Biomedical subjects

S Martelli

Publications and source records attributed to S Martelli.

At least 19 recordsLinked to original sources

PubMed2006

New intraoperative protocol for kinematic evaluation of ACL reconstruction: preliminary results.

A real improvement in anterior cruciate ligament (ACL) surgery would be achieved if a global kinematic evaluation of graft performance could be made during surgery. A quantitative evaluation of all residual instabilities would be helpful in the evaluation of graft performances. This paper describes a new protocol for an accurate and extensive computer-assisted in vivo evaluation of joint laxities during ACL reconstruction. Fifteen in vivo kinematic evaluations during ACL reconstruction were performed using an optical localizer and custom software. The capability of the protocol was studied by analyzing the accuracy and repeatability of the results, the ergonomics of the setup, time taken, interactions with the surgical steps, and efficacy of the acquisitions. Repeatability of the tests, at maximum force, remained under 1 mm/2 degrees . Repeatability in tibia position and orientation was lower than 1 mm/4 degrees . Secondary laxities during stress tests remained under 2 mm/3 degrees . Added time to surgery was about 11 min. ACL graft increased joint stability up to 52% with respect to the preoperative level. The simplicity and morbidity of the test procedure and system was minimally invasive and allowed a quantitative evaluation of knee laxities at time zero. The repeatability of the tests opens the way for future research on in vivo evaluation of different ACL reconstruction techniques, which may lead to a better understanding of associated lesions and their role to the global knee stability.

Adult↗

PubMed2006

Extracorporeal circulation with low systemic heparinization during lung transplantation.

BACKGROUND: Some lung transplantation (LT) recipients suffer from pulmonary hypertension and right ventricular dysfunction or failure requiring extracorporeal circulation (ECC) to avoid catastrophic complications during surgery. The extracorporeal support usually requires systemic heparinization which is potentially associated with important side effects. We performed eight LT using preheparinized ECC circuits and an oxygenator associated with a lower level of systemic heparinization without evidence of perioperative complications. PATIENTS AND METHODS: From May 2002 to May 2005, 8 patients (5 men and 3 women) of mean age 22.5 +/- 9.5 years underwent bilateral sequential lung transplantation (BSLT) for cystic fibrosis (n = 6) or idiopathic pulmonary fibrosis (n = 2). All procedures were performed with ECC through a femoro-femoral veno-arterial bypass with preheparinized circuits and an oxygenator. RESULTS: No intraoperative mortality occurred. The mean ECC time was 147.8 +/- 31.3 minutes and the mean heparin administered was 3525 +/- 969.16 UI. No coagulopathy or thrombotic events were observed perioperatively. CONCLUSIONS: Our study confirmed the efficacy and safety of prehepanized circuits and oxygenator for femoro-femoral veno-arterial bypass during LT for patients with severe pulmonary hypertension requiring ECC.

Adult↗

PubMed2005

Validation of a new protocol for computer-assisted evaluation of kinematics of double-bundle ACL reconstruction.

BACKGROUND: Computer-assisted surgery is useful to increase the precision of anterior cruciate ligament (ACL) surgical procedure, but could be even more important in evaluating the global performance of reconstructed ACL. This paper describes a new protocol for an accurate and extensive computer-assisted evaluation of single- and double-bundle reconstructions of ACL. METHODS: The protocol consists of the acquisition of the leg axes, ACL and graft insertions by a navigation system, and tracking of the knee motion during the classical kinematic test of knee stability. These data are elaborated by computer software in order to compute graft biomechanical behaviour and the knee kinematics and estimate the performance of the intervention. FINDINGS: The proposed protocol was validated on three cadaver knees. It resulted minimally invasive, effective to describe graft kinematic performance and able to provide a 3D reliable description of the reconstructed knee. INTERPRETATION: The protocol is an extension of the present evaluation of computer-assisted packages and includes additional kinematic tests and computations. The scientist-reader can find important details on tested computations to implement a similar computer-assisted procedure for new applications in knee surgery, while the surgeon can find in this procedure a means to improve the evaluation of ACL reconstruction and identify the residual laxity.

Anterior Cruciate Ligament↗

PubMed2005

Imaging knee position using MRI, RSA/CT and 3D digitisation.

The purpose of this study was to compare 3 methods of imaging knee position. Three fresh cadaver knees were imaged at 6 flexion angles between 0 degrees and 120 degrees by MRI, a combination of RSA and CT and 3D digitisation (in two knees). Virtual models of all 42 positions were created using suitable computer software. Each virtual model was aligned to a newly defined anatomically based Cartesian coordinate system. The angular rotations around the 3 coordinate system axes were calculated directly from the aligned virtual models using rigid body kinematics and found to be equally accurate for the 3 methods. The 3 rotations in each knee could be depicted using anatomy-based diagrams for all 3 methods. We conclude that the 3 methods of data acquisition are equally and adequately accurate in vitro. MRI may be the most useful in vivo.

Cadaver↗

PubMed2004

Computer investigation of ACL orientation during passive range of motion.

No quantitative data are reported in the literature regarding the orientation of anterior cruciate ligament (ACL) fibers during passive range of motion. In this study we performed an original qualitative and quantitative analysis in eight cadaver knees, examining ACL elongation and 3D orientation. Computer elaboration of anatomical and kinematic data obtained by a six degrees-of-freedom electrogoniometer enabled a mathematical and statistical evaluation of the 3D behavior of the ACL. Our data confirmed the isometric behavior of ACL. The inclination of ACL with respect to the tibial plateau decreases with flexion from 56 degrees to 33 degrees. Orientation of ACL with respect to the femoral notch increases with flexion from 4 degrees to 58 degrees. The ACL orientation in a medio-lateral direction changes from 24 degrees to 52 degrees. The postero-lateral and the antero-medial bundle have different angular variations, mainly with respect to the tibial plateau and medio-lateral direction. This quantitative and qualitative information not only increases the anatomical knowledge of the ACL, but could also be important in developing or improving the surgical strategy for ACL reconstruction.

Anterior Cruciate Ligament↗

PubMed2004

In vivo evaluation of a computer planning system for total knee arthroplasty.

In this paper we report the analysis of a preoperative computer planner for total knee arthroplasty (TKA), when applied to a set of patients by different surgeons. The goal of this work was to study the repeatability and reliability of computer planning, the ergonomy of the system, identify the useful features of this technique and the possible drawbacks. The planning system allows the surgeon to interactively stimulate the implant on a 3D model of the patient computed from computerized tomography (CT) images. In this paper, we summarize the main results of a series of evaluation trials carried out by four surgeons on ten patients. We measured the variability of the main application parameters, evaluated the efficacy and usefulness of the automatic prosthesis positioning provided by the system and carefully analyzed the system ergonomy. The system showed satisfactory repeatability in the interactive definition of the essential parameters. Moreover it showed to be easy to use, consistent, focused on the most important parameters and able to improve the surgeon's insight and confidence in the outcome. Further steps include clinical studies and direct comparison with standard technique.

Arthroplasty, Replacement, Knee↗

PubMed2003

How well are hypertension and albuminuria treated in type II diabetic patients?

The purpose of this study was to assess the management of both hypertension and micro/macroalbuminuria in a cohort of type II diabetic patients. In the first 6 months of the year 2000, 5815 diabetic patients were identified through prescriptions for antidiabetic drugs in our sanitary district (191 568 inhabitants). In all, 65% (3810) of these type II diabetic patients were also given prescriptions for antihypertensive drugs. A total of 400 diabetic patients were randomly selected and 171 entered the study (gender: 94/77 M/F; age: 66.6+/-8 years; diabetes duration: 12+/-9 years): 100 patients (group DT) were treated with antihypertensive drugs and 71 (group DU) were untreated. Blood pressure, urine albumin-to-creatinine ratio (ACR), and glycated haemoglobin were measured in the two groups. A total of 80% (57/71) of DU patients were hypertensive (BP>/=130/85 mmHg). Specifically, 24.4% had diastolic hypertension (BP>/=85 mmHg) and 79% systolic hypertension (BP>/=130 mmHg). Only 63% (100/157) of the hypertensive patients were treated with antihypertensive drugs (two drugs/patient on average, range 1-5). In addition, only 13% of the DT patients were adequately controlled (BP<130/85 mmHg), while the others had above target blood pressure levels (14%: 130-139/85-89 mmHg; 40%: 140-159/90-95 mmHg, and 33%>/=160/95 mmHg). Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) were included in the antihypertensive medical regimen in 70% of the DT patients (ACE-I: 62%; ARB: 8%; diuretics: 39%; dihydropyridine calcium antagonists: 38%; alpha-blockers: 20%, beta-blockers: 17%; clonidin: 8%; nondihydropyridine calcium antagonists: 5%). Only 33% of type II diabetic patients underwent a screening for microalbuminuria as assessed on clinical records. The same percentage of micro- and macroalbuminuric patients (13.5%) was observed in the DT group, whereas 25% micro vs 3% macro were found in the DU group. In all, 73% of microalbuminuric patients were not on ACE-I/ARB. Hypertensive type II diabetic patients were often left untreated and only a minority of those treated were optimally controlled. The importance of an elevated systolic pressure is underestimated and the number of antihypertensive drugs prescribed insufficient. Screening and treatment of albuminuria are inadequate.

Aged↗

PubMed2002

Anthrapyridones, a novel group of antitumour non-cross resistant anthraquinone analogues. Synthesis and molecular basis of the cytotoxic activity towards K562/DOX cells.

1. Multidrug resistance (MDR) to antitumour agents, structurally dissimilar and having different intracellular targets, is the major problem in cancer therapy. MDR phenomenon is associated with the presence of membrane proteins which belong to the ATP-binding cassette family transporters responsible for the active drug efflux leading to the decreased intracellular accumulation. 2. The search of new compounds able to overcome MDR is of prime importance. 3. Recently we have synthesized a new family of anthrapyridone compounds. The series contained derivatives modified with appropriate hydrophobic or hydrophylic substituents at the side chain. 4. The interaction of these derivatives with erythroleukemia K562 sensitive and K562/DOX resistant (overexpressing P-glycoprotein) cell lines has been examined. The study was performed using a spectrofluorometric method which allows to continuously follow the uptake and efflux of fluorescent molecules by living cells. 5. It was demonstrated that the increase in the lipophilicity of anthrapyridones favoured the very fast cellular uptake exceeding the rate of P-gp dependent efflux out of the cell. For these derivatives, very high accumulation (the same for sensitive and resistant cells) was observed and the in vitro biological data confirmed that these compounds exhibited comparable cytotoxic activity towards sensitive and P-gp resistant cell line. In contrast, anthrapyridones modified with hydrophylic substituents exhibited relatively low kinetics of cellular uptake. 6. For these derivatives decreased accumulation in resistant cells was observed and the in vitro biological data demonstrated that they were much less active against P-gp resistant cells in comparison to sensitive cells. 7. We also studied, using confocal microscopy, the intracellular distribution of anthrapyridones in NIH-3T3 cells. Our data showed that these compounds were strongly accumulated in the nucleus and lysosomes.

3T3 Cells↗

PubMed2002

Comparison of three kinematic analyses of the knee: determination of intrinsic features and applicability to intraoperative procedures.

The evaluation of knee motion is an important step for correct diagnoses and optimal surgical reconstructions, but controversial opinions still remain about the most suitable numerical method for the elaboration of clinical kinematic tests. In this paper, we present a comparison of three methods applied to an experimental animal study (Grood and Suntay method [Grood, E.S. and Suntay, W.J. (1983) "A coordinate system for the clinical description of three-dimensional motions: application to the knee", J. Biomech. Engng, 105, pp. 136-144], Helical Axes method [Blankevoort, L., Huiskes, R. and de Lange, A. (1990). "Helical axes of passive knee joint motions", J. Biomech., 23 pp. 1219-1229] and Functional method [Martelli, S., Zaffagnini, S., Falcioni, B. and Marcacci, M. (2000). "Intraoperative kinematic protocol for knee joint evaluation", Comput. Methods Programs Biomed., 62 pp. 77-86]). The study shows the numerical differences among the three protocols and evaluates their performances and repeatability during clinical tests, i.e. laxity measurements and passive range of motion. The Functional method gives the optimal compromise among accuracy, clinical interpretability and ease of use for intraoperative kinematic evaluations.

Animals↗

PubMed2002

The shapes of the tibial and femoral articular surfaces in relation to tibiofemoral movement.

We report a study of the shapes of the tibial and femoral articular surfaces in sagittal, frontal and coronal planes which was performed on cadaver knees using two techniques, MRI and computer interpolation of sections of the articular surfaces acquired by a three-dimensional digitiser. The findings using MRI, confirmed in a previous study by dissection, were the same as those using the digitiser. Thus both methods appear to be valid anatomical tools. The tibial and femoral articular surfaces can be divided into anterior segments, contacting from 0 degrees to 20 +/- 10 degrees of flexion, and posterior segments, contacting from 20 +/- 10 degrees to 120 degrees of flexion. The medial and lateral compartments are asymmetrical, particularly anteriorly. Posteromedially, the femur is spherical and is located in a conforming, but partly deficient, tibial socket. Posterolaterally, it is circular only in the sagittal section and the tibia is flat centrally, sloping downwards both anteriorly and posteriorly to receive the meniscal horns. Anteromedially, the femur is convex with a sagittal radius larger than that posteriorly, while the tibia is flat sloping upwards and forwards. Anterolaterally, both the femoral and tibial surfaces are largely deficient. These shapes suggest that medially the femur can rotate on the tibia through three axes intersecting in the middle of the femoral sphere, but that the sphere can only translate anteroposteriorly and even then to a limited extent. Laterally, the femur can freely translate anteroposteriorly, but can only rotate around a transverse axis for that part of the arc, i.e., near extension, during which it comes into contact with the tibia through its flattened distal/medial surface as against its spherical posterior surface.

Femur↗

PubMed2001

Synthesis, antitumor cytotoxicity, and DNA-binding of novel N-5,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides.

A series of DNA-binding potential antitumor agents bearing a cationic carboxamide side chain attached in position peri to an electron-withdrawing atom, N-5,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides, has been prepared by reaction of the appropriate 1-chloro-9-oxo-9,10-dihydro-4-acridinecarboxamides with the suitable (omega-aminoalkyl)hydrazine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma cell line (HT29) is described and compared to that of reference drugs. Structure-activity relationships are discussed. Two highly DNA-affinic and potent cytotoxic compounds, 4m,o, have been identified as new leads in the antitumor strategies.

Acridines↗

PubMed2001

The spray drying of acetazolamide as method to modify crystal properties and to improve compression behaviour.

Acetazolamide shows a very poor compression ability and tablets must usually be produced through a wet granulation process. However, the possibility to obtain pure acetazolamide for direct compression could be interesting for industrial application. With the scope to obtain a material for direct compression, three different crystallisation methods were chosen, with respect to acetazolamide solvent solubility. (a) Acetazolamide was dissolved in an ammonia solution and then spray dried. It was possible to characterise the spherical particles as a mixture of two polymorphic forms, I and II by Powder X-ray diffraction study. (b) Pure form I was obtained by slowly cooling to room temperature a boiling water solution. (c) Pure form II, the marketed form, was obtained by neutralisation of an ammonia solution. Their compression behaviour was investigated firstly by a rotary press. Whilst pure polymorphic forms I and II could not be compressed, the spray dried particles showed very good compression properties. In fact, tablets were obtained only by spray dried particles, which show very good properties under compression and the absence of capping tendency. On the other hand, it was impossible to obtain tablets from polymorphic forms I and II, whatever compression pressures were used. In order to explain their densification mechanism, a single-punch tablet machine, equipped for the measurement of the upper punch displacement in the die, was used. From calculated Heckel's parameters, it was demonstrated that the spray dried material shows a greater particle rearrangement in the initial stage of compression due to its spherical habit and minor wrinkledness of particle surface. The crystalline structure due to the presence of polymorphic forms I and II concur to lowering the intrinsic elasticity of the material. This fact avoids the risk of the rupturing the interpaticulate bonds, which are formed during the compression, concurring to the consolidation of the tablet.

Acetazolamide↗

PubMed2001

Physical characterization of naproxen sodium hydrate and anhydrate forms.

Naproxen sodium (NS) is a nonsteroidal anti-inflammatory drug used in painful and inflammatory diseases. By crystallization from water or by exposure to relative humidities over 43%, the anhydrate form can be hydrated to a dihydrate species. Different techniques have been used to characterize physically anhydrate naproxen sodium (ANS) and hydrate naproxen sodium (HNS): elemental analysis, atomic absorption, electron scanning microscopy, thermomicroscopy, differential scanning calorimetry, Karl Fisher's titrimetry, thermogravimetry, spectrophotometric analysis and X-ray diffraction study. The hydration/dehydration mechanism, at different relative humidities, was investigated to evaluate their physical stability. When stored up to 43% relative humidity, ANS shows a good stability, whereas with an increase in relative humidity it is hydrated. HNS equilibrium solubility was determined at different temperatures (21, 26, 31, and 37 degrees C). Due to the metastability and the quick phase changes in the water of ANS, its solubility was calculated from intrinsic dissolution measurements at the same temperatures, as solubility measurements of HNS. Water solubility of ANS is greater than HNS, but the solubility difference decreases when the temperature decreases. This is due to the fact that at higher temperatures the intrinsic dissolution rates (IDR) of ANS are considerably faster and decrease as the temperature falls.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Spray-drying as a method for microparticulate controlled release systems preparation: advantages and limits. I. Water-soluble drugs.

Spray-drying was used for the preparation of paracetamol/eudragit RS or RL or ethylcellulose microspheres to verify the possibility of their use in controlled-release solid-dosage forms formulation and try to determine advantages and limits of the technique of such use. Microspheres were first characterized by scanning electron microscopy, differential scanning calorimetry, x-ray diffractometry, and in vitro dissolution studies and then used for the preparation of tablets. During this step, the compressibility of the spray-dried powders was also evaluated. In vitro dissolution studies were performed also on the tablets and their release control was accessed. Although powders were unable to slow down drug release, tablets obtained from microsphere compression showed a good capability of controlling paracetamol release when eudragit RS or ethylcellulose was used, even at low polymer amounts.

Acetaminophen↗

PubMed2001

Determination of an optimal kinematic protocol for computer-assisted evaluation of anterior cruciate ligament deficiency.

The recent development of computer-assisted techniques for surgery, anterior cruciate ligament (ACL) reconstruction in particular, provides new ways of improving intraoperative kinematic evaluation and final functional outcome. In this paper we have tried to identify the optimal protocol for ACL evaluation, which can fully exploit the novel capability of electronic sensors and computer elaboration. In this work we statistically compared the main clinical tests that are used for knee evaluation and three different numerical methods for kinematic analysis. Results showed that only passive tests that investigate rotational and anteroposterior stability could discriminate ACL status and that the most effective protocol for computerized evaluation should be based on the Lachman and Drawer test, and forced internal-external rotations at full extension for pigs and 60 degrees, elaborated with the functional method (Martelli et al. Comput. Methods Programs Biomed. 62:77-86, 2000).

Algorithms↗

PubMed2000

N4-(omega-Aminoalkyl)-1-[(omega-aminoalkyl)amino]-4- acridinecarboxamides: novel, potent, cytotoxic, and DNA-binding agents.

A series of DNA-binding potential antitumor agents, (omega-aminoalkyl)-4-acridinecarboxamides, has been prepared either by reduction of the corresponding (omega-aminoalkyl)-9-oxo-9, 10-dihydro-4-acridinecarboxamides with aluminum amalgam or by aminolysis of the corresponding (omega-aminoalkyl)-1-chloro-4-acridinecarboxamides with the suitable amine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potencies of these derivatives toward six tumor cell lines, including human colon adenocarcinoma (HT29) and human ovarian carcinoma (A2780-sensitive, A2780cisR cisplatin-resistant, CH1-sensitive, CH1cisR cisplatin-resistant, and SKOV-3) cells, are described and compared to that of reference drugs. One highly DNA affinic analogue (3a) has been identified with a useful broad spectrum of cytotoxic activity in the 4-7 nM range (mean IC(50) of 6 nM).

Acridines↗

PubMed2000

Intraoperative kinematic protocol for knee joint evaluation.

Although knee kinematics has been investigated widely, no standard, objective evaluation of the kinematics behaviour of the joint is used at present during surgical treatment. We propose a kinematic protocol for a manual intraoperative evaluation of the knee behaviour, with which the range of motion, the 'screw-home' mechanism and knee instabilities could be quantified. The method does not require anatomical landmarks, because it is computed from standard tests used in clinical practice and gives a decomposition of the knee movement comparable to the well known Grood and Suntay analysis [E.S. Grood, W.J. Suntay, A joint coordinate system for the clinical description of three-dimensional motions: application to the knee, J. Biomech. Eng. 105 (1983) 136-144]. We describe the protocol, report the evaluation of its numerical features and provide a comparison with Grood and Suntay method on ten porcine knees.

Animals↗

PubMed2000

Emulsion/solvent evaporation as an alternative technique in pellet preparation.

Paracetamol/Eudragit RS, paracetamol/ethylcellulose, and paracetamol/cellulose acetate pellets of different drug/polymer ratios (w/w) were prepared by the dissolution/solvent evaporation technique. These pellets were then characterized by particle size distribution analysis, ultraviolet (UV) spectroscopy, differential thermal analysis, and scanning electron microscopy (SEM). Hard gelatin capsules were filled with each particle size fraction of these pellets, and in vitro dissolution studies were performed to verify the capability of each series of pellets to control drug release. Pellets were spherical, presented a polynucleated microcapsule structure, and under certain experimental conditions, the yield of the preparation process reached very high values. The dissolution studies pointed out the slow paracetamol release from these pellets.

Acetaminophen↗