase) failed to induce serine phosphorylation of this adaptor protein. Serine phosphorylation of p66(Shc) resulted in its association with the serine binding motif-containing protein 14-3-3. ET-1-induced phosphorylation of a serine encompassed in the 14-3-3 binding motif of p66(Shc) was confirmed in experiments employing anti-phospho-14-3-3 binding motif antibodies. These studies are the first to demonstrate that G protein-coupled receptors stimulate serine phosphorylation of p66(Shc) and the first to report the formation of a signaling complex between p66(Shc) and 14-3-3.

14-3-3 Proteins↗

Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss.

Late fetal loss can be associated with placental insufficiency and coagulation defects. Thrombomodulin (TM) and the endothelial protein C receptor (EPCR) are glycoprotein receptors expressed mainly on the endothelial surface of blood vessels and also in the placenta; they both play a key physiological role in the protein C anticoagulant pathway. Defects in these proteins might play an important role in the pathogenesis of late fetal loss. We performed a case-control study in 95 women with unexplained late fetal loss (> 20 weeks), to elucidate whether TM or EPCR gene mutations were associated with an increased risk for this complication of pregnancy. The control group comprised 236 women who gave birth to at least one healthy baby and had no history of late fetal death or obstetrical complications. The entire TM and EPCR genes, including the promoter region, were screened. In total, five mutations were identified in the TM gene in 95 patients and three in 236 control subjects, and two mutations were identified in the EPCR gene in 95 patients and one in 236 control subjects. The relative risk for late fetal loss when having a mutation in the TM or EPCR gene was estimated by an odds ratio of 4.0 (95% CI 1.1-14.9). In conclusion, identified mutations in the TM and EPCR genes of women with unexplained fetal loss are more prevalent compared with women with no obstetrical complications.

Abortion, Habitual↗

Cardiovascular function in pregnancy: effects of posture.

OBJECTIVE: To evaluate the cardiovascular response to active postural changes in pregnancy. DESIGN: Prospective study. SETTING: Outpatient Clinic, Fetal Maternity Unit. PARTICIPANTS: Sixteen healthy women referred prior to pregnancy. METHODS: Heart rate, arterial pressure, echocardiographic end-diastolic and end-systolic left ventricular volumes (Teichholz' s formula) were measured in the three months before pregnancy, at the end of the first and second trimester, at mid third trimester, and six months after delivery in the supine and standing position, in thirteen women (mean age 33, range 25-38 years). RESULTS: Cardiac output (supine position) significantly increased (28%): it reached its maximum at the second trimester, remained steadily elevated in the mid third trimester, and returned to baseline after delivery. Cardiac output increased during pregnancy also in the active orthostatic position, the percentage increase being greater (70%) since the standing pre-conception value was lower. The postural stress induced similar changes in heart rate, arterial pressure and left ventricular ejection fraction before, during and after pregnancy. However, the reduction in cardiac output associated with early standing attenuated significantly at the second trimester and it was absent at mid third trimester (F = 3.13, P = 0.021). This was due to the interplay between the significantly lesser increase in systemic vascular resistance, occurring since the first trimester, and the significantly lesser decrease in left ventricular end-diastolic volume which was observed in the mid third trimester. CONCLUSION: These data indicate that the elevated cardiac output is adequately maintained in pregnancy during the postural challenge, due to optimisation of the responses of preload and afterload.

Adult↗

Activity of a nitroxylated analog of daunorubicin, ruboxyl, in B-lymphoproliferative disorders.

A nitroxylated analog of daunorubicin, ruboxyl (RBX), showed low toxicity but significant lympholytic effect in preclinical evaluations. A series of studies in vitro and in animals demonstrate that RBX is a putative agent in the treatment of many neoplasms. We report the results of a study in mice in which RBX showed selective B-lymphocyte immunosuppression. On the basis of this experience, RBX was administered to 3 patients with multiple myeloma and two patients with Waldenström's disease. The results of this pilot clinical study show that this compound has good activity and low myelotoxicity and cardiotoxicity, but seems to be characterized by a threatening immunosuppressive effect.

Aged↗

In vitro models of a three-drug regimen (epirubicin, cisplatin and fluorouracil) for the treatment of colorectal cancer.

The activity of epirubicin, cisplatin and 5-fluorouracil (5-FU), as single agents or in combination (ECF), was investigated in three human colon cancer cell lines by two different assays (cell-counting assay and sulforhodamine B assay) in vitro. 5-FU was tested with both short and continuous exposure. Particular interest was focused on the results obtained in the HCT8-FU cell line, a subline with experimentally induced resistance to 5-FU. The positive modulation of both cisplatin and epirubicin cytotoxicity by 5-FU makes the ECF regimen an attractive protocol for combination therapy in colorectal cancer.

Adenocarcinoma↗

Epirubicin, cisplatin and continuous-infusion 5-fluorouracil (ECF regimen) in the treatment of advanced colorectal cancer.

Thirty-one patients with advanced colorectal cancer were treated with a regimen of epirubicin, cisplatin and continuous-infusion (c.i.) 5-fluorouracil (5-FU) (ECF regimen). Twenty-seven patients were evaluable for response rate (RR), progression-free survival (PFS) and overall survival (OS). In this study, the ECF chemotherapy yielded a 51% RR with a PFS of more than 8 months, an OS of more than 11 months and tolerable toxicity. In spite of the perplexity concerning the use of anthracyclines in colorectal cancer, the ECF regimen seems to be a possible treatment even for this malignancy. Controlled studies with ECF versus standard treatments and versus 5-FU alone in c.i. are necessary.

Adult↗

Centrally mediated effects of bromocriptine on cardiac sympathovagal balance.

Bromocriptine, a dopamine agonist, is known to lower cardiovascular mortality in L-dopa-treated patients with Parkinson's disease, probably by reducing the cardiac sympathetic activity. We aimed at unmasking the central effects of bromocriptine on the heart by power spectrum analysis. Ten healthy subjects (aged 31+/-2 years) in supine and sitting positions were evaluated after the administration of bromocriptine (2.5 mg) alone and after pharmacological peripheral D(2)-like blockade by domperidone (20 mg). We calculated (autoregressive method) the following: the low-frequency (LF) component (an index of cardiac sympathetic tone), the high-frequency (HF) component (an index of cardiac vagal tone), and the LF/HF ratio (an index of cardiac sympathovagal balance). With subjects in the supine position, bromocriptine alone induced a significant increase in the LF component and the LF/HF ratio, together with a reduction in norepinephrine plasma levels and blood pressure values. These conflicting effects can be explained as the combined result of direct and indirect (reflex-mediated) actions of bromocriptine in vivo. No changes in cardiac autonomic drive were observed with subjects in the sitting position. After domperidone pretreatment, bromocriptine induced a reduction in the LF component and in the LF/HF ratio. The sitting position caused an increase in heart rate and in the LF/HF ratio. We demonstrated both peripheral and central effects of bromocriptine. In particular, pretreatment with a peripheral antagonist (domperidone) allowed us to unmask the central effect of bromocriptine on cardiac sympathetic drive.

Adult↗