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Biomedical subjects

M Rambaldi

Publications and source records attributed to M Rambaldi.

At least 19 recordsLinked to original sources
PubMed2005

Effectiveness and safety of carotid endarterectomy under remifentanil.

AIM: The aim of this study was to evaluate the effectiveness and safety of carotid endarterectomy (CEA) with conscious sedation under remifentanil (Remifentanil anesthesia - RA) vs conventional loco-regional anesthesia (Conventional-LRA) in the current practice of a vascular surgery unit. METHODS: We introduced the ''Remifentanil-RA'' in our practice according to a two-step protocol. In the first step we performed a pilot prospective study to assess the procedure's safety and reproducibility in our setting on 60 consecutive patients with symptomatic and/or high-grade (>70%) internal carotid artery stenosis and alternately assigning them either to ''Remifentanil-RA'' or ''Conventional-LRA'' CEA. In the second step we analysed our routine operative records as to effectiveness and safety on 533 patients who consecutively underwent ''Remifentanil-RA'' CEA. We compared them with 533 age- and sex-matched historical controls who underwent ''Conventional-LRA'' CEA. RESULTS: The patients' mean age was 71.2+/-6.8 vs 71.8+/-6.1 (''Remifentanil-RA'' vs ''Conventional-LRA''). About 73% of them were male and 56% had a symptomatic carotid stenosis. Neither the pilot study nor second step comparison showed differences in outcome measures. We found only higher peri-operative nausea/ vomit (3.6% vs 0.4% ''Remifentanil-RA'' vs ''Conventional-LRA'', P<0.0002) and fewer re-operations for post-operative hematomas (3% vs 5.4% respectively, P=0.048). CONCLUSIONS: We found that ''Remifentanil-RA'' CEA was safe, effective and satisfactory. Nevertheless, with the potential problems of intubation and those already found with side effects, a randomized control trial (RCT) is needed in order to prove that this method is superior to ''Conventional-LRA'' CEA.

Aged↗
PubMed2001

Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.

The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.

Acetylcholinesterase↗
PubMed2001

Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles.

A number of selected imidazo[2,1-b]thiazoles entered the screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) and one of these compounds, 2-chloro-6-phenylimidazo[2,1-b]thiazole, showed antitubercular activity. On this basis we planned the synthesis of new analogues bearing a substituted ring at the 6 position. For one compound only (2-chloro-6-p-chlorophenylimidazo[2,1-b]thiazole) the 5-nitroso derivative was also prepared. The antitubercular activity of these compounds was compared with the known analogues lacking the chlorine at the 2 position. 5-Nitroso-6-p-chlorophenylimidazo[2,1-b]thiazole showed potent antitubercular activity.

Antitubercular Agents↗
PubMed2000

4-Aminopyridine derivatives with antiamnesic activity.

Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.

4-Aminopyridine↗
PubMed2000

Potential antitumor agents. Part 29(1): synthesis and potential coanthracyclinic activity of imidazo[2,1-b]thiazole guanylhydrazones.

This paper reports the synthesis of new imidazo[2,1-b]thiazole guanylhydrazones which were tested as potential antitumor agents. Three of these derivatives (those bearing a 3- or 4-nitrophenyl group) were the most potent and one of these showed a mild effect as CDK1 inhibitor. These same three derivatives were also tested as positive inotropic agents and two of them were more potent than amrinone at 10(-5) M. These two guanylhydrazones could be useful coanthracyclinic agents.

Animals↗
PubMed2000

Imidazo[2,1 -b]thiazolylmethylene- and indolylmethylene-2-indolinones: a new class of cyclin-dependent kinase inhibitors. Design, synthesis, and CDK1/cyclin B inhibition.

Compounds containing a 2-indolinone moiety linked to imidazothiazole and indole fragments were studied as cyclin-dependent kinase inhibitors. The activity of all the new derivatives was tested in vitro against CDK1/cyclinB and the selectivity towards two other kinases was determined for the most promising compounds. The binding mode of one representative compound was investigated by means of a three-dimensional model of the inhibitor-CDK1 complex. The work allowed us to identify (2-chloroindolyl)methylene-2-indolinone as a new lead of a class of CDK1/cyclinB inhibitors, whose potency can be improved by the introduction of suitable variations on the basic molecular skeleton.

Binding Sites↗
PubMed1999

Ischaemic necrotizing pancreatitis after cardiac surgery. A case report and review of the literature.

Ischaemia is a rare but often lethal aetiology of pancreatitis. A 67-year-old man underwent aortocoronary by-pass. Postoperatively, he developed atrial fibrillation and possibly acute myocardial infarction. Later, he had acute pancreatitis and underwent laparotomy for purulent peritonitis due to a ruptured pancreatic abscess. Cholesterolosis was found but no gallstones. The postoperative period was heavily complicated and the patient eventually died due to multiorgan failure. The occurrence of ischaemic pancreatitis should be more readily suspected in patients with abdominal symptoms following surgery that induces ischaemia of the pancreas. It is possible that delay in diagnosis accounts for the high death rate of such postoperative complication.

Aged↗
PubMed1998

Infective endocarditis presenting as polyarthritis.

We report the case of a patient who complained of arthralgias and arthritis 1 month before the onset of fever or other signs of infective endocarditis. In 2 months she developed an additive, asymmetrical polyarthritis with fever (febrile polyarthritis). Splenomegaly was present. Two-dimensional echocardiography showed no vegetations or other findings suggesting endocardial involvement. Initially, four blood cultures showed no microorganisms, then six of nine subsequent blood cultures grew highly gentamicin-resistant Enterococcus faecalis.

Adult↗
PubMed1998

An unusual case of primary systemic amyloidosis.

Here we report an unusual case of primary systemic amyloidosis. The cutaneous lesions were polymorphic and included involvement of both external auditory canals. The visceral involvement was covert. Mapping of amyloid deposits was performed using scintigraphy with technetium-99m (V) dimercaptosuccinic acid ([99mTc (V)] DMSA). Therapy with melphalan, prednisone and colchicine resulted in considerable improvement.

Aged↗
PubMed1997

Expression of teratocarcinoma-derived growth factor-1 (TDGF-1) in testis germ cell tumors and its effects on growth and differentiation of embryonal carcinoma cell line NTERA2/D1.

The teratocarcinoma-derived growth factor-1 (TDGF-1) gene codes for a 188-aminoacid glycoprotein that shares structural homology with the epidermal growth factor (EGF) family of growth factors. TDGF-1 is highly expressed in the undifferentiated embryonal carcinoma stem cell line NTERA2 clone D1 (NT2/D1) and its expression is downregulated in response to differentiating agents such as retinoic acid (RA) and hexamethylen-bisacetamide (HMBA). To assess the role of TDGF-1 in the onset and/or progression of human germ cell tumors, we analysed TDGF-1 expression by Northern blot and immunostaining in a panel of 59 human germ cell tumors of different histological origins. We show that TDGF-1 expression is markedly elevated in a subset of human testicular germ cell tumors as compared to normal testes. TDGF-1 overexpression occurs in about 100% of tumors with non-seminomatous phenotype, such as embryonal carcinomas and malignant undifferentiated teratocarcinomas. To address the questions of how TDGF-1 (previously called CRIPTO) may affect the growth and/or the differentiation of embryonal carcinoma cells, we have characterized the effects of exogenous recombinant TDGF-1 protein on the proliferation rate and differentiation 'potential of NT2/D1. Exogenous TDGF-1 protein stimulated DNA synthesis and cell proliferation in both undifferentiated and differentiated NT2/D1 cells. However, TDGF-1 protein treatment was unable to block differentiation induced by both RA and HMBA. These results suggest that TDGF-1 growth factor may represent an autocrine growth factor that may be involved in the process of development of testicular neoplasms.

Amino Acid Sequence↗
PubMed1996

Neovascularization in human germ cell tumors correlates with a marked increase in the expression of the vascular endothelial growth factor but not the placenta-derived growth factor.

Neoangiogenesis is a prerequisite for tumor growth and metastasis. In germ cell cancer patients with the disease limited to the testicle (stage A), tumor-associated neovascularization is predictive of metastatic disease (stage B). To investigate the molecular mechanisms underlying neovascularization in human germ cell tumors (GCTs), we analysed the expression of two angiogenic growth factors, vascular endothelial growth factor (VEGF) and placenta growth factor (P1GF), and of their receptors (FLT-1) and Flk-1/KDR) in a panel of testicular tumors. In this study we show a marked increase in VEGF expression in 36/44 (81.8%) primary testicular-derived GCTs, as compared to normal testis, that significantly correlates with a high density of intratumor microvessels (r = 0.72461, P < 0.001; n = 24). As determined by RT - PCR and/or Western blot, the predominant VEGF isoforms expressed in GCTs are the VEGF121 and VEGF165, which are more efficiently secreted by the cells, and thus more active in eliciting angiogenesis. Conversely, in the case of PIGF, only a weak correlation with the vascular density of tumors is observed (r = 0.26599, P < 0.05; n = 24). Northern blot analysis also revealed significant up-regulation of VEGF/ PIGF receptors in highly vascularized germ cell tumors, compared to normal testes. These findings suggest that VEGF may act in a paracrine manner to induce neovascularization, oedema extravasation and cyst formation in human germ cell tumors. The correlation between VEGF expression and the vascular density of tumors, suggest that the evaluation of VEGF expression may be of help in predicting patients at risk for metastatic diseases. Finally, we demonstrate that VEGF up-regulation may occur at the RNA level since no gene amplification is observed; conversely, in in vitro models such as the embryonal stem cell line NTERA-2 and the choricarcinoma JEG-3 cell line, VEGF (but not PIGF) mRNA expression is regulated by hypoxic stress.

Base Sequence↗
PubMed1996

Potential antitumor agents. 24. Synthesis and pharmacological behavior of imidazo[2,1-b]thiazole guanylhydrazones bearing at least one chlorine.

In connection with a previous research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other hand, the most active cardiotonic agents were devoid of the phenyl ring.

Animals↗
PubMed1996

Immunoscintigraphy as an adjunct to diagnostic imaging in septic sacroiliitis. Report of a case.

Septic sacroiliitis in childhood is a relatively rare condition. We describe a case of septic sacroiliitis occurring in an 11-year-old girl in whom the diagnosis was suspected on clinical findings and bone scan. Immunoscintigraphy with 99mTc-labelled antigranulocyte antibodies further supported the hypothesis for a septic origin of the disease. The clinical evolution clinched the diagnosis.

Anti-Bacterial Agents↗
PubMed1996

Prevalence of alcohol problems in general practice: an experience from southern Italy.

The Michigan Alcoholism Screening Test (MAST) and the response to a question about heavy alcohol consumption were used to assess the prevalence of alcohol problems in consecutive patients (77 males and 46 females) consulting a general practitioner in an urban area in the South of Italy (Castellammare di Stabia). Alcohol problems, which were defined by a cut-off score of 5 on the MAST and/or by heavy alcohol consumption (corresponding to at least 60 g of ethanol daily for males and 36 g of ethanol daily for females for at least 2 years), were identified in 54 patients [43.9%; 95% confidence interval (CI) 35.0-53.1%], 45 males (58.4%; 95% CI 46.6-69.6%) and nine females (19.6%; 95% CI 9.4-33.9%). The prevalence of MAST positive patients was 32.5% (95% CI 24.4-41.6%) in the total patient sample, 45.5% (95% CI 34.1-57.2%) among males and 10.9% (95% CI 3.6-23.6%) among females. The question about heavy alcohol consumption had a predictive negative value of 97.2% (95% CI 90.2-99.7%) and a predictive positive value of 73.1% (95% CI 59.0-84.4%) in relation to MAST positive patients. It is suggested that general practitioners should incorporate this question about heavy alcohol consumption as a screening question in order to detect alcohol problems and give advice regarding reduction of alcohol consumption.

Adolescent↗
PubMed1995

Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines.

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.

Blotting, Western↗